Restriction fragment length polymorphism analysis in the HLA class III genes of patients with diffuse panbronchiolitis

Abstract

Although diffuse panbronchiolitis (DPB) is known to be positively associated with certain major histocompatibility complex (MHC) class I antigens, e.g., HLA-B54 in Japanese patients, it is not clear whether the MHC genes predispose to the disease or are markers for other disease susceptibility gene(s). Because the HLA class III genes such as tumor necrosis factor (TNF) or the fourth component of complement (C4) are localized in the proximity of the HLA-B locus, one or more of these genes might be responsible for susceptibility to DPB. To analyze the role of HLA class III genes in DPB patients, we first evaluated the HLA-B54 association in 32 patients with DPB, and subsequently, studied the restriction fragment length polymorphism (RFLP) of the TNF-alpha and -beta (TNF-alpha/beta) genes as well as the C4A and B (C4A/B) genes in DPB patients and normal individuals. The HLA-B54 antigen was significantly more frequent in DPB patients than in normal individuals (40.3% vs 13.0%, p < 0.001), however, we did not detect a significant association between DPB and gene polymorphisms of either TNF-alpha/beta or C4A/B. Furthermore, there was no evidence of C4A gene deletion in patients with DPB. These results suggest that the HLA-B54 antigen itself might be directly involved in the pathogenesis of DPB.