Am. J. Respir. Crit. Care Med., Volume 163, Number 7, June 2001, 1528-1533

Major Histocompatibility Complex and Tumor Necrosis Factor- Polymorphisms in Pigeon Breeder's Disease

ANGEL CAMARENA, ARMIDA JUÁREZ, MAYRA MEJÍA, ANDREA ESTRADA, GUILLERMO CARRILLO, RAMCÉS FALFÁN, JOAQUÍN ZUÑIGA, CARMEN NAVARRO, JULIO GRANADOS, and MOISÉS SELMAN

Instituto Nacional de Enfermedades Respiratorias, Tlalpan 4502, México DF, México; and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, México DF, México

Pigeon breeders disease (PBD) is caused by the exposure of a susceptible host to avian antigens. However, genetic factors determining individual predisposition are unknown. In this work, polymorphisms of the major histocompatibility complex (MHC) class II alleles and tumor necrosis factor alpha (TNF-) promoter were evaluated in 44 patients with PBD, 99 healthy unrelated controls (HC), and 50 exposed but asymptomatic subjects (EAS). MHC typing was performed by PCR-specific sequence oligonucleotide analysis, and TNF- polymorphism at 238 and 308 positions by amplification refractory mutation system-PCR. PBD patients showed a significant increase of the alleles HLA-DRB1*1305 (p < 0.001, OR = 15.4, 95% CI = 3.18-102.6 [HC], and OR = 17.05, 95% CI = 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% CI = 1.0-9.14 [EAS]). A decrease of HLA-DRB1*0802 was also noticed in patients when compared with both control groups (p < 0.05). Haplotype analysis revealed an increase of DRB1*1305-DQB1*0301 and a decrease of DRB1*0802-DQB1*0402. PBD patients had an increased frequency of TNF-2³⁰⁸ compared with both control groups (p < 0.05). Patients exhibiting the TNF-2³⁰⁸ allele were younger (33.9 ± 14.6 versus 44.2 ± 10.4 yr; p < 0.05), and displayed more lymphocytes in their bronchoalveolar lavages (88.0 ± 12.1 versus 68.9 ± 17.2; p < 0.05). These results suggest that genetic factors located within the MHC region contribute to the development of PBD.

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