RT Journal Article
SR Electronic
T1 Monogenic gene variants in lung transplant recipients with usual interstitial pneumonia
JF ERJ Open Research
JO erjor
FD European Respiratory Society
SP 00583-2021
DO 10.1183/23120541.00583-2021
A1 Christoffer Stark
A1 Juha W. Koskenvuo
A1 Antti Nykänen
A1 Eija H. Seppälä
A1 Samuel Myllykangas
A1 Karl Lemström
A1 Peter Raivio
YR 2021
UL http://openres.ersjournals.com/content/early/2021/12/16/23120541.00583-2021.abstract
AB Question addressed by the study The prevalence of monogenic disease-causing gene variants in lung-transplant recipients with idiopathic pulmonary fibrosis is not fully known. Their impact on clinical outcomes before and after transplantation requires more evidence.Patients and Methods We retrospectively performed sequence analysis of genes associated with pulmonary fibrosis in a cohort of 23 patients with histologically confirmed usual interstitial pneumonia that had previously undergone double lung transplantation. We evaluated the impact of confirmed molecular diagnoses on disease progression, clinical outcomes and incidence of acute rejection or chronic lung allograft dysfunction after transplantation.Results Fifteen patients out of 23 (65%) had a variant in a gene associated with interstitial lung disease. Eleven patients (48%) received a molecular diagnosis, of which nine involved genes for telomerase function. Five diagnostic variants were found in the gene for Telomerase reverse transcriptase. Two of these variants, p.(Asp684Gly) and p.(Arg774*), seemed to be enriched in Finnish lung-transplant recipients. Disease progression and the incidence of acute rejection and chronic lung allograft dysfunction was similar between patients with telomere-related disease and the rest of the study population. The incidence of renal or bone marrow insufficiency or skin malignancies did not differ between the groups.Answer to the question Genetic variants are common in lung transplant recipients with pulmonary fibrosis and are most often related to telomerase function. A molecular diagnosis for telomeropathy does not seem to impact disease progression or the risk of complications or allograft dysfunction after transplantation.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.Conflicts of Interest: Dr. Stark has nothing to disclose.Conflicts of Interest: Dr. Koskenvuo reports personal fees from null, outside the submitted work; .Conflicts of Interest: Dr. Nykänen has nothing to disclose.Conflicts of Interest: Dr. Seppälä reports personal fees from Blueprint Genetics, outside the submitted work; .Conflicts of Interest: Dr. Myllykangas reports personal fees from null, outside the submitted work; .Conflicts of Interest: Dr. LEMSTROM has nothing to disclose.Conflicts of Interest: Dr. Raivio has nothing to disclose.