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

Main Article Content

Anna Goljan Geremek
Elzbieta Puscinska
Monika Czystowska
Agnieszka Skoczylas
Michal Bednarek
Adam Nowinski
Dorota Gorecka
Urszula Demkow
Pawel Sliwinski




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.


Download data is not yet available.
Abstract 269 | PDF Downloads 136

Most read articles by the same author(s)