Download PDF
Semin Respir Crit Care Med 2014; 35(02): 181-200
DOI: 10.1055/s-0034-1371527
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Biomarkers in Connective Tissue Disease-Associated Interstitial Lung Disease

Francesco Bonella
1   Department of Pneumology and Allergy, Ruhrlandklinik, University Hospital, University of Duisburg-Essen, Germany
,
Ulrich Costabel
1   Department of Pneumology and Allergy, Ruhrlandklinik, University Hospital, University of Duisburg-Essen, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
25 March 2014 (online)

    Permissions and Reprints

Abstract

This article reviews major biomarkers in serum and bronchoalveolar lavage fluid (BALF) with respect to their diagnostic and prognostic value in connective tissue disease–associated interstitial lung disease (CTD-ILD). In some CTD such as systemic sclerosis (SSc), the incidence of ILD is up to two-third of patients, and currently ILD represents the leading cause of death in SSc. Because of the extremely variable incidence and outcome of ILD in CTD, progress in the discovery and validation of biomarkers for diagnosis, prognosis, patients' subtyping, response to treatment, or as surrogate endpoints in clinical trials is extremely important. In contrast to idiopathic interstitial pneumonias, autoantibodies play a crucial role as biomarkers in CTD-ILD because their presence is strictly linked to the pathogenesis and tissue damage. Patterns of autoantibodies, for instance, anticitrullinated peptide antibodies in rheumatoid arthritis or aminoacyl-tRNA synthetases (ARS) in polymyositis/dermatomyositis, have been found to correlate with the presence and occasionally with the course of ILD in CTD. Besides autoantibodies, an increase in serum or BALF of a biomarker of pulmonary origin may be able to predict or reflect the development of fibrosis, the impairment of lung function, and ideally also the prognosis. Promising biomarkers are lung epithelium-derived proteins such as KL-6 (Krebs von den Lungen-6), SP-D (surfactant protein-D), SP-A (surfactant protein-A), YKL-40 (chitinase-3-like protein 1 [CHI3L1] or cytokines such as CCL18 [chemokine (C-C) motif ligand 18]). In the future, genetic/epigenetic markers, such as human leukocyte antigen (HLA) haplotypes, single nucleotide polymorphisms, and micro-RNA, may help to identify subtypes of patients with different needs of management and treatment strategies.

Keywords

connective tissue disease - biomarkers - interstitial lung disease
 

  • References

  • 1 Olson AL, Brown KK, Fischer A. Connective tissue disease-associated lung disease. Immunol Allergy Clin North Am 2012; 32 (4) 513-536
    CrossrefPubMedGoogle Scholar
  • 2 Launay D, Remy-Jardin M, Michon-Pasturel U , et al. High resolution computed tomography in fibrosing alveolitis associated with systemic sclerosis. J Rheumatol 2006; 33 (9) 1789-1801
    PubMedGoogle Scholar
  • 3 Vij R, Strek ME. Diagnosis and treatment of connective tissue disease-associated interstitial lung disease. Chest 2013; 143 (3) 814-824
    CrossrefPubMedGoogle Scholar
  • 4 Gutsche M, Rosen GD, Swigris JJ. Connective tissue disease-associated interstitial lung disease: a review. Curr Respir Care Rep 2012; 1: 224-232
    CrossrefPubMedGoogle Scholar
  • 5 Fischer A, du Bois R. Interstitial lung disease in connective tissue disorders. Lancet 2012; 380 (9842) 689-698
    CrossrefPubMedGoogle Scholar
  • 6 Steen VD, Medsger TA. Changes in causes of death in systemic sclerosis, 1972-2002. Ann Rheum Dis 2007; 66 (7) 940-944
    CrossrefPubMedGoogle Scholar
  • 7 Tyndall AJ, Bannert B, Vonk M , et al. Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database. Ann Rheum Dis 2010; 69 (10) 1809-1815
    CrossrefPubMedGoogle Scholar
  • 8 Olson AL, Swigris JJ, Sprunger DB , et al. Rheumatoid arthritis-interstitial lung disease-associated mortality. Am J Respir Crit Care Med 2011; 183 (3) 372-378
    CrossrefPubMedGoogle Scholar
  • 9 Vij R, Noth I, Strek ME. Autoimmune-featured interstitial lung disease: a distinct entity. Chest 2011; 140 (5) 1292-1299
    CrossrefPubMedGoogle Scholar
  • 10 Mittoo S, Gelber AC, Christopher-Stine L, Horton MR, Lechtzin N, Danoff SK. Ascertainment of collagen vascular disease in patients presenting with interstitial lung disease. Respir Med 2009; 103 (8) 1152-1158
    CrossrefPubMedGoogle Scholar
  • 11 Centola M, Cavet G, Shen Y , et al. Development of a multi-biomarker disease activity test for rheumatoid arthritis. PLoS ONE 2013; 8 (4) e60635
    CrossrefPubMedGoogle Scholar
  • 12 Hirata S, Dirven L, Shen Y , et al. A multi-biomarker score measures rheumatoid arthritis disease activity in the BeSt study. Rheumatology (Oxford) 2013; 52 (7) 1202-1207
    CrossrefPubMedGoogle Scholar
  • 13 Lota HK, Renzoni EA. Circulating biomarkers of interstitial lung disease in systemic sclerosis. Int J Rheumatol 2012; 2012: 121439
    PubMedGoogle Scholar
  • 14 Takemoto Y, Sakatani M, Takami S , et al. Association between angiotensin II receptor gene polymorphism and serum angiotensin converting enzyme (SACE) activity in patients with sarcoidosis. Thorax 1998; 53 (6) 459-462
    CrossrefPubMedGoogle Scholar
  • 15 Seibold MA, Wise AL, Speer MC , et al. A common MUC5B promoter polymorphism and pulmonary fibrosis. N Engl J Med 2011; 364 (16) 1503-1512
    CrossrefPubMedGoogle Scholar
  • 16 Ishikawa N, Hattori N, Yokoyama A, Kohno N. Utility of KL-6/MUC1 in the clinical management of interstitial lung diseases. Respir Investig 2012; 50 (1) 3-13
    PubMedGoogle Scholar
  • 17 Horimasu Y, Hattori N, Ishikawa N , et al. Different MUC1 gene polymorphisms in German and Japanese ethnicities affect serum KL-6 levels. Respir Med 2012; 106 (12) 1756-1764
    CrossrefPubMedGoogle Scholar
  • 18 Papiris SA, Kagouridis K, Bouros D. Serologic evaluation in idiopathic interstitial pneumonias. Curr Opin Pulm Med 2012; 18 (5) 433-440
    CrossrefPubMedGoogle Scholar
  • 19 Self SE. Autoantibody testing for autoimmune disease. Clin Chest Med 2010; 31 (3) 415-422
    CrossrefPubMedGoogle Scholar
  • 20 Corte TJ, Copley SJ, Desai SR , et al. Significance of connective tissue disease features in idiopathic interstitial pneumonia. Eur Respir J 2012; 39 (3) 661-668
    CrossrefPubMedGoogle Scholar
  • 21 Nagai S, Handa T, Tabuena R, Kitaichi M, Izumi T. Nonspecific interstitial pneumonia: a real clinical entity?. Clin Chest Med 2004; 25 (4) 705-715 , vi
    CrossrefPubMedGoogle Scholar
  • 22 Prasse A, Müller-Quernheim J. Non-invasive biomarkers in pulmonary fibrosis. Respirology 2009; 14 (6) 788-795
    CrossrefPubMedGoogle Scholar
  • 23 Lukacs NW, Hogaboam C, Chensue SW, Blease K, Kunkel SL. Type 1/type 2 cytokine paradigm and the progression of pulmonary fibrosis. Chest 2001; 120 (1, Suppl): 5S-8S
    CrossrefPubMedGoogle Scholar
  • 24 Ramos C, Montaño M, García-Alvarez J , et al. Fibroblasts from idiopathic pulmonary fibrosis and normal lungs differ in growth rate, apoptosis, and tissue inhibitor of metalloproteinases expression. Am J Respir Cell Mol Biol 2001; 24 (5) 591-598
    CrossrefPubMedGoogle Scholar
  • 25 Selman M, King TE, Pardo A ; American Thoracic Society; European Respiratory Society; American College of Chest Physicians. Idiopathic pulmonary fibrosis: prevailing and evolving hypotheses about its pathogenesis and implications for therapy. Ann Intern Med 2001; 134 (2) 136-151
    CrossrefPubMedGoogle Scholar
  • 26 Selman M, Pardo A. Idiopathic pulmonary fibrosis: an epithelial/fibroblastic cross-talk disorder. Respir Res 2002; 3: 3
    CrossrefPubMedGoogle Scholar
  • 27 Chapman HA. Disorders of lung matrix remodeling. J Clin Invest 2004; 113 (2) 148-157
    CrossrefPubMedGoogle Scholar
  • 28 Tzouvelekis A, Kouliatsis G, Anevlavis S, Bouros D. Serum biomarkers in interstitial lung diseases. Respir Res 2005; 6: 78
    CrossrefPubMedGoogle Scholar
  • 29 Hant FN, Ludwicka-Bradley A, Wang HJ , et al; Scleroderma Lung Study Research Group. Surfactant protein D and KL-6 as serum biomarkers of interstitial lung disease in patients with scleroderma. J Rheumatol 2009; 36 (4) 773-780
    CrossrefPubMedGoogle Scholar
  • 30 Assassi S, Sharif R, Lasky RE , et al; GENISOS Study Group. Predictors of interstitial lung disease in early systemic sclerosis: a prospective longitudinal study of the GENISOS cohort. Arthritis Res Ther 2010; 12 (5) R166
    CrossrefPubMedGoogle Scholar
  • 31 Murray LA, Rubinowitz A, Herzog EL. Interstitial lung disease: is interstitial lung disease the same as scleroderma lung disease?. Curr Opin Rheumatol 2012; 24 (6) 656-662
    CrossrefPubMedGoogle Scholar
  • 32 Baraut J, Michel L, Verrecchia F, Farge D. Relationship between cytokine profiles and clinical outcomes in patients with systemic sclerosis. Autoimmun Rev 2010; 10 (2) 65-73
    CrossrefPubMedGoogle Scholar
  • 33 Fertig N, Domsic RT, Rodriguez-Reyna T , et al. Anti-U11/U12 RNP antibodies in systemic sclerosis: a new serologic marker associated with pulmonary fibrosis. Arthritis Rheum 2009; 61 (7) 958-965
    CrossrefPubMedGoogle Scholar
  • 34 Okano Y, Steen VD, Medsger Jr TA. Autoantibody reactive with RNA polymerase III in systemic sclerosis. Ann Intern Med 1993; 119 (10) 1005-1013
    CrossrefPubMedGoogle Scholar
  • 35 Mihai C, Tervaert JW. Anti-endothelial cell antibodies in systemic sclerosis. Ann Rheum Dis 2010; 69 (2) 319-324
    CrossrefPubMedGoogle Scholar
  • 36 Hill MB, Phipps JL, Cartwright RJ, Milford Ward A, Greaves M, Hughes P. Antibodies to membranes of endothelial cells and fibroblasts in scleroderma. Clin Exp Immunol 1996; 106 (3) 491-497
    CrossrefPubMedGoogle Scholar
  • 37 Ihn H, Sato S, Fujimoto M , et al. Characterization of autoantibodies to endothelial cells in systemic sclerosis (SSc): association with pulmonary fibrosis. Clin Exp Immunol 2000; 119 (1) 203-209
    CrossrefPubMedGoogle Scholar
  • 38 Odani T, Yasuda S, Ota Y , et al. Up-regulated expression of HLA-DRB5 transcripts and high frequency of the HLA-DRB5*01:05 allele in scleroderma patients with interstitial lung disease. Rheumatology (Oxford) 2012; 51 (10) 1765-1774
    CrossrefPubMedGoogle Scholar
  • 39 Delgado-Vega A, Sánchez E, Löfgren S, Castillejo-López C, Alarcón-Riquelme ME. Recent findings on genetics of systemic autoimmune diseases. Curr Opin Immunol 2010; 22 (6) 698-705
    CrossrefPubMedGoogle Scholar
  • 40 Ohshimo S, Yokoyama A, Hattori N, Ishikawa N, Hirasawa Y, Kohno N. KL-6, a human MUC1 mucin, promotes proliferation and survival of lung fibroblasts. Biochem Biophys Res Commun 2005; 338 (4) 1845-1852
    CrossrefPubMedGoogle Scholar
  • 41 Seko A, Ohkura T, Ideo H, Yamashita K. Novel O-linked glycans containing 6′-sulfo-Gal/GalNAc of MUC1 secreted from human breast cancer YMB-S cells: possible carbohydrate epitopes of KL-6(MUC1) monoclonal antibody. Glycobiology 2012; 22 (2) 181-195
    CrossrefPubMedGoogle Scholar
  • 42 Yamane K, Ihn H, Kubo M , et al. Serum levels of KL-6 as a useful marker for evaluating pulmonary fibrosis in patients with systemic sclerosis. J Rheumatol 2000; 27 (4) 930-934
    PubMedGoogle Scholar
  • 43 Yanaba K, Hasegawa M, Hamaguchi Y, Fujimoto M, Takehara K, Sato S. Longitudinal analysis of serum KL-6 levels in patients with systemic sclerosis: association with the activity of pulmonary fibrosis. Clin Exp Rheumatol 2003; 21 (4) 429-436
    PubMedGoogle Scholar
  • 44 Yanaba K, Hasegawa M, Takehara K, Sato S. Comparative study of serum surfactant protein-D and KL-6 concentrations in patients with systemic sclerosis as markers for monitoring the activity of pulmonary fibrosis. J Rheumatol 2004; 31 (6) 1112-1120
    PubMedGoogle Scholar
  • 45 Bonella F, Volpe A, Caramaschi P , et al. Surfactant protein D and KL-6 serum levels in systemic sclerosis: correlation with lung and systemic involvement. Sarcoidosis Vasc Diffuse Lung Dis 2011; 28 (1) 27-33
    PubMedGoogle Scholar
  • 46 Doishita S, Inokuma S, Asashima H , et al. Serum KL-6 level as an indicator of active or inactive interstitial pneumonitis associated with connective tissue diseases. Intern Med 2011; 50 (23) 2889-2892
    CrossrefPubMedGoogle Scholar
  • 47 Janssen R, Kruit A, Grutters JC, Ruven HJ, Gerritsen WB, van den Bosch JM. The mucin-1 568 adenosine to guanine polymorphism influences serum Krebs von den Lungen-6 levels. Am J Respir Cell Mol Biol 2006; 34 (4) 496-499
    CrossrefPubMedGoogle Scholar
  • 48 Janssen R, Sato H, Grutters JC , et al. Study of Clara cell 16, KL-6, and surfactant protein-D in serum as disease markers in pulmonary sarcoidosis. Chest 2003; 124 (6) 2119-2125
    CrossrefPubMedGoogle Scholar
  • 49 Bernard A, Hermans C, Van Houte G. Transient increase of serum Clara cell protein (CC16) after exposure to smoke. Occup Environ Med 1997; 54 (1) 63-65
    CrossrefPubMedGoogle Scholar
  • 50 Petrek M, Hermans C, Kolek V, Fialová J, Bernard A. Clara cell protein (CC16) in serum and bronchoalveolar lavage fluid of subjects exposed to asbestos. Biomarkers 2002; 7 (1) 58-67
    CrossrefPubMedGoogle Scholar
  • 51 Hermans C, Petrek M, Kolek V , et al. Serum Clara cell protein (CC16), a marker of the integrity of the air-blood barrier in sarcoidosis. Eur Respir J 2001; 18 (3) 507-514
    CrossrefPubMedGoogle Scholar
  • 52 Kucejko W, Chyczewska E, Naumnik W, Ossolińska M. Concentration of surfactant protein D, Clara cell protein CC-16 and IL-10 in bronchoalveolar lavage (BAL) in patients with sarcoidosis, hypersensitivity pneumonitis and idiopathic pulmonary fibrosis. Folia Histochem Cytobiol 2009; 47 (2) 225-230
    PubMedGoogle Scholar
  • 53 Hasegawa M, Fujimoto M, Hamaguchi Y , et al. Use of serum Clara cell 16-kDa (CC16) levels as a potential indicator of active pulmonary fibrosis in systemic sclerosis. J Rheumatol 2011; 38 (5) 877-884
    CrossrefPubMedGoogle Scholar
  • 54 Pastva AM, Wright JR, Williams KL. Immunomodulatory roles of surfactant proteins A and D: implications in lung disease. Proc Am Thorac Soc 2007; 4 (3) 252-257
    CrossrefPubMedGoogle Scholar
  • 55 Takahashi H, Kuroki Y, Tanaka H , et al. Serum levels of surfactant proteins A and D are useful biomarkers for interstitial lung disease in patients with progressive systemic sclerosis. Am J Respir Crit Care Med 2000; 162 (1) 258-263
    CrossrefPubMedGoogle Scholar
  • 56 Asano Y, Ihn H, Yamane K , et al. Clinical significance of surfactant protein D as a serum marker for evaluating pulmonary fibrosis in patients with systemic sclerosis. Arthritis Rheum 2001; 44 (6) 1363-1369
    CrossrefPubMedGoogle Scholar
  • 57 Johansen JS. Studies on serum YKL-40 as a biomarker in diseases with inflammation, tissue remodelling, fibroses and cancer. Dan Med Bull 2006; 53 (2) 172-209
    PubMedGoogle Scholar
  • 58 Korthagen NM, van Moorsel CH, Barlo NP , et al. Serum and BALF YKL-40 levels are predictors of survival in idiopathic pulmonary fibrosis. Respir Med 2011; 105 (1) 106-113
    CrossrefPubMedGoogle Scholar
  • 59 Nordenbaek C, Johansen JS, Halberg P , et al. High serum levels of YKL-40 in patients with systemic sclerosis are associated with pulmonary involvement. Scand J Rheumatol 2005; 34 (4) 293-297
    CrossrefPubMedGoogle Scholar
  • 60 Prasse A, Pechkovsky DV, Toews GB , et al. CCL18 as an indicator of pulmonary fibrotic activity in idiopathic interstitial pneumonias and systemic sclerosis. Arthritis Rheum 2007; 56 (5) 1685-1693
    CrossrefPubMedGoogle Scholar
  • 61 Kodera M, Hasegawa M, Komura K, Yanaba K, Takehara K, Sato S. Serum pulmonary and activation-regulated chemokine/CCL18 levels in patients with systemic sclerosis: a sensitive indicator of active pulmonary fibrosis. Arthritis Rheum 2005; 52 (9) 2889-2896
    CrossrefPubMedGoogle Scholar
  • 62 Tiev KP, Hua-Huy T, Kettaneh A , et al. Serum CC chemokine ligand-18 predicts lung disease worsening in systemic sclerosis. Eur Respir J 2011; 38 (6) 1355-1360
    CrossrefPubMedGoogle Scholar
  • 63 Prasse A, Probst C, Bargagli E , et al. Serum CC-chemokine ligand 18 concentration predicts outcome in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2009; 179 (8) 717-723
    CrossrefPubMedGoogle Scholar
  • 64 Elhaj M, Charles J, Pedroza C , et al. Can serum surfactant protein D or CC-chemokine ligand 18 predict outcome of interstitial lung disease in patients with early systemic sclerosis?. J Rheumatol 2013; 40 (7) 1114-1120
    CrossrefPubMedGoogle Scholar
  • 65 Bonella F, Caramaschi P. The ambitious goal of validating prognostic biomarkers for systemic sclerosis-related interstitial lung disease. J Rheumatol 2013; 40 (7) 1034-1036
    CrossrefPubMedGoogle Scholar
  • 66 Carulli MT, Handler C, Coghlan JG, Black CM, Denton CP. Can CCL2 serum levels be used in risk stratification or to monitor treatment response in systemic sclerosis?. Ann Rheum Dis 2008; 67 (1) 105-109
    CrossrefPubMedGoogle Scholar
  • 67 Hasegawa M, Sato S, Takehara K. Augmented production of chemokines (monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1alpha (MIP-1alpha) and MIP-1beta) in patients with systemic sclerosis: MCP-1 and MIP-1alpha may be involved in the development of pulmonary fibrosis. Clin Exp Immunol 1999; 117 (1) 159-165
    CrossrefPubMedGoogle Scholar
  • 68 Antonelli A, Ferri C, Fallahi P , et al. CXCL10 (alpha) and CCL2 (beta) chemokines in systemic sclerosis—a longitudinal study. Rheumatology (Oxford) 2008; 47 (1) 45-49
    CrossrefPubMedGoogle Scholar
  • 69 Schmidt K, Martinez-Gamboa L, Meier S , et al. Bronchoalveolar lavage fluid cytokines and chemokines as markers and predictors for the outcome of interstitial lung disease in systemic sclerosis patients. Arthritis Res Ther 2009; 11 (4) R111
    CrossrefPubMedGoogle Scholar
  • 70 Hasegawa M, Fujimoto M, Matsushita T, Hamaguchi Y, Takehara K, Sato S. Serum chemokine and cytokine levels as indicators of disease activity in patients with systemic sclerosis. Clin Rheumatol 2011; 30 (2) 231-237
    CrossrefPubMedGoogle Scholar
  • 71 Campioni D, Lo Monaco A, Lanza F , et al. CXCR4 pos circulating progenitor cells coexpressing monocytic and endothelial markers correlating with fibrotic clinical features are present in the peripheral blood of patients affected by systemic sclerosis. Haematologica 2008; 93 (8) 1233-1237
    CrossrefPubMedGoogle Scholar
  • 72 Song JW, Do KH, Jang SJ, Colby TV, Han S, Kim DS. Blood biomarkers MMP-7 and SP-A: predictors of outcome in idiopathic pulmonary fibrosis. Chest 2013; 143 (5) 1422-1429
    CrossrefPubMedGoogle Scholar
  • 73 Moinzadeh P, Krieg T, Hellmich M , et al. Elevated MMP-7 levels in patients with systemic sclerosis: correlation with pulmonary involvement. Exp Dermatol 2011; 20 (9) 770-773
    CrossrefPubMedGoogle Scholar
  • 74 Kim WU, Min SY, Cho ML , et al. Elevated matrix metalloproteinase-9 in patients with systemic sclerosis. Arthritis Res Ther 2005; 7 (1) R71-R79
    CrossrefPubMedGoogle Scholar
  • 75 Andersen GN, Nilsson K, Pourazar J , et al. Bronchoalveolar matrix metalloproteinase 9 relates to restrictive lung function impairment in systemic sclerosis. Respir Med 2007; 101 (10) 2199-2206
    CrossrefPubMedGoogle Scholar
  • 76 Manetti M, Guiducci S, Romano E , et al. Increased serum levels and tissue expression of matrix metalloproteinase-12 in patients with systemic sclerosis: correlation with severity of skin and pulmonary fibrosis and vascular damage. Ann Rheum Dis 2012; 71 (6) 1064-1072
    CrossrefPubMedGoogle Scholar
  • 77 Kikuchi K, Kubo M, Sato S, Fujimoto M, Tamaki K. Serum tissue inhibitor of metalloproteinases in patients with systemic sclerosis. J Am Acad Dermatol 1995; 33 (6) 973-978
    CrossrefPubMedGoogle Scholar
  • 78 Taniguchi T, Asano Y, Akamata K , et al. Serum levels of ADAM12-S: possible association with the initiation and progression of dermal fibrosis and interstitial lung disease in patients with systemic sclerosis. J Eur Acad Dermatol Venereol 2013; 27 (6) 747-753
    CrossrefPubMedGoogle Scholar
  • 79 Oka S, Furukawa H, Shimada K , et al. Serum biomarker analysis of collagen disease patients with acute-onset diffuse interstitial lung disease. BMC Immunol 2013; 14: 9
    CrossrefPubMedGoogle Scholar
  • 80 Tripathi SS, Mishra V, Shukla M , et al. IL-6 receptor-mediated lung Th2 cytokine networking in silica-induced pulmonary fibrosis. Arch Toxicol 2010; 84 (12) 947-955
    CrossrefPubMedGoogle Scholar
  • 81 Chang CH, Hsiao CF, Yeh YM , et al. Circulating interleukin-6 level is a prognostic marker for survival in advanced nonsmall cell lung cancer patients treated with chemotherapy. Int J Cancer 2013; 132 (9) 1977-1985
    CrossrefPubMedGoogle Scholar
  • 82 Simeonova PP, Toriumi W, Kommineni C , et al. Molecular regulation of IL-6 activation by asbestos in lung epithelial cells: role of reactive oxygen species. J Immunol 1997; 159 (8) 3921-3928
    PubMedGoogle Scholar
  • 83 De Lauretis A, Sestini P, Pantelidis P , et al. Serum interleukin 6 is predictive of early functional decline and mortality in interstitial lung disease associated with systemic sclerosis. J Rheumatol 2013; 40 (4) 435-446
    CrossrefPubMedGoogle Scholar
  • 84 Wuttge DM, Wildt M, Geborek P, Wollheim FA, Scheja A, Akesson A. Serum IL-15 in patients with early systemic sclerosis: a potential novel marker of lung disease. Arthritis Res Ther 2007; 9 (5) R85
    CrossrefPubMedGoogle Scholar
  • 85 Kurasawa K, Hirose K, Sano H , et al. Increased interleukin-17 production in patients with systemic sclerosis. Arthritis Rheum 2000; 43 (11) 2455-2463
    CrossrefPubMedGoogle Scholar
  • 86 Komura K, Fujimoto M, Hasegawa M , et al. Increased serum interleukin 23 in patients with systemic sclerosis. J Rheumatol 2008; 35 (1) 120-125
    PubMedGoogle Scholar
  • 87 Truchetet ME, Brembilla NC, Montanari E, Allanore Y, Chizzolini C. Increased frequency of circulating Th22 in addition to Th17 and Th2 lymphocytes in systemic sclerosis: association with interstitial lung disease. Arthritis Res Ther 2011; 13 (5) R166
    CrossrefPubMedGoogle Scholar
  • 88 Martinez-Lostao L, Marzo I, Anel A, Naval J. Targeting the Apo2L/TRAIL system for the therapy of autoimmune diseases and cancer. Biochem Pharmacol 2012; 83 (11) 1475-1483
    CrossrefPubMedGoogle Scholar
  • 89 Azab NA, Rady HM, Marzouk SA. Elevated serum TRAIL levels in scleroderma patients and its possible association with pulmonary involvement. Clin Rheumatol 2012; 31 (9) 1359-1364
    CrossrefPubMedGoogle Scholar
  • 90 Günther A, Korfei M, Mahavadi P, von der Beck D, Ruppert C, Markart P. Unravelling the progressive pathophysiology of idiopathic pulmonary fibrosis. Eur Respir Rev 2012; 21 (124) 152-160
    CrossrefPubMedGoogle Scholar
  • 91 Cambrey AD, Harrison NK, Dawes KE , et al. Increased levels of endothelin-1 in bronchoalveolar lavage fluid from patients with systemic sclerosis contribute to fibroblast mitogenic activity in vitro. Am J Respir Cell Mol Biol 1994; 11 (4) 439-445
    CrossrefPubMedGoogle Scholar
  • 92 Abraham DJ, Vancheeswaran R, Dashwood MR , et al. Increased levels of endothelin-1 and differential endothelin type A and B receptor expression in scleroderma-associated fibrotic lung disease. Am J Pathol 1997; 151 (3) 831-841
    PubMedGoogle Scholar
  • 93 Ihn H, Sato S, Fujimoto M, Takehara K, Tamaki K. Increased serum levels of soluble vascular cell adhesion molecule-1 and E-selectin in patients with systemic sclerosis. Br J Rheumatol 1998; 37 (11) 1188-1192
    CrossrefPubMedGoogle Scholar
  • 94 Kuryliszyn-Moskal A, Klimiuk PA, Sierakowski S. Soluble adhesion molecules (sVCAM-1, sE-selectin), vascular endothelial growth factor (VEGF) and endothelin-1 in patients with systemic sclerosis: relationship to organ systemic involvement. Clin Rheumatol 2005; 24 (2) 111-116
    CrossrefPubMedGoogle Scholar
  • 95 Vancheeswaran R, Magoulas T, Efrat G , et al. Circulating endothelin-1 levels in systemic sclerosis subsets—a marker of fibrosis or vascular dysfunction?. J Rheumatol 1994; 21 (10) 1838-1844
    PubMedGoogle Scholar
  • 96 Costabel U, Guzman J, Bonella F, Oshimo S. Bronchoalveolar lavage in other interstitial lung diseases. Semin Respir Crit Care Med 2007; 28 (5) 514-524
    Article in Thieme ConnectPubMedGoogle Scholar
  • 97 Bouros D, Wells AU, Nicholson AG , et al. Histopathologic subsets of fibrosing alveolitis in patients with systemic sclerosis and their relationship to outcome. Am J Respir Crit Care Med 2002; 165 (12) 1581-1586
    CrossrefPubMedGoogle Scholar
  • 98 Wells AU, Hansell DM, Rubens MB , et al. Fibrosing alveolitis in systemic sclerosis. Bronchoalveolar lavage findings in relation to computed tomographic appearance. Am J Respir Crit Care Med 1994; 150 (2) 462-468
    CrossrefPubMedGoogle Scholar
  • 99 Wells AU, Hansell DM, Haslam PL , et al. Bronchoalveolar lavage cellularity: lone cryptogenic fibrosing alveolitis compared with the fibrosing alveolitis of systemic sclerosis. Am J Respir Crit Care Med 1998; 157 (5, Pt 1) 1474-1482
    CrossrefPubMedGoogle Scholar
  • 100 Behr J, Vogelmeier C, Beinert T , et al. Bronchoalveolar lavage for evaluation and management of scleroderma disease of the lung. Am J Respir Crit Care Med 1996; 154 (2, Pt 1) 400-406
    CrossrefPubMedGoogle Scholar
  • 101 Goh NS, Veeraraghavan S, Desai SR , et al. Bronchoalveolar lavage cellular profiles in patients with systemic sclerosis-associated interstitial lung disease are not predictive of disease progression. Arthritis Rheum 2007; 56 (6) 2005-2012
    CrossrefPubMedGoogle Scholar
  • 102 Tashkin DP, Elashoff R, Clements PJ , et al; Scleroderma Lung Study Research Group. Effects of 1-year treatment with cyclophosphamide on outcomes at 2 years in scleroderma lung disease. Am J Respir Crit Care Med 2007; 176 (10) 1026-1034
    CrossrefPubMedGoogle Scholar
  • 103 Strange C, Bolster MB, Roth MD , et al; Scleroderma Lung Study Research Group. Bronchoalveolar lavage and response to cyclophosphamide in scleroderma interstitial lung disease. Am J Respir Crit Care Med 2008; 177 (1) 91-98
    CrossrefPubMedGoogle Scholar
  • 104 Fischer A, Meehan RT, Feghali-Bostwick CA, West SG, Brown KK. Unique characteristics of systemic sclerosis sine scleroderma-associated interstitial lung disease. Chest 2006; 130 (4) 976-981
    CrossrefPubMedGoogle Scholar
  • 105 Sato LT, Kayser C, Andrade LE. Nailfold capillaroscopy abnormalities correlate with cutaneous and visceral involvement in systemic sclerosis patients. Acta Reumatol Port 2009; 34 (2A): 219-227
    PubMedGoogle Scholar
  • 106 Bredemeier M, Xavier RM, Capobianco KG , et al. Nailfold capillary microscopy can suggest pulmonary disease activity in systemic sclerosis. J Rheumatol 2004; 31 (2) 286-294
    PubMedGoogle Scholar
  • 107 Corrado A, Carpagnano GE, Gaudio A, Foschino-Barbaro MP, Cantatore FP. Nailfold capillaroscopic findings in systemic sclerosis related lung fibrosis and in idiopathic lung fibrosis. Joint Bone Spine 2010; 77 (6) 570-574
    CrossrefPubMedGoogle Scholar
  • 108 Douglas WW, Tazelaar HD, Hartman TE , et al. Polymyositis-dermatomyositis-associated interstitial lung disease. Am J Respir Crit Care Med 2001; 164 (7) 1182-1185
    CrossrefPubMedGoogle Scholar
  • 109 Tazelaar HD, Viggiano RW, Pickersgill J, Colby TV. Interstitial lung disease in polymyositis and dermatomyositis. Clinical features and prognosis as correlated with histologic findings. Am Rev Respir Dis 1990; 141 (3) 727-733
    CrossrefPubMedGoogle Scholar
  • 110 Fathi M, Lundberg IE, Tornling G. Pulmonary complications of polymyositis and dermatomyositis. Semin Respir Crit Care Med 2007; 28 (4) 451-458
    Article in Thieme ConnectPubMedGoogle Scholar
  • 111 Airio A, Kautiainen H, Hakala M. Prognosis and mortality of polymyositis and dermatomyositis patients. Clin Rheumatol 2006; 25 (2) 234-239
    CrossrefPubMedGoogle Scholar
  • 112 Ponyi A, Constantin T, Balogh Z , et al. Disease course, frequency of relapses and survival of 73 patients with juvenile or adult dermatomyositis. Clin Exp Rheumatol 2005; 23 (1) 50-56
    PubMedGoogle Scholar
  • 113 Connors GR, Christopher-Stine L, Oddis CV, Danoff SK. Interstitial lung disease associated with the idiopathic inflammatory myopathies: what progress has been made in the past 35 years?. Chest 2010; 138 (6) 1464-1474
    CrossrefPubMedGoogle Scholar
  • 114 Fathi M, Vikgren J, Boijsen M , et al. Interstitial lung disease in polymyositis and dermatomyositis: longitudinal evaluation by pulmonary function and radiology. Arthritis Rheum 2008; 59 (5) 677-685
    CrossrefPubMedGoogle Scholar
  • 115 Mimori T, Nakashima R, Hosono Y. Interstitial lung disease in myositis: clinical subsets, biomarkers, and treatment. Curr Rheumatol Rep 2012; 14 (3) 264-274
    CrossrefPubMedGoogle Scholar
  • 116 Yokoyama T, Sakamoto T, Shida N , et al. Fatal rapidly progressive interstitial pneumonitis associated with amyopathic dermatomyositis and CD8 T lymphocytes. J Intensive Care Med 2005; 20 (3) 160-163
    CrossrefPubMedGoogle Scholar
  • 117 Suda T, Fujisawa T, Enomoto N , et al. Interstitial lung diseases associated with amyopathic dermatomyositis. Eur Respir J 2006; 28 (5) 1005-1012
    CrossrefPubMedGoogle Scholar
  • 118 Matsushita T, Hasegawa M, Fujimoto M , et al. Clinical evaluation of anti-aminoacyl tRNA synthetase antibodies in Japanese patients with dermatomyositis. J Rheumatol 2007; 34 (5) 1012-1018
    PubMedGoogle Scholar
  • 119 Hamaguchi Y, Fujimoto M, Matsushita T , et al. Common and distinct clinical features in adult patients with anti-aminoacyl-tRNA synthetase antibodies: heterogeneity within the syndrome. PLoS ONE 2013; 8 (4) e60442
    CrossrefPubMedGoogle Scholar
  • 120 Ghirardello A, Bassi N, Palma L , et al. Autoantibodies in polymyositis and dermatomyositis. Curr Rheumatol Rep 2013; 15 (6) 335
    CrossrefPubMedGoogle Scholar
  • 121 Yoshida S, Akizuki M, Mimori T, Yamagata H, Inada S, Homma M. The precipitating antibody to an acidic nuclear protein antigen, the Jo-1, in connective tissue diseases. A marker for a subset of polymyositis with interstitial pulmonary fibrosis. Arthritis Rheum 1983; 26 (5) 604-611
    CrossrefPubMedGoogle Scholar
  • 122 Hirakata M, Suwa A, Nagai S , et al. Anti-KS: identification of autoantibodies to asparaginyl-transfer RNA synthetase associated with interstitial lung disease. J Immunol 1999; 162 (4) 2315-2320
    PubMedGoogle Scholar
  • 123 Sato S, Kuwana M, Hirakata M. Clinical characteristics of Japanese patients with anti-OJ (anti-isoleucyl-tRNA synthetase) autoantibodies. Rheumatology (Oxford) 2007; 46 (5) 842-845
    CrossrefPubMedGoogle Scholar
  • 124 Stone KB, Oddis CV, Fertig N , et al. Anti-Jo-1 antibody levels correlate with disease activity in idiopathic inflammatory myopathy. Arthritis Rheum 2007; 56 (9) 3125-3131
    CrossrefPubMedGoogle Scholar
  • 125 La Corte R, Lo Mo Naco A, Locaputo A, Dolzani F, Trotta F. In patients with antisynthetase syndrome the occurrence of anti-Ro/SSA antibodies causes a more severe interstitial lung disease. Autoimmunity 2006; 39 (3) 249-253
    CrossrefPubMedGoogle Scholar
  • 126 Kunimasa K, Arita M, Nakazawa T , et al. The clinical characteristics of two anti-OJ (anti-isoleucyl-tRNA synthetase) autoantibody-positive interstitial lung disease patients with polymyositis/dermatomyositis. Intern Med 2012; 51 (24) 3405-3410
    CrossrefPubMedGoogle Scholar
  • 127 Sato S, Hirakata M, Kuwana M , et al. Autoantibodies to a 140-kd polypeptide, CADM-140, in Japanese patients with clinically amyopathic dermatomyositis. Arthritis Rheum 2005; 52 (5) 1571-1576
    CrossrefPubMedGoogle Scholar
  • 128 Nakashima R, Imura Y, Kobayashi S , et al. The RIG-I-like receptor IFIH1/MDA5 is a dermatomyositis-specific autoantigen identified by the anti-CADM-140 antibody. Rheumatology (Oxford) 2010; 49 (3) 433-440
    CrossrefPubMedGoogle Scholar
  • 129 Hoshino K, Muro Y, Sugiura K, Tomita Y, Nakashima R, Mimori T. Anti-MDA5 and anti-TIF1-gamma antibodies have clinical significance for patients with dermatomyositis. Rheumatology (Oxford) 2010; 49 (9) 1726-1733
    CrossrefPubMedGoogle Scholar
  • 130 Sato S, Kuwana M, Fujita T, Suzuki Y. Anti-CADM-140/MDA5 autoantibody titer correlates with disease activity and predicts disease outcome in patients with dermatomyositis and rapidly progressive interstitial lung disease. Mod Rheumatol 2013; 23 (3) 496-502
    CrossrefPubMedGoogle Scholar
  • 131 Tanizawa K, Handa T, Nakashima R , et al. HRCT features of interstitial lung disease in dermatomyositis with anti-CADM-140 antibody. Respir Med 2011; 105 (9) 1380-1387
    CrossrefPubMedGoogle Scholar
  • 132 Tanizawa K, Handa T, Nakashima R , et al. The prognostic value of HRCT in myositis-associated interstitial lung disease. Respir Med 2013; 107 (5) 745-752
    CrossrefPubMedGoogle Scholar
  • 133 Bandoh S, Fujita J, Ohtsuki Y , et al. Sequential changes of KL-6 in sera of patients with interstitial pneumonia associated with polymyositis/dermatomyositis. Ann Rheum Dis 2000; 59 (4) 257-262
    CrossrefPubMedGoogle Scholar
  • 134 Kubo M, Ihn H, Yamane K , et al. Serum KL-6 in adult patients with polymyositis and dermatomyositis. Rheumatology (Oxford) 2000; 39 (6) 632-636
    CrossrefPubMedGoogle Scholar
  • 135 Ohnishi H, Yokoyama A, Kondo K , et al. Comparative study of KL-6, surfactant protein-A, surfactant protein-D, and monocyte chemoattractant protein-1 as serum markers for interstitial lung diseases. Am J Respir Crit Care Med 2002; 165 (3) 378-381
    CrossrefPubMedGoogle Scholar
  • 136 Fathi M, Barbasso Helmers S, Lundberg IE. KL-6: a serological biomarker for interstitial lung disease in patients with polymyositis and dermatomyositis. J Intern Med 2012; 271 (6) 589-597
    CrossrefPubMedGoogle Scholar
  • 137 Kumánovics G, Minier T, Radics J, Pálinkás L, Berki T, Czirják L. Comprehensive investigation of novel serum markers of pulmonary fibrosis associated with systemic sclerosis and dermato/polymyositis. Clin Exp Rheumatol 2008; 26 (3) 414-420
    PubMedGoogle Scholar
  • 138 Gono T, Kawaguchi Y, Hara M , et al. Increased ferritin predicts development and severity of acute interstitial lung disease as a complication of dermatomyositis. Rheumatology (Oxford) 2010; 49 (7) 1354-1360
    CrossrefPubMedGoogle Scholar
  • 139 Gono T, Kawaguchi Y, Ozeki E , et al. Serum ferritin correlates with activity of anti-MDA5 antibody-associated acute interstitial lung disease as a complication of dermatomyositis. Mod Rheumatol 2011; 21 (2) 223-227
    CrossrefPubMedGoogle Scholar
  • 140 Gono T, Sato S, Kawaguchi Y , et al. Anti-MDA5 antibody, ferritin and IL-18 are useful for the evaluation of response to treatment in interstitial lung disease with anti-MDA5 antibody-positive dermatomyositis. Rheumatology (Oxford) 2012; 51 (9) 1563-1570
    CrossrefPubMedGoogle Scholar
  • 141 Ihn H, Asano Y, Kubo M , et al. Clinical significance of serum surfactant protein D (SP-D) in patients with polymyositis/dermatomyositis: correlation with interstitial lung disease. Rheumatology (Oxford) 2002; 41 (11) 1268-1272
    CrossrefPubMedGoogle Scholar
  • 142 Satoh H, Kurishima K, Ishikawa H, Ohtsuka M. Increased levels of KL-6 and subsequent mortality in patients with interstitial lung diseases. J Intern Med 2006; 260 (5) 429-434
    CrossrefPubMedGoogle Scholar
  • 143 Arai S, Kurasawa K, Maezawa R, Owada T, Okada H, Fukuda T. Marked increase in serum KL-6 and surfactant protein D levels during the first 4 weeks after treatment predicts poor prognosis in patients with active interstitial pneumonia associated with polymyositis/dermatomyositis. Mod Rheumatol 2013; 23 (5) 872-883
    CrossrefPubMedGoogle Scholar
  • 144 Zandman-Goddard G, Shoenfeld Y. Ferritin in autoimmune diseases. Autoimmun Rev 2007; 6 (7) 457-463
    CrossrefPubMedGoogle Scholar
  • 145 Gono T, Kawaguchi Y, Satoh T , et al. Clinical manifestation and prognostic factor in anti-melanoma differentiation-associated gene 5 antibody-associated interstitial lung disease as a complication of dermatomyositis. Rheumatology (Oxford) 2010; 49 (9) 1713-1719
    CrossrefPubMedGoogle Scholar
  • 146 Tucci M, Quatraro C, Dammacco F, Silvestris F. Increased IL-18 production by dendritic cells in active inflammatory myopathies. Ann N Y Acad Sci 2007; 1107: 184-192
    CrossrefPubMedGoogle Scholar
  • 147 Wang PZ, Guan JL, Han XH. The predictive factors and unfavourable prognostic factors of interstitial lung disease in patients with polymyositis/dermatomyositis [in Chinese]. Zhonghua Jie He He Hu Xi Za Zhi 2008; 31 (6) 417-420
    PubMedGoogle Scholar
  • 148 Krystufková O, Vallerskog T, Helmers SB , et al. Increased serum levels of B cell activating factor (BAFF) in subsets of patients with idiopathic inflammatory myopathies. Ann Rheum Dis 2009; 68 (6) 836-843
    CrossrefPubMedGoogle Scholar
  • 149 Okada M, Suzuki K, Nakanishi T, Nakashima M. Serum levels of KL-6 are positively correlated with those of CA15-3 in patients with interstitial pneumonia associated with collagen diseases. Respirology 2006; 11 (4) 509-510
    CrossrefPubMedGoogle Scholar
  • 150 Antoniou KM, Margaritopoulos G, Economidou F, Siafakas NM. Pivotal clinical dilemmas in collagen vascular diseases associated with interstitial lung involvement. Eur Respir J 2009; 33 (4) 882-896
    CrossrefPubMedGoogle Scholar
  • 151 Marie I, Hachulla E, Chérin P , et al. Interstitial lung disease in polymyositis and dermatomyositis. Arthritis Rheum 2002; 47 (6) 614-622
    CrossrefPubMedGoogle Scholar
  • 152 Schnabel A, Reuter M, Biederer J, Richter C, Gross WL. Interstitial lung disease in polymyositis and dermatomyositis: clinical course and response to treatment. Semin Arthritis Rheum 2003; 32 (5) 273-284
    CrossrefPubMedGoogle Scholar
  • 153 Froidevaux-Janin S, Dudler J, Nicod LP, Lazor R. Interstitial lung disease in rheumatoid arthritis [in French]. Rev Med Suisse 2011; 7 (318) 2272-2277
    PubMedGoogle Scholar
  • 154 Gizinski AM, Mascolo M, Loucks JL , et al. Rheumatoid arthritis (RA)-specific autoantibodies in patients with interstitial lung disease and absence of clinically apparent articular RA. Clin Rheumatol 2009; 28 (5) 611-613
    CrossrefPubMedGoogle Scholar
  • 155 Keith RC, Powers JL, Redente EF , et al. A novel model of rheumatoid arthritis-associated interstitial lung disease in SKG mice. Exp Lung Res 2012; 38 (2) 55-66
    CrossrefPubMedGoogle Scholar
  • 156 Marigliano B, Soriano A, Margiotta D, Vadacca M, Afeltra A. Lung involvement in connective tissue diseases: a comprehensive review and a focus on rheumatoid arthritis. Autoimmun Rev 2013; 12 (11) 1076-1084
    CrossrefPubMedGoogle Scholar
  • 157 Alexiou I, Germenis A, Koutroumpas A, Kontogianni A, Theodoridou K, Sakkas LI. Anti-cyclic citrullinated peptide-2 (CCP2) autoantibodies and extra-articular manifestations in Greek patients with rheumatoid arthritis. Clin Rheumatol 2008; 27 (4) 511-513
    CrossrefPubMedGoogle Scholar
  • 158 Mori S, Koga Y, Sugimoto M. Different risk factors between interstitial lung disease and airway disease in rheumatoid arthritis. Respir Med 2012; 106 (11) 1591-1599
    CrossrefPubMedGoogle Scholar
  • 159 Aubart F, Crestani B, Nicaise-Roland P , et al. High levels of anti-cyclic citrullinated peptide autoantibodies are associated with co-occurrence of pulmonary diseases with rheumatoid arthritis. J Rheumatol 2011; 38 (6) 979-982
    CrossrefPubMedGoogle Scholar
  • 160 Nielen MM, van Schaardenburg D, Reesink HW , et al. Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. Arthritis Rheum 2004; 50 (2) 380-386
    CrossrefPubMedGoogle Scholar
  • 161 Oliver JE, Silman AJ. Risk factors for the development of rheumatoid arthritis. Scand J Rheumatol 2006; 35 (3) 169-174
    CrossrefPubMedGoogle Scholar
  • 162 Masdottir B, Jónsson T, Manfredsdottir V, Víkingsson A, Brekkan A, Valdimarsson H. Smoking, rheumatoid factor isotypes and severity of rheumatoid arthritis. Rheumatology (Oxford) 2000; 39 (11) 1202-1205
    CrossrefPubMedGoogle Scholar
  • 163 Manfredsdottir VF, Vikingsdottir T, Jonsson T , et al. The effects of tobacco smoking and rheumatoid factor seropositivity on disease activity and joint damage in early rheumatoid arthritis. Rheumatology (Oxford) 2006; 45 (6) 734-740
    CrossrefPubMedGoogle Scholar
  • 164 Wolfe F. The effect of smoking on clinical, laboratory, and radiographic status in rheumatoid arthritis. J Rheumatol 2000; 27 (3) 630-637
    PubMedGoogle Scholar
  • 165 Sakaida H. IgG rheumatoid factor in rheumatoid arthritis with interstitial lung disease [in Japanese]. Ryumachi 1995; 35 (4) 671-677
    PubMedGoogle Scholar
  • 166 Wegner N, Lundberg K, Kinloch A , et al. Autoimmunity to specific citrullinated proteins gives the first clues to the etiology of rheumatoid arthritis. Immunol Rev 2010; 233 (1) 34-54
    CrossrefPubMedGoogle Scholar
  • 167 Sokolove J, Bromberg R, Deane KD , et al. Autoantibody epitope spreading in the pre-clinical phase predicts progression to rheumatoid arthritis. PLoS ONE 2012; 7 (5) e35296
    CrossrefPubMedGoogle Scholar
  • 168 van de Stadt LA, van der Horst AR, de Koning MH , et al. The extent of the anti-citrullinated protein antibody repertoire is associated with arthritis development in patients with seropositive arthralgia. Ann Rheum Dis 2011; 70 (1) 128-133
    CrossrefPubMedGoogle Scholar
  • 169 Deane KD, Nicolls MR. Developing better biomarkers for connective tissue disease-associated interstitial lung disease: citrullinated hsp90 autoantibodies in rheumatoid arthritis. Arthritis Rheum 2013; 65 (4) 864-868
    CrossrefPubMedGoogle Scholar
  • 170 Klareskog L, Stolt P, Lundberg K , et al. A new model for an etiology of rheumatoid arthritis: smoking may trigger HLA-DR (shared epitope)-restricted immune reactions to autoantigens modified by citrullination. Arthritis Rheum 2006; 54 (1) 38-46
    CrossrefPubMedGoogle Scholar
  • 171 Fischer A, Solomon JJ, du Bois RM , et al. Lung disease with anti-CCP antibodies but not rheumatoid arthritis or connective tissue disease. Respir Med 2012; 106 (7) 1040-1047
    CrossrefPubMedGoogle Scholar
  • 172 Demoruelle MK, Deane K. Antibodies to citrullinated protein antigens (ACPAs): clinical and pathophysiologic significance. Curr Rheumatol Rep 2011; 13 (5) 421-430
    CrossrefPubMedGoogle Scholar
  • 173 Harlow L, Rosas IO, Gochuico BR , et al. Identification of citrullinated hsp90 isoforms as novel autoantigens in rheumatoid arthritis-associated interstitial lung disease. Arthritis Rheum 2013; 65 (4) 869-879
    CrossrefPubMedGoogle Scholar
  • 174 Kahloon RA, Xue J, Bhargava A , et al. Patients with idiopathic pulmonary fibrosis with antibodies to heat shock protein 70 have poor prognoses. Am J Respir Crit Care Med 2013; 187 (7) 768-775
    CrossrefPubMedGoogle Scholar
  • 175 Hassan WU, Keaney NP, Holland CD, Kelly CA. Association of HLA-DR4, protease inhibitor phenotypes and keratoconjunctivitis sicca with pulmonary abnormalities in rheumatoid arthritis. Br J Rheumatol 1995; 34 (1) 37-40
    CrossrefPubMedGoogle Scholar
  • 176 Hillarby MC, McMahon MJ, Grennan DM , et al. HLA associations in subjects with rheumatoid arthritis and bronchiectasis but not with other pulmonary complications of rheumatoid disease. Br J Rheumatol 1993; 32 (9) 794-797
    CrossrefPubMedGoogle Scholar
  • 177 Furukawa H, Oka S, Shimada K , et al. Association of human leukocyte antigen with interstitial lung disease in rheumatoid arthritis: a protective role for shared epitope. PLoS ONE 2012; 7 (5) e33133
    CrossrefPubMedGoogle Scholar
  • 178 Migita K, Nakamura T, Koga T, Eguchi K. HLA-DRB1 alleles and rheumatoid arthritis-related pulmonary fibrosis. J Rheumatol 2010; 37 (1) 205-207
    CrossrefPubMedGoogle Scholar
  • 179 Kinoshita F, Hamano H, Harada H , et al. Role of KL-6 in evaluating the disease severity of rheumatoid lung disease: comparison with HRCT. Respir Med 2004; 98 (11) 1131-1137
    CrossrefPubMedGoogle Scholar
  • 180 Oyama T, Kohno N, Yokoyama A , et al. Detection of interstitial pneumonitis in patients with rheumatoid arthritis by measuring circulating levels of KL-6, a human MUC1 mucin. Lung 1997; 175 (6) 379-385
    CrossrefPubMedGoogle Scholar
  • 181 Nakajima H, Harigai M, Hara M , et al. KL-6 as a novel serum marker for interstitial pneumonia associated with collagen diseases. J Rheumatol 2000; 27 (5) 1164-1170
    PubMedGoogle Scholar
  • 182 Kobayashi J, Kitamura S. KL-6: a serum marker for interstitial pneumonia. Chest 1995; 108 (2) 311-315
    CrossrefPubMedGoogle Scholar
  • 183 Kohno N, Kyoizumi S, Awaya Y, Fukuhara H, Yamakido M, Akiyama M. New serum indicator of interstitial pneumonitis activity. Sialylated carbohydrate antigen KL-6. Chest 1989; 96 (1) 68-73
    CrossrefPubMedGoogle Scholar
  • 184 Takamura A, Hirata S, Nagasawa H , et al. A retrospective study of serum KL-6 levels during treatment with biological disease-modifying antirheumatic drugs in rheumatoid arthritis patients: a report from the Ad Hoc Committee for Safety of Biological DMARDs of the Japan College of Rheumatology. Mod Rheumatol 2013; 23 (2) 297-303
    CrossrefPubMedGoogle Scholar
  • 185 Harigai M, Takamura A, Atsumi T , et al. Elevation of KL-6 serum levels in clinical trials of tumor necrosis factor inhibitors in patients with rheumatoid arthritis: a report from the Japan College of Rheumatology Ad Hoc Committee for Safety of Biological DMARDs. Mod Rheumatol 2013; 23 (2) 284-296
    CrossrefPubMedGoogle Scholar
  • 186 Gabbay E, Tarala R, Will R , et al. Interstitial lung disease in recent onset rheumatoid arthritis. Am J Respir Crit Care Med 1997; 156 (2, Pt 1): 528-535
    CrossrefPubMedGoogle Scholar
  • 187 Gilligan DM, O'Connor CM, Ward K, Moloney D, Bresnihan B, FitzGerald MX. Bronchoalveolar lavage in patients with mild and severe rheumatoid lung disease. Thorax 1990; 45 (8) 591-596
    CrossrefPubMedGoogle Scholar
  • 188 Garcia JG, Parhami N, Killam D, Garcia PL, Keogh BA. Bronchoalveolar lavage fluid evaluation in rheumatoid arthritis. Am Rev Respir Dis 1986; 133 (3) 450-454
    PubMedGoogle Scholar
  • 189 Ascherman DP. Interstitial lung disease in rheumatoid arthritis. Curr Rheumatol Rep 2010; 12 (5) 363-369
    CrossrefPubMedGoogle Scholar
  • 190 Gochuico BR, Avila NA, Chow CK , et al. Progressive preclinical interstitial lung disease in rheumatoid arthritis. Arch Intern Med 2008; 168 (2) 159-166
    CrossrefPubMedGoogle Scholar
  • 191 Park JH, Kim DS, Park IN , et al. Prognosis of fibrotic interstitial pneumonia: idiopathic versus collagen vascular disease-related subtypes. Am J Respir Crit Care Med 2007; 175 (7) 705-711
    CrossrefPubMedGoogle Scholar
  • 192 Boulware DW, Hedgpeth MT. Lupus pneumonitis and anti-SSA(Ro) antibodies. J Rheumatol 1989; 16 (4) 479-481
    PubMedGoogle Scholar
  • 193 Groen H, ter Borg EJ, Postma DS, Wouda AA, van der Mark TW, Kallenberg CG. Pulmonary function in systemic lupus erythematosus is related to distinct clinical, serologic, and nailfold capillary patterns. Am J Med 1992; 93 (6) 619-627
    CrossrefPubMedGoogle Scholar
  • 194 Nielepkowicz-Goździńska A, Fendler W, Robak E , et al. Exhaled cytokines in systemic lupus erythematosus with lung involvement. Pol Arch Med Wewn 2013; 123 (4) 141-148
    PubMedGoogle Scholar
  • 195 Szekanecz E, Szucs G, Szekanecz Z , et al. Tumor-associated antigens in systemic sclerosis and systemic lupus erythematosus: associations with organ manifestations, immunolaboratory markers and disease activity indices. J Autoimmun 2008; 31 (4) 372-376
    CrossrefPubMedGoogle Scholar
  • 196 Yücel AE, Calguneri M, Ruacan S. False positive pleural biopsy and high CA125 levels in serum and pleural effusion in systemic lupus erythematosus. Clin Rheumatol 1996; 15 (3) 295-297
    CrossrefPubMedGoogle Scholar
  • 197 Takeda N, Ihn H, Teramoto S. Markedly increased levels of IL-6 and CA125 in pleural fluid of an elderly person with overlap syndrome of systemic sclerosis and systemic lupus erythematosus. Age Ageing 2001; 30 (2) 171
    CrossrefPubMedGoogle Scholar
  • 198 Yang Z, Liang Y, Li C, Zhong R. Serum CA125 elevation is independently associated with serositis in SLE patients. Clin Exp Rheumatol 2012; 30 (1) 93-98
    PubMedGoogle Scholar
  • 199 Yazisiz V, Arslan G, Ozbudak IH , et al. Lung involvement in patients with primary Sjögren's syndrome: what are the predictors?. Rheumatol Int 2010; 30 (10) 1317-1324
    CrossrefPubMedGoogle Scholar
  • 200 Yazisiz V, Avci AB, Erbasan F, Kiriş E, Terzioğlu E. Diagnostic performance of minor salivary gland biopsy, serological and clinical data in Sjögren's syndrome: a retrospective analysis. Rheumatol Int 2009; 29 (4) 403-409
    CrossrefPubMedGoogle Scholar
  • 201 Deheinzelin D, Capelozzi VL, Kairalla RA, Barbas Filho JV, Saldiva PH, de Carvalho CR. Interstitial lung disease in primary Sjögren's syndrome. Clinical-pathological evaluation and response to treatment. Am J Respir Crit Care Med 1996; 154 (3, Pt 1) 794-799
    CrossrefPubMedGoogle Scholar
  • 202 Ito I, Nagai S, Kitaichi M , et al. Pulmonary manifestations of primary Sjogren's syndrome: a clinical, radiologic, and pathologic study. Am J Respir Crit Care Med 2005; 171 (6) 632-638
    CrossrefPubMedGoogle Scholar
  • 203 Parambil JG, Myers JL, Lindell RM, Matteson EL, Ryu JH. Interstitial lung disease in primary Sjögren syndrome. Chest 2006; 130 (5) 1489-1495
    CrossrefPubMedGoogle Scholar
  • 204 Sarkar PK, Patel N, Furie RA, Talwar A. Pulmonary manifestations of primary Sjögren's syndrome. Indian J Chest Dis Allied Sci 2009; 51 (2) 93-101
    PubMedGoogle Scholar
  • 205 Davidson BK, Kelly CA, Griffiths ID. Ten year follow up of pulmonary function in patients with primary Sjögren's syndrome. Ann Rheum Dis 2000; 59 (9) 709-712
    CrossrefPubMedGoogle Scholar
  • 206 Takada K, Takiguchi M, Konno A, Inaba M. Autoimmunity against a tissue kallikrein in IQI/Jic Mice: a model for Sjogren's syndrome. J Biol Chem 2005; 280 (5) 3982-3988
    CrossrefPubMedGoogle Scholar
  • 207 Goëb V, Salle V, Duhaut P , et al. Clinical significance of autoantibodies recognizing Sjögren's syndrome A (SSA), SSB, calpastatin and alpha-fodrin in primary Sjögren's syndrome. Clin Exp Immunol 2007; 148 (2) 281-287
    CrossrefPubMedGoogle Scholar
  • 208 Kovács L, Fehér E, Bodnár I , et al. Demonstration of autoantibody binding to muscarinic acetylcholine receptors in the salivary gland in primary Sjögren's syndrome. Clin Immunol 2008; 128 (2) 269-276
    CrossrefPubMedGoogle Scholar
  • 209 Shen L, Suresh L, Lindemann M , et al. Novel autoantibodies in Sjogren's syndrome. Clin Immunol 2012; 145 (3) 251-255
    CrossrefPubMedGoogle Scholar
  • 210 Pertovaara M, Bootorabi F, Kuuslahti M , et al. Carbonic anhydrase autoantibodies and sicca symptoms in primary Sjögreńs syndrome. Clin Exp Rheumatol 2012; 30 (3) 456-457
    PubMedGoogle Scholar
  • 211 Delaleu N, Immervoll H, Cornelius J, Jonsson R. Biomarker profiles in serum and saliva of experimental Sjögren's syndrome: associations with specific autoimmune manifestations. Arthritis Res Ther 2008; 10 (1) R22
    CrossrefPubMedGoogle Scholar
  • 212 Wallaert B, Hatron PY, Grosbois JM, Tonnel AB, Devulder B, Voisin C. Subclinical pulmonary involvement in collagen-vascular diseases assessed by bronchoalveolar lavage. Relationship between alveolitis and subsequent changes in lung function. Am Rev Respir Dis 1986; 133 (4) 574-580
    PubMedGoogle Scholar
  • 213 Hatron PY, Wallaert B, Gosset D , et al. Subclinical lung inflammation in primary Sjögren's syndrome. Relationship between bronchoalveolar lavage cellular analysis findings and characteristics of the disease. Arthritis Rheum 1987; 30 (11) 1226-1231
    CrossrefPubMedGoogle Scholar
  • 214 Wallaert B, Prin L, Hatron PY, Ramon P, Tonnel AB, Voisin C. Lymphocyte subpopulations in bronchoalveolar lavage in Sjögren's syndrome. Evidence for an expansion of cytotoxic/suppressor subset in patients with alveolar neutrophilia. Chest 1987; 92 (6) 1025-1031
    CrossrefPubMedGoogle Scholar
  • 215 Hajas A, Barath S, Szodoray P , et al. Derailed B cell homeostasis in patients with mixed connective tissue disease. Hum Immunol 2013; 74 (7) 833-841
    CrossrefPubMedGoogle Scholar
  • 216 Prakash UB. Lungs in mixed connective tissue disease. J Thorac Imaging 1992; 7 (2) 55-61
    CrossrefPubMedGoogle Scholar
  • 217 Bodolay E, Szekanecz Z, Dévényi K , et al. Evaluation of interstitial lung disease in mixed connective tissue disease (MCTD). Rheumatology (Oxford) 2005; 44 (5) 656-661
    CrossrefPubMedGoogle Scholar
  • 218 Szodoray P, Hajas A, Kardos L , et al. Distinct phenotypes in mixed connective tissue disease: subgroups and survival. Lupus 2012; 21 (13) 1412-1422
    CrossrefPubMedGoogle Scholar
  • 219 Hajas A, Szodoray P, Nakken B , et al. Clinical course, prognosis, and causes of death in mixed connective tissue disease. J Rheumatol 2013; 40 (7) 1134-1142
    CrossrefPubMedGoogle Scholar
  • 220 Ferreira JP, Almeida I, Marinho A, Cerveira C, Vasconcelos C. Anti-ro52 antibodies and interstitial lung disease in connective tissue diseases excluding scleroderma. ISRN Rheumatol 2012; 2012: 415272
    PubMedGoogle Scholar
  • 221 Ferreira R, Barreto M, Santos E , et al. Heritable factors shape natural human IgM reactivity to Ro60/SS-A and may predispose for SLE-associated IgG anti-Ro and anti-La autoantibody production. J Autoimmun 2005; 25 (2) 155-163
    CrossrefPubMedGoogle Scholar
  • 222 Satoh M, Hirayoshi K, Yokota S, Hosokawa N, Nagata K. Intracellular interaction of collagen-specific stress protein HSP47 with newly synthesized procollagen. J Cell Biol 1996; 133 (2) 469-483
    CrossrefPubMedGoogle Scholar
  • 223 Yokota S, Kubota H, Matsuoka Y , et al. Prevalence of HSP47 antigen and autoantibodies to HSP47 in the sera of patients with mixed connective tissue disease. Biochem Biophys Res Commun 2003; 303 (2) 413-418
    CrossrefPubMedGoogle Scholar
  • 224 Kakugawa T, Yokota S, Mukae H , et al. High serum concentrations of autoantibodies to HSP47 in nonspecific interstitial pneumonia compared with idiopathic pulmonary fibrosis. BMC Pulm Med 2008; 8: 23
    CrossrefPubMedGoogle Scholar
  • 225 Mosca M, Tani C, Bombardieri S. Undifferentiated connective tissue diseases (UCTD): a new frontier for rheumatology. Best Pract Res Clin Rheumatol 2007; 21 (6) 1011-1023
    CrossrefPubMedGoogle Scholar
  • 226 Lunardi F, Balestro E, Nordio B , et al. Undifferentiated connective tissue disease presenting with prevalent interstitial lung disease: case report and review of literature. Diagn Pathol 2011; 6: 50
    CrossrefPubMedGoogle Scholar
  • 227 Mosca M, Neri R, Bombardieri S. Undifferentiated connective tissue diseases (UCTD): a review of the literature and a proposal for preliminary classification criteria. Clin Exp Rheumatol 1999; 17 (5) 615-620
    PubMedGoogle Scholar
  • 228 Mosca M, Tani C, Neri C, Baldini C, Bombardieri S. Undifferentiated connective tissue diseases (UCTD). Autoimmun Rev 2006; 6 (1) 1-4
    CrossrefPubMedGoogle Scholar
  • 229 Kinder BW, Collard HR, Koth L , et al. Idiopathic nonspecific interstitial pneumonia: lung manifestation of undifferentiated connective tissue disease?. Am J Respir Crit Care Med 2007; 176 (7) 691-697
    CrossrefPubMedGoogle Scholar
  • 230 Suda T, Kono M, Nakamura Y , et al. Distinct prognosis of idiopathic nonspecific interstitial pneumonia (NSIP) fulfilling criteria for undifferentiated connective tissue disease (UCTD). Respir Med 2010; 104 (10) 1527-1534
    CrossrefPubMedGoogle Scholar
  • 231 Romagnoli M, Gurioli C, Casoni G, Poletti V. Surgical lung biopsy in the diagnosis of idiopathic NSIP: do we always need it in the initial approach?. Am J Respir Crit Care Med 2009; 179 (11) 1071 , author reply 1071–1072
    CrossrefPubMedGoogle Scholar
  • 232 Sato S, Nagaoka T, Hasegawa M, Nishijima C, Takehara K. Elevated serum KL-6 levels in patients with systemic sclerosis: association with the severity of pulmonary fibrosis. Dermatology 2000; 200 (3) 196-201
    CrossrefPubMedGoogle Scholar
  • 233 Antonelli A, Fallahi P, Ferrari SM , et al. Systemic sclerosis fibroblasts show specific alterations of interferon-γ and tumor necrosis factor-α-induced modulation of interleukin 6 and chemokine ligand 2. J Rheumatol 2012; 39 (5) 979-985
    CrossrefPubMedGoogle Scholar
  • 234 Buttmann M, Merzyn C, Hofstetter HH, Rieckmann P. TRAIL, CXCL10 and CCL2 plasma levels during long-term Interferon-beta treatment of patients with multiple sclerosis correlate with flu-like adverse effects but do not predict therapeutic response. J Neuroimmunol 2007; 190 (1–2) 170-176
    CrossrefPubMedGoogle Scholar
  • 235 Gourh P, Arnett FC, Assassi S , et al. Plasma cytokine profiles in systemic sclerosis: associations with autoantibody subsets and clinical manifestations. Arthritis Res Ther 2009; 11 (5) R147
    CrossrefPubMedGoogle Scholar
  • 236 Sato S, Nagaoka T, Hasegawa M , et al. Serum levels of connective tissue growth factor are elevated in patients with systemic sclerosis: association with extent of skin sclerosis and severity of pulmonary fibrosis. J Rheumatol 2000; 27 (1) 149-154
    PubMedGoogle Scholar
  • 237 Muangchan C, Harding S, Khimdas S, Bonner A, Baron M, Pope J ; Canadian Scleroderma Research group. Association of C-reactive protein with high disease activity in systemic sclerosis: results from the Canadian Scleroderma Research Group. Arthritis Care Res (Hoboken) 2012; 64 (9) 1405-1414
    CrossrefPubMedGoogle Scholar
  • 238 Iwata Y, Yoshizaki A, Ogawa F , et al. Increased serum pentraxin 3 in patients with systemic sclerosis. J Rheumatol 2009; 36 (5) 976-983
    CrossrefPubMedGoogle Scholar