Contribution of HLA Genes to Genetic Predisposition in Diffuse Panbronchiolitis

Abstract

Diffuse panbronchiolitis (DPB) in East Asia is a distinctive chronic obstructive pulmonary disease of unknown etiology. We hypothesize that the disease susceptibility is due to genetic predisposition unique to Asians. Association between human leukocyte antigen (HLA)-Bw54 and the disease was previously reported. In the present study, using newly developed polymerase chain reaction (PCR)- based methods, we directly analyzed HLA class I and II alleles in 76 Japanese patients. HLA-A, -B, and -C antigens were screened by the conventional typing method, and then B22-group alleles including HLA-B54 were genotyped by single-strand conformation polymorphism analysis. Alleles of HLA-DRB1 gene were fully determined by the microtiter plate hybridization method. Thirty-seven percent of the patients possessed HLA-B*5401 allele conserved predominantly in East Asians, as compared with 15% of 110 healthy volunteers (chi2 = 12.4, p = 0.0004). In addition, 4% of the patients possessed B*5504 also unique to Asians but a rare allele which was not found in normal control subjects in this study. Typing of HLA-DRB1 class II gene did not demonstrate strong positive association with the disease. A33, B44, and DRB1*1302 showed negative association with the disease. We conclude that distinctive molecular structure of HLA-B alleles or a closely linked gene in the HLA region contributes to genetic predisposition in diffuse panbronchiolitis. This may partly explain why this disorder is found primarily in Asians.

Effect of Azithromycin on Patients with Diffuse Panbronchiolitis: Retrospective Study of 51 Cases

“…However, the cold hemagglutinin (CHA) titer was only 17.6% of positive in our DPB patients, suggesting that the CHA titer might not be as important for the diagnosis of Chinese DPB patients as it for Japanese (27,43). Additionally, positive HLA-BW54 was only detected in 3 of 12 (25.0%) patients in this group, suggesting that the relationship between HLA-BW54 and Chinese DPB patients might not correlate as well as with Japanese DPB patients (44). Among diagnostic tests, a chest CT scan provides the most valuable diagnostic means for such patients.…”

The Influence of HLA Class I Alleles and Heterozygosity on the Outcome of Human T Cell Lymphotropic Virus Type I Infection

“…Hatta et al (60) have recently suggested that this B*54-associated haplotype is particularly common in the Ryukyuan population, who form one of the important ancestral populations of Okinawa and Kyushu in Southern Japan. Associations have also been described between B*5401 and other inflammatory conditions in Japan, including hepatitis C (61, 62) and diffuse panbronchiolitis (63,64). The HLA-associated susceptibility gene associated with diffuse panbronchiolitis has been mapped to a 200-kb region, 300 kb telomeric of the HLA-B locus (65).…”

Association of Gc-globulin variation with susceptibility to COPD and diffuse panbronchiolitis

“…Blood samples of the DPB cases were obtained from the Toranomon Hospital, Tenri Hospital, or Nippon Medical School Hospital, Japan. The diagnostic criteria for DPB proposed in 1995 by a working groups [9] were: 1) persistent cough, sputum, and exertional dyspnoea; 2) past or present history of chronic sinusitis; 3) bilateral diffuse small nodular shadows on a plain chest radiograph film or centrilobular micronodules on chest CT images; 4) coarse crackles; 5) FEV1/FVC v70% and oxygen tension in arterial blood v10.64 kPa (v80 mmHg); and 6) titre of cold haemagglutinin ¡64. A total of 82 DPB patients were recruited for this study and fulfilled criteria 1), 2), 3) and at least two of criteria 4), 5), and 6).…”

“…Cases of DPB are mainly found in East Asian populations [7,8], and neither environmental factors nor infections specific to the disease have been demonstrated. It has also been reported that human leukocyte antigen-B alleles or a closely linked gene contribute to genetic predisposition in DPB [9]. After considering these facts, the authors hypothesized that genetic factors may be associated with the pathogenesis of DPB.…”