Yasutaka Ina, MD; Katsutoshi Takada...

Yasutaka Ina, MD; Katsutoshi Takada, MD; [unkeyable] Masahiko Yamamoto, MD FCCP; [unkeyable] Munehiko Morishita, MD; [unkeyable] Yoshihiro Senda, MD; and Yoshio Torii, MD

individual hundred fourteen patients with sarcoidosis, who were diagnosed as having sarcoidosis histologically, have been typ for HLA class 1 (A, B and C) and class 2 (DR and DQ) antigens. masterys consisted of 478 healthy Japanese exposes The frequencies of HLA-A1, HLA-Bw46, HLA-Cx46, HLA-DRw8, HLA-DRw9, and HLA-DRw52 were significantly increased in sarcoidosis compared to command subjects, but only four patients were positive for HLA-A1. Increased frequencies of HLA-Bw46 and HLA-Cx46 were throught to be attributable to linkage disequilibrium with HLA-DRw8. Patients with HLA-DRw52 were the mostly frequent (84 cases of 113) No significant differences were observ between HLA-DRw52-positive and HLA-DRw52-negative patients in their clinical features, yet all of the patients with muscular involvement (six cases) were positive for HLA-DRw52. Among patients positive for HLA-DRw52, those with HLA-DR5 showed a significantly better clinical course and earlier charge of the disease than those with HLA-DRw8. These outcomes suggest that HLA antigens may play an important part in the pathogenesis of sarcoidosis. (Chest 1989; 95:1257-61)

HLA = human leukocyte antigen; RR = relative risk; pc = corrected p value

Sarcoidosis is a disease of unknown etiology characterized according to the presence of noncaseating epitheloid solitary abode; squalid granulomas in various organs and several immunologic disorders.[1-3] There is increasing evidence that gene coding for certain HLA antigens are closely associated genetic determinants of the susceptibility to specific diseases in humans; examples include myasthenia gravis,[4] ankylosing spondylitis,[5] narcolepsy,[6] and lupus erythematosus.[7] Although frequencies of HLA class 1 antigens in patients with sarcoidosis have thus far been reported in order to account for the immunogenetic factor in the pathogenesis of sarcoidosis,[8-12] those of HLA class 2 antigens have been seldom reported.[13,14]

Therefore, we determined whether there was a specific association between HLA antigens and sarcoidosis, with the be derived that a significant association of sarcoidosis with HLA-DRw8, HLA-DRw9, and HLA-DRw52 was demonstrated. Thus, a further investigation was undertaken to determine whether there was any significant association between HLA-DR antigens and clinical features of Japanese sarcoidosis.

MATERIALS AND METHODS

single hundred and fourteen patients with sarcoidosis who were available for HLA typing were included in the existing study. There were 41 male and 73 female patients, with an average age of 458 [+ or -] 158 years ([+ or -] SD) at attack Sarcoidosis was diagnosed forward the basis of the clinical picture, plus the demeanor of epithelioid cell granuloma in succession the biopsy specimen of the involved tissue, with the involved tissue being either lung skin, or lymph node. The chest roentgenographic findings were classified into three stages as defined by the agency of Wurm and Heilmeyer.[15] There were 64 patients in stage 1; in stage 2 there were 29 patients, and there were six in stage 3

Involvement of the vigilances was observed in 68 percent (77/114) and muscular involvement in 5 percent (6/114) of the near patients. Muscular involvement included five cases with palpable nodules and common case with myopathy. None was receiving steroids.

Four hundr and seventy-eight age-matched and sex-matched Japanese enthralls served as controls. All of them were either vital fluid donors or kidney donors visiting the Nagoya next to the first Red Cross Hospital and were confirmed to be exempt from any diseases

solitary abode; squalid Preparation

Lymphocytes were separated from heparinized venous family by means of centrifugation in Ficoll/Isopaque. B-lymphocyte were separated on the thrombin-nylon wool method(16) and then were used to original for HLA class 2 (DR and DQ) antigens. T-lymphocyte were used for HLA class 1 (A, B and C) antigen typing.

HLA Typing

The HLA typing was performed by the agency of the standard NIH complement-dependent microcytotoxicity proof as described previously.[16]

Statistics

The HLA data were analyzed for significance from the [X.sup.2] test. The p values obtained were corrected through multiplying by the number of antigens determined at the locus (pc) The relative risk (RR) was calculated by dint of the formation of Woolf as modified at Haldane.[17]

RESULTS

The oftenness of HLA class 1 antigens is listed in Table 1 Among HLA class 1 antigens, HLA-A1, HLA-B37, HLA-Bw46, HLA-Cw6, and HLA-Cx46 were significantly more visit often in sarcoidosis than in govern subjects; however, HLA-B37 and HLA-Cw6 were not significant when corrected p was applied, and the number of patients positive for HLA-A1 was alone four, a number too small to cogitation statistically. Among HLA class 2 antigens, HLA-DRw8, HLA-DRw9, and HLA-DRw52 were significantly higher in sarcoidosis than in repress subjects, even when corrected p was applied. in succession the other hand, there was no significant difference in HLA-DQ antigens between the brace groups (Table 2).