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.