Methotrexate treatment efficacy in sarcoidosis might be related to TNF-α polymorphism: real life preliminary study.

Autor:	Goljan Geremek A; 2nd Department of Respiratory Medicine, National Tuberculosis and Lung Diseases Research Institute, Warsaw Poland., Puscinska E; 2nd Department of Respiratory Medicine, National Tuberculosis and Lung Diseases Research Institute, Warsaw Poland., Czystowska M; 2nd Department of Respiratory Medicine, National Tuberculosis and Lung Diseases Research Institute, Warsaw Poland., Skoczylas A; Geriatrics Clinic, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland., Bednarek M; 2nd Department of Respiratory Medicine, National Tuberculosis and Lung Diseases Research Institute, Warsaw Poland., Nowinski A; 2nd Department of Respiratory Medicine, National Tuberculosis and Lung Diseases Research Institute, Warsaw Poland., Gorecka D; 2nd Department of Respiratory Medicine, National Tuberculosis and Lung Diseases Research Institute, Warsaw Poland., Demkow U; Laboratory Diagnostics and Clinical Immunology, Medical University of Warsaw, Poland., Sliwinski P; 2nd Department of Respiratory Medicine, National Tuberculosis and Lung Diseases Research Institute, Warsaw Poland.
Jazyk:	angličtina
Zdroj:	Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG [Sarcoidosis Vasc Diffuse Lung Dis] 2019; Vol. 36 (4), pp. 261-273. Date of Electronic Publication: 2019 May 01.
DOI:	10.36141/svdld.v36i4.7708
Abstrakt:	Introduction: Methotrexate therapy improves lung function in selected sarcoidosis patients. Variation in TNF gene was associated with response to treatment. Aim: To determine the predictive role of-308 G/A, -857C/T, -863 C/A and -1031 T/C TNF- α polymorphism in the efficacy of MTX for progressive pulmonary sarcoidosis. Material and Methods: Twenty-eight sarcoidosis patients treated with MTX (6-24 months) were genotyped for TNF- α polymorphisms: -1031 T/C, -857C/T, -308 G/A and -863 C/A. Pulmonary function test (PFT) were performed every 6 months to determine treatment response, until the drug withdrawal. Results: No correlation between the initial clinical presentation of sarcoidosis and TNF α polymorphisms was found, neither for every allele nor for combined genotypes distribution. According to PFT evaluation we have discovered 3 types of response to MTX: early (ER), late (LR) and No-response (NR). TNF- α-308 A allele carriers have got significantly higher chance to be LR, p=0.02, RRI:83%. TNF- α-308 GG genotype transferred the 3-fold higher probability of early vs late response to MTX, p=0.02. Combined genotyping allowed to distinguish LR from ER and NR groups. ER and NR patients are genetically similar (-857CC-308GG). LR are "genetically" different group of patients (-857C/T-308GG or -857CC-308A/G) with 5-fold greater probability to be LR than TNF- α-857CC-308GG patients, p=0,005 sensitivity 85%, specificity: 43%, PPV 58%, NPV 75%. TNF- α - 308GG-857CC patients have significantly lower chance to be LR comparing to other response type p=0.03 OR=0,075 95% CI=0.07-0.08. Conclusion: Two types of positive response to MTX therapy (early and late) in chronic respiratory sarcoidosis are associated with polymorphic changes in TNF gene. (Copyright: © 2019.)
Databáze:	MEDLINE
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