Effect of genotype on hypersensitivity pneumonitis despite treatment.

The aim of presented study was to show possible effect of genotype on disease course in hypersensitivity pneumonitis (HP) patients with dominant fibrotic lung involvement. Nineteen consecutive HP patients were enrolled into the study. Diagnosis of HP was assessed multidisciplinary (history, exposure, radiographic, bronchoalveolar lavage and (if available) histopathology). Patients lung functions were reconcilled after 6, 12 and 18 months. Progression of HP was defined as either drop of FVC ˃10 % or/and drop of DLco ˃15 % and/or acute exacerbation and/or death in 6 months period. Percentages of change in FVC/DLco were counted from the absolut value of previous result. Blood sample for DNA analysis was assessed, DNA isolated, panel of SNPs in the genes as candidate loci in HP susceptibility were selected. Selected SNPs were investigated using MALDI-TOF MS based MassARRAY (Agena Bioscience) or TaqMan (Life Technologies) genotyping assays. Fisher exact test (2-tail) was used for statistical analysis. We found no effect of investigated gene polymorphisms on outcome of patients within enrollment up to twelve months observational period. Eighteen months after diagnosis effect of TOLLIP SNP (rs111521887) on patients outcome was observed (risk alele T, p=0,031). Relative risk of progression was found in patients TOLLIP SNP (rs5743894) with CG genotype (alele CC was found to be protective), OR 16,0 (95 % CI 1,1-234,3, p=0,04). Significant effect of TOLLIP (rs5743890) on patients outcome was detected (risk alel CT, OR 6,0 (95 % CI 0,87-41,4, p=0,07)). It is highly probable, that genetics may not only affect the probability of HP development in patient´s lifecourse, it may also play role in patient´s prognosis.