Major histocompatibility complex and tumor necrosis factor-alpha polymorphisms in pigeon breeder's disease

Pigeon breeders disease (PBD) is caused by the exposure of a susceptible ho st to avian antigens. However, genetic factors determining individual predi sposition are unknown. In this work, polymorphisms of the major histocompat ibility complex (MHC) class II alleles end tumor necrosis factor alpha (TNF -alpha) promoter were evaluated in 44 patients with PBD, 99 healthy unrelat ed controls (HC), and 50 exposed but asymptomatic subjects (EAS). MHC typin g was performed by PCR-specific sequence oligonucleotide analysis, and TNF- alpha polymorphism at -238 and -308 positions by amplification refractory m utation system-PCR. PBD patients showed a significant increase of the allel es HLA-DRB1*1305 (p < 0.001, OR = 15.4, 95%: CI = 3.18-102.6 [HC], and OR = 17.05, 95% Cl = 2.25-357.8 [EAS]) and HLA-DQB1*0501 (p < 0.05, OR = 2.93, 95% CI = 1.21-7.15 [HC], and OR = 2.96, 95% CL = 1.0-9.14 [EAS]). A decreas e of HLA-DRB1*0802 was also noticed in patients when compared: with both co ntrol groups (p < 0.05). Haplotype analysis revealed an increase of DRB1*13 05-DQB1*0301 and a decrease of DRB1*0802-DQB1*0402. PBD patients had an inc reased frequency of TNF-2(-308) compared with both control groups (p < 0.05 ). Patients exhibiting the TNF-2(-308) allele were younger (33.9 +/- 14.6 v ersus 44.2 +/- 70.4 yr; p < 0.05), and displayed more lymphocytes in their bronchoalveolar lavages (88.0 +/- 12.1 versus 68.9 +/- 17.2; p < 0.05). The se results suggest that genetic factors located within the MHC region contr ibute to the development of PBD.