Noboru Nabeya

HLA DPB1*0201 gene confers disease susceptibility in japanese with childhood onset type I diabetes, independent of HLA-DR and DQ genotypes.

HLA is an important etiologic genetic factor in Type I diabetes and specific HLA-class II genes are closely related to the onset of the disease. Many differences in the patterns of susceptible and resistant DRB1, DQA1, and DQB1 genes have been observed among various ethnic groups. We have previously shown that DRB1*0405, DRB1*0901 and DQA1*0301-DQB1*0302 were the major susceptible alleles or haplotype to Type I diabetes while DR-DQ haplotype studies suggested the important role of DR and DQ alleles in susceptibility and resistance in Japanese patients. Based on the analysis of 90 Japanese patients with childhood onset Type I diabetes and 136 unrelated healthy Japanese controls by polymerase chain reaction-restriction fragment polymorphism method (PCR-RFLP), we report here the association of Type I diabetes with DPB1*0201 (relative risk = 2.29; Pc = 0.027) in this population. Comparison of linkage disequilibrium patterns between patients and controls showed that the significantly high prevalence of DPB1*0201 among patients cannot be attributed simply to linkage disequilibrium with susceptible DRB1 alleles and DQA1-DQB1 haplotypes. Our results suggest that in addition to alleles at the DRB1, DQA1, DQB1 loci, polymorphism at DPB1 locus also influences the risk of Type I diabetes.

HL-A and hypertrophic cardiomyopathy

HL-A antigens were determined in 26 unrelated Japanese patients with hypertrophic cardiomyopathy. Several antigens were more common in patients compared with controls, but statistically significant differences were not evidenced. We also studied two families in which many had a hypertrophic cardiomyopathy. All the affected individuals revealed HL-A-A9 and B7, while none among the unaffected family members had HL-A-B7. Our findings suggest that the HLA-A system may play some role in the pathogenesis of hypertrophic cardiomyopathy with familial occurrence.

Islet cell antibodies in the Japanese population and subjects with Type 1 (insulin-dependent) diabetes

SummaryIslet cell antibodies were studied in 1,112 non-diabetic adults, 473 normal school children and 162 Type 1 (insulin-dependent) diabetic patients in a Japanese population. The prevalence of islet cell antibodies was 0.5%, 0.4% and 32%, respectively. Most islet cell antibodies positive subjects with Type 1 diabetes had short duration of the disease. No patients who had over 10 years from the onset had islet cell antibodies. Six non-diabetic adults with islet cell antibodies were followed for 4 years. Only one with Hashimotos thyroiditis showed a diabetic pattern in her oral glucose tolerance test. However, none developed overt insulin-dependent diabetes until 1984. Two out of these six subjects continued to be positive for both islet cell antibodies and antithyroid antibodies or antinuclear antibodies. Islet cell antibodies in the remaining four patients disappeared during the second year. It is difficult to predict the onset of Type 1 diabetes by islet cell antibodies in non-diabetic individuals because they may be transient.

Antibodies to Coxsackie B viruses and HLA in Japanese with juvenile-onset Type 1 (insulin-dependent) diabetes mellitus

SummaryOne hundred and three patients with juvenile-onset Type 1 (insulin-dependent) diabetes mellitus have been studied for evidence of previous Coxsackie B virus infection and compared with age- and sex-matched controls. Coxsackie B4 or B3 neutralization titre ⩾ 80 were more common among the patients than among the control subjects, but showed no association with HLA-B phenotypes.

Thyroid autoantibodies, antinuclear factors and HB antigen in various hepatic diseases

最近我が国では抗甲状腺抗体の検出法としてタンニン酸処理赤血球凝集反応を応用したThyroid test,及びMicrosome testがキット化され安定した成績が得られるようになってきた.そこで今回,われわれは正常健康人2,350名を対照とし各種肝疾患患者150名につきThyroid test及びMicrosome testを施行し同時に抗核抗体,HB抗原を検索し,これらの関連について検討した.その結果ルポイド肝炎では他の肝疾患に比し抗甲状腺抗体及び抗核抗体の両方共33.3%と著しく高い陽性率を示した.HB抗原は急性肝炎で35%と最も高い陽性率を示したが抗甲状腺抗体とHB抗原との間には相関する関係は見られず,また明らかな相互離反の傾向も見られなかった.抗甲状腺抗体と抗核抗体との間には明らかに相関する関係が見られた.抗甲状腺抗体は正常健康者と同じく肝疾患全体では男性よりも女性で2倍以上の陽性率を示したが10×28以上の高い抗体価を有する者は1例もなかった.

Thyroglobulin and microsomal antibodies in diabetes mellitus in childhood

The purpose of our study was to determine the incidence of thyroid antibodies in diabetes mellitus in childhood and to discuss the correlation between thyroid antibodies and insulin antibodies. The sera of 50 children with diabetes mellitus and 437 children as disease controls were tested by thyroglobulin and microsome-coated tanned red cell hemagglutination test (Fuji Zoki Co. Tokyo). One of the 50 children with diabetes mellitus (2%) was positive with antithyroglobulin antibodies and eleven (22%) were positive with antimicrosomal antibodies compared to 0.4% and 1.1% respectively in 437 disease controls. To clarify the association of insulin antibodies and thyroid antibodies in diabetes mellitus in childhood, insulin antibodies were demonstrated by using a modified method described by Wright. One of the 33 children with negative insulin antibody (2.8%) was positive with antithyroglobulin antibodies and eight (24%) were positive antimicrosomal antibodies. No evident correlation was observed between antithyroid antibodies and insulin antibodies.

Rheumatoid factor in diabetes mellitus

: This study was undertaken to try to determine the incidence of rheumatoid factor in patients with diabetes mellitus by the Hyland RA slide test and the RAHA test (the sensitized sheep red cell agglutination test). Sera from 507 patients with diabetes mellitus and 2073 controls were investigated for the presence of rheumatiod factors. RA test was positive in 8.7 per cent and RAHA test in 6.1 per cent in sera from patients with diabetes mellitus compared to 4.1 percent and 3.6 per cent respectively in healthy subjects.