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Long-Term Follow-Up and Outcome of a Large Cohort of Patients with Common Variable Immunodeficiency

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Common Variable Immunodeficiency belongs to the group of rare diseases encompassing antibody deficiency syndromes of highly variable clinical presentation and outcome. The multicenter prospective study on a cohort of 224 patients with Common Variable Immunodeficiency provides an updated view of the spectrum of illnesses which occurred at the clinical onset and over a long period of follow-up (mean time: 11 years) and information on the effects of long-term immunoglobulin treatment. The mean age at the time of diagnosis was 26.6 years. Seventy-five patients were younger than 14 years of age. The mean age at the onset of symptoms was 16.9 years. This implicates with a mean diagnostic delay of 8.9 years. Respiratory tract infections were the most prominent clinical problem observed at diagnosis and during the follow-up. Intravenous immunoglobulin administration induced a significant reduction in the incidence of acute infections, mainly acute pneumonia and acute otitis. However, a progressive increase in the prevalence of patients with chronic diseases, mainly sinusitis and lung disease, was observed in all age groups, including the pediatric population. The morbidity of Common Variable Immunodeficiency due to all associated clinical conditions increased over time despite an adequate replacement with intravenous immunoglobulins. Our data stressed the need to develop international guidelines for the prevention and therapy of chronic lung disease, chronic sinusitis, chronic diarrhoea, and chronic granulomatosis in patients with humoral immunodeficiencies.

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Abbreviations

CVID:

Common Variable Immunodeficiency

IVIG:

intravenous immunoglobulins

CLD:

chronic lung disease

XLA:

X-linked Agammaglobulinemia

NHL:

non-Hodgkin lymphoma.

REFERENCES

  1. International Union of Immunological Societies: Primary immunodeficiency diseases, report of an IUIS scientific committee. Clin Exp Immunol 118(Suppl 1):1–28, 1999

    Google Scholar 

  2. Conley ME, Notarangelo LD, Etzioni A: Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies). Clin Immunol 93:190–197, 1999

    Article  PubMed  CAS  Google Scholar 

  3. Notarangelo LD, Casanova JL, Fischer A, Puck J, Rosen F, Seger R, Geha R: Primary immunodeficiency diseases: An update. J Allergy Clin Immunol 114:677–687, 2004

    Article  PubMed  CAS  Google Scholar 

  4. Hammarstrom L, Vorechovsky I, Webster D: Selective IgA deficiency and Common Variable Immunodeficiency. Clin Exp Immunol 120:225–231, 2000

    Article  PubMed  CAS  Google Scholar 

  5. Hausser C, Virelizier JL, Buriot D, Griscelli C: Common variable hypogammaglobulinemia in children. Clinical and immunologic observations in 30 patients. Am J Dis Child 137:833–837, 1983

    PubMed  CAS  Google Scholar 

  6. Conley ME, Park CL, Douglas SD: Childhood common variable immunodeficiency with autoimmune disease. J Pediatr 108:915–922, 1986

    Article  PubMed  CAS  Google Scholar 

  7. Hermaszewski RA, WebsterAD: Primary hypogammaglobulinaemia: A survey of clinical manifestations and complications. Q J Med 86:31–42, 1993

    PubMed  CAS  Google Scholar 

  8. Cunningham-Rundles C, Bodian C: Common variable immunodeficiency: Clinical and immunological features of 248 patients. Clin Immunol 92:34–48, 1999

    Article  PubMed  CAS  Google Scholar 

  9. Buehring I, Friedrich B, Schaaf J, Schmidt H, Ahrens P, Zielen S: Chronic sinusitis refractory to standard management in patients with humoral immunodeficiencies. Clin Exp Immunol 109:468–473, 1997

    Article  PubMed  CAS  Google Scholar 

  10. Kainulainen L, Varpula M, Liippo K, Svedstrom E, Nikoskelainen J, Ruuskanen O: Pulmonary abnormalities in patients with primary hypogammaglobulinemia. J Allergy Clin Immunol 104:1031–1036, 1999

    Article  PubMed  CAS  Google Scholar 

  11. Kalha I, Sellin JH: Common variable immunodeficiency and the gastrointestinal tract. Curr Gastroenterol Rep 6:377–383, 2004

    PubMed  Google Scholar 

  12. Skull S, Kemp A: Treatment of hypogammaglobulinemia with intravenous immunoglobulins, 1973–1993. Arch Dis Child 74:527–530, 1996

    Article  PubMed  CAS  Google Scholar 

  13. Stiehm ER: Conventional therapy of primary immunodeficiency diseases. In Primary Immunodeficiency Diseases: A Molecular and Genetic Approach, HD Ochs, CIE Smith, JM Puck (eds). Oxford, Oxford University Press, 1999, pp 448–458

    Google Scholar 

  14. Quinti I, Pierdominici M, Marziali M, Giovannetti A, Donnanno S, Chapel H, et al.: European surveillance of immunoglobulin safety—results of initial survey of 1243 patients with primary immunodeficiencies in 16 countries. Clin Immunol 104:231–236, 2002

    Article  PubMed  CAS  Google Scholar 

  15. Busse PJ, Razvi S, Cunningham-Rundles C: Efficacy of intravenous immunoglobulin in the prevention of pneumonia in patients with common variable immunodeficiency. J Allergy Clin Immunol 109:1001–1004, 2002

    Article  PubMed  CAS  Google Scholar 

  16. Wang J, Cunningham-Rundles C: Treatment and outcome of autoimmune hematologic disease in common variable immunodeficiency (CVID). J Autoimmun 25:57–62, 2005

    Article  PubMed  CAS  Google Scholar 

  17. Roifman CM, Gelfand EW: Replacement therapy with high dose intravenous gammaglobulins improves chronic pulmonary disease in patients with hypogammaglobulinemia. Pediatr Infect Dis J 7:S92–S96, 1988

    Article  PubMed  CAS  Google Scholar 

  18. Quartier P, Debrè M, De Blic J, de Sauverzac R, Sayegh N, Jabado N, et al.: Early and prolonged intravenous immunoglobulin therapy in childhood agammaglobulinemia: A retrospective survey of 31 patients. J Pediatr 134:589–596, 1999

    Article  PubMed  CAS  Google Scholar 

  19. Plebani A, Soresina A, Rondelli R, Amato GM, Azzari C, Cardinale F, et al.: Clinical, immunological, and molecular analysis in a large cohort of patients with X-linked agammaglobulinemia: An Italian multicenter study. Clin Immunol 104:221–230, 2002

    Article  PubMed  CAS  Google Scholar 

  20. Thickett KM, Kumararatne DS, Banerjee AK, Dudley R, Stableforth DE: Common variable immune deficiency: Respiratory manifestations, pulmonary function and high-resolution CT scan findings. Q J Med 95:655–662, 2002

    CAS  Google Scholar 

  21. Carsetti R, Rosado MM, Donnanno S, et al.: The loss of IgM memory B cells correlates with clinical disease in common variable immunodeficiency. J Allergy Clin Immunol 115:412–417, 2005

    Article  PubMed  CAS  Google Scholar 

  22. Lanzavecchia A, Bernasconi N, Traggiai E, Ruprecht CR, Corti D, Sallusto F: Understanding and making use of human memory B cells. Immunol Rev 211:303–309, 2006

    Article  PubMed  CAS  Google Scholar 

  23. Kruetzmann S, Rosado MM, Weber H, et al.: Human immunoglobulin M memory B cells controlling Streptococcus pneumoniae infections are generated in the spleen. J Exp Med 197:939–945, 2003

    Article  PubMed  CAS  Google Scholar 

  24. Amsden GW: Anti-inflammatory effects of macrolides—an underappreciated benefit in the treatment of community-acquired respiratory tract infections and chronic inflammatory pulmonary conditions? J Antimicrob Chemother 55:10–21, 2005

    Article  PubMed  CAS  Google Scholar 

  25. Warnatz K, Denz A, Drager R, et al.: Severe deficiency of switched memory B-cells (CD27+IgM−IgD−) in subgroups of patients with common variable immunodeficiency (CVID): A new approach to classify a heterogeneous disease. Blood 99:1544–1551, 2002

    Article  PubMed  CAS  Google Scholar 

  26. Warnatz K, Wehr C, Drager R, Schmidt S, Eibel H, Schlesier M, et al.: Expansion of CD19(hi)CD21(lo/neg) B cells in common variable immunodeficiency (CVID) patients with autoimmune cytopenia. Immunobiology 206:502–513, 2002

    Article  PubMed  Google Scholar 

  27. Ko J, Radigan L, Cunningham-Rundles C: Immune competence and switched memory B cells in common variable immunodeficiency. Clin Immunol 116:37–41, 2005

    Article  PubMed  CAS  Google Scholar 

  28. Alachkar H, Taubenheim N, Haeney MR, Durandy A, Arkwright PD: Memory switched B cell percentage and not serum immunoglobulin concentration is associated with clinical complications in children and adults with specific antibody deficiency and common variable immunodeficiency. Clin Immunol 120:310–318, 2006

    Article  PubMed  CAS  Google Scholar 

  29. Mechanic LJ, Dikman S, Cunningham-Rundles C: Granulomatous disease in common variable immunodeficiency. Ann Intern Med 127:613–617, 1997

    PubMed  CAS  Google Scholar 

  30. Bates CA, Ellison MC, Lynch DA, Cool CD, Brown KK, Routes JM: Granulomatous-lymphocytic lung disease shortens survival in common variable immunodeficiency. J Allergy Clin Immunol 114:415–421, 2004

    Article  PubMed  Google Scholar 

  31. Mechanic LJ, Dikman S, Cunningham-Rundles C: Granulomatous disease in common variable immunodeficiency. Ann Intern Med 127:613–617, 1997

    PubMed  CAS  Google Scholar 

  32. Kersey JH, Spector BD, Good RA. Primary immunodeficiency diseases and cancer: The immunodeficiency-cancer registry. Int J Cancer 15(12):333–347, 1973

    Article  Google Scholar 

  33. Gompels MM, Hodges E, Lock RJ, Angus B, White H, Larkin A, et al.: Lymphoproliferative disease in antibody deficiency: A multi-centre study. Clin Exp Immunol 134:314–321, 2003

    Article  PubMed  CAS  Google Scholar 

  34. Mellemkjær L, Hammarström L, Andersen V, et al.: Cancer risk among patients with IgA deficiency or common variable immunodeficiency and their relatives: A combined Danish and Swedish study. Clin Exp Immunol 130:495–500, 2002

    Article  PubMed  Google Scholar 

  35. Ko J, Radigan L, Cunningham-Rundles C: Immune competence and switched memory B cells in common variable immunodeficiency. Clin Immunol 116:37–41, 2005

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We would like to thank the Italian Primary Immunodeficiency Patient's Association (AIP) for their help and Dr. Bodo Grimbacker for critical review of the manuscript.

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Authors and Affiliations

  1. Department of Clinical Immunology, University of Rome “La Sapienza” Rome, Viale dell’Università 37 00186, Rome, Italy

    ISABELLA QUINTI, SIMONA DONNANNO, ANNA MARIA PESCE, FEDERICA BORGHESE & ANDREA GUERRA

  2. Department of Paediatrics, University of Brescia, Owensboro, Kentucky, Italy

    ANNAROSA SORESINA & ALESSANDRO PLEBANI

  3. Department of Allergy and Clinical Immunology, University of Naples “Federico II,” Naples, Naples, Italy

    GIUSEPPE SPADARO

  4. Department of Paediatrics, University of Turin, Torino, Italy

    SILVANA MARTINO

  5. Department of Internal Medicine, University of Padua, Padua, Italy

    CARLO AGOSTINI

  6. Department of Pediatrics, University of Naples “Federico II, ” Naples, Italy

    PIGNATA CLAUDIO

  7. Department of Biomedical Sciences, University of Bari, Bari, Italy

    DAMMACCO FRANCO

  8. Department of Onco-Haematology, University of Bologna, Bologna, Italy

    ROBERTO RONDELLI

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  1. ISABELLA QUINTI
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  2. ANNAROSA SORESINA
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  12. ROBERTO RONDELLI
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  13. ALESSANDRO PLEBANI
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Correspondence to ISABELLA QUINTI.

Additional information

WITHIN THE IPINET (Italian Primary Immunodeficiency Network) IPINET: De Mattia D, Martire B, Bari, Cossu F, Cagliari, Schirilló G, Catania, Castagnola E, Genova, Pietrogrande MC, Delle Piane RM, Milano, Putti C, Padova, Trizzino A, Amato GM, Palermo, Bertolini P, Parma, Zecca M, Pavia, Consolini R, Pisa, Moschese V, Rossi P, Cancrini C, Roma, Cazzola GA, Verona

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QUINTI, I., SORESINA, A., SPADARO, G. et al. Long-Term Follow-Up and Outcome of a Large Cohort of Patients with Common Variable Immunodeficiency. J Clin Immunol 27, 308–316 (2007). https://doi.org/10.1007/s10875-007-9075-1

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  • DOI: https://doi.org/10.1007/s10875-007-9075-1

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