RESTRICTION-FRAGMENT-LENGTH-POLYMORPHISM ANALYSIS IN THE HLA CLASS-III GENES OF PATIENTS WITH DIFFUSE PANBRONCHIOLITIS

Although diffuse panbronchiolitis (DPB) is known to be positively asso ciated with certain major histocompatibility complex (MHC) class I ant igens, 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 l ocalized in the proximity of the HLA-B locus, one or more of these gen es might be responsible for susceptibility to DPB. To analyze the role of HLA class III genes in DPB patients, we first evaluated the HLA-B5 4 association in 32 patients with DPB, and subsequently, studied the r estriction fragment length polymorphism (RFLP) of the TNF-alpha and -b eta (TNF-alpha/beta) genes as well as the C4A and B (C4A/B) genes in D PB patients and normal individuals. The HLA-B54 antigen was significan tly more frequent in DPB patients than in normal individuals (40.3% vs 13.0%, p<0.001), however, me 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 w ith DPB. These results suggest that the HLA-B54 antigen itself might b e directly involved in the pathogenesis of DPB.