TNF-α polymorphism as a prognostic marker for MTX efficacy in progressive pulmonary sarcoidosis

MTX therapy may improve lung function in patients with chronic progressive pulmonary sarcoidosis. Individual response to therapy may depend on gene polymorphism. TNF-α is a key cytokine in pathogenesis of granuloma formation. Variation in TNF gene was associated with response to TNF inhibitors in sarcoidosis. Aim: to define the clinical utility of TNF-α polymorphism assessment as a predictor of MTX treatment for pulmonary sarcoidosis. Material and methods: 27 out of 52 patients with chronic progressive pulmonary sarcoidosis treated with MTX were genotyped for the presence of the following TNF-α polymorphisms: -1031 T/C , -857C/T , -308 G/A and -863 C/A. . Treatment response (10% improvement in FEV 1 , FVC, TLC or 15% in DLCO from the initial value) was assessed after 6 months (early responders), and at the end of therapy, after 15-24 months (late responders). Patients who did not fulfill criteria of PFT improvement were classified as non-responders. Results: Presence of both -308G/A and -857 C/T polymorphisms were associated with response to MTX therapy (specifity 43%, sensitivity 85%, PPV 58%, NPV 75%.) Presence of-308 G/A polymorphism was associated with late response to MTX. No correlation with MTX efficacy was found for other TNF- α gene polymorphisms. Conclusion : The presence of -308 G/A and -857 C/T polymorphisms of TNF- α gene may indicate at favorable outcome of MTX therapy in pulmonary sarcoidosis.