Different contribution of class II HLA in fulminant and typical autoimmune type 1 diabetes mellitus.

AIMS/HYPOTHESIS: Fulminant type 1 diabetes, which is characterised by a markedly acute onset of diabetes and an absence of islet-related autoantibodies, accounts for 20% of type 1 diabetes in Japan. We aimed to clarify the contribution of the HLA subtype to fulminant type 1 diabetes in Japanese. METHODS: We determined the serological subtypes of HLA-A, -DR and -DQ in 115 patients with fulminant type 1 diabetes, 98 patients with typical type 1A diabetes and 190 normal control subjects. RESULTS: The frequency of HLA-DR4, but not DR9, was significantly higher in fulminant type 1 diabetes, while those of HLA-DR1, DR2, DR5 and DR8 were significantly lower than those in controls. In contrast, DR9 but not DR4 was more frequent and DR2 was extremely rare in typical type 1A diabetes. Haplotype analysis revealed that DR4-DQ4 was significantly more frequent, and both DR2-DQ1 and DR8-DQ1 were less frequent in fulminant diabetes. In type 1A diabetes, DR2-DQ1 was extremely rare while DR9-DQ3 was significantly more frequent. In the combination analysis, the homozygotes of DR4-DQ4 in fulminant type 1 diabetes and DR9-DQ3 in typical type 1A diabetes indicated high odds ratios (13.3 and 13.3, respectively). CONCLUSIONS/INTERPRETATION: Our results suggest that class II HLA contributes to the development of fulminant type 1 diabetes. Susceptibility and resistance of the HLA subtype to type 1 diabetes are distinct between fulminant and typical autoimmune type 1 diabetes.

Expression of TRAIL, DR4, and DR5 in kidney and serum from patients receiving renal transplantation.

Renal transplantation is the best treatment of some end-stage renal diseases. Unfortunately, not every transplant is successful due to the rejection or dysfunction of the transplanted kidney. Many cytokines participate in rejection by inducing inflammation or apoptosis. In this study, the expressions of TRAIL, DR4, and DR5 in rejected renal tissue and of serum soluble TRAIL (sTRAIL) in patients with kidney rejection were investigated by immunohistochemical staining and sandwich enzyme-linked immunosorbent assay, respectively. The results showed that the expression of TRAIL, DR4 and DR5, and serum sTRAIL levels were markedly upregulated among renal transplant patients. Since both membrane and soluble forms of TRAIL can induce apoptosis of DR4/DR5-expressing cells via recruiting FADD and caspase 8, elevated TRAIL and its receptors may participate in renal graft rejection.

A common HLA phenotype in slipped capital femoral epiphysis?

Studies from three different countries have linked the HLA B12 and DR4 antigens with slipped capital femoral epiphysis (SCFE). We questioned whether our patients shared in common either of these antigens. HLA phenotype was determined in 7 patients with SCFE, two of whom were brothers with almost identical haplotypes. The B12 antigen was found in none of our patients and the DR4 in only 3. Neither of the 2 brothers held the DR4 antigen. The commonest antigens (also shared by the 2 brothers) were B35, present in 5 and DR52 in 4 of 7 patients. We conclude that neither the previously described B12 nor the DR4 antigen can reliably serve as genetic markers for SCFE in our region.

HLA antigens in Arabs with lichen planus.

We have HLA typed 50 Arab patients with cutaneous lichen planus who were resident in Kuwait and then compared the antigen incidence with 100 normal controls. There were no significant differences in the antigens of the HLA-ABC loci but there was a significant increase in HLA-DR1 (P = 0.0018, RR = 3.68) and HLA-DR10 (P. corr. = 0.00096, RR = 8.27) and a significant decrease in HLA DR5 (P. corr. = 0.0396, RR = 0.18). The relevance of these findings to earlier reports on lichen planus in which HLA-DR1 (but not DR10) is increased is discussed. This is the first report of HLA antigen frequency in Arab patients with lichen planus, and would support the fact that HLA DR1 is universally associated with the disease, although the more significant association appears to be with HLA-DR10.

Histocompatibility antigens and geographic tongue.

The HLA-A, B and HLA-DR antigens were investigated in 50 unrelated Greek persons with geographic tongue and in 380 healthy control persons. An increased incidence of DR5 and DRW6 antigens was observed in the blood of persons with geographic tongue. Ten (20%) of them had the DRW6 antigen, and it was significantly increased compared with 29 (7.6%) of the controls (p < 0.01, RR = 3.32). Twenty-seven (54%) of the experimental group showed DR5 antigen compared with 136 (35.7%) of the controls (p < 0.025, RR = 2.18). On the contrary, only 12% (5) of the experimental group had the B51 antigen in comparison with the controls (26.3%) (p < 0.05, RR = 0.37). A decrease of the DR2 antigen was also found in the persons with geographic tongue (24%) in comparison with the controls (39.2%) (p < 0.05, RR = 0.58).

HLA-DR3 and HLA-DR5 confer risk for autoantibody positivity against the thyroperoxidase (mic-TPO) antigen in healthy blood donors.

The prevalence of circulating autoantibodies against thyroperoxidase (mic-TPO) was determined in 3,000 healthy blood donors (age range: 23 to 60 years) from the Hamburg area. Of the blood donors, 153 (5.1%) were found to have high titer of mic-TPO (> 350 IU/ml). Only two autoantibody positive subjects (0.06%) were chemically hyper- and hypothyroid, respectively. Analysis of HLA-DR specificities revealed that HLA-DR specificities DR3 and DR5 were significantly increased when compared to controls (n = 1,863). Comparison of the autoantibody-positive probands with a group of disease controls, i.e., Graves' patients and patients with lymphocytic thyroiditis, revealed a higher prevalence of HLA-DR3-positive HLA haplotypes in the disease controls when compared to autoantibody positives. Individuals with a mic-TPO level greater than 2,000 IU/ml were almost exclusively found to have one HLA-DR3 or HLA-DR5 positive HLA haplotype. We conclude that a high prevalence of high-titer mic-TPO can be found in healthy blood donors. Circulating signs of thyroid autoimmunity were associated with HLA specificities also found to be associated with autoimmune thyroid diseases.

[Effect of HLA- genotype on bacterial colonization and antigenemia in patients with infiltrative pulmonary tuberculosis]. / Vliianie HLA-genotipa u bolnykh infiltrativnym tuberkulëzom lëgkikh na bakterialnuiu populiatsiiu i antigenemiiu.

150 patients with infiltrative tuberculosis (IT) and 135 healthy subjects were subjected to HLA-typing. Clinico-immunogenetic correlations provided evidence for significantly higher incidence of antigens A11, B12, Cw2, DR2, DR5 in IT patients versus healthy subjects. Antigens Cw3 and DR2 occur more frequently in progressive disease. IT patients disseminating M. tuberculosis carry more frequently antigens HLA-DR2, those with L-forms DR5, with antigenemia antigens HLA-DR2 and DR4.

HLA-DR/DQ gene variation in nongoitrous autoimmune thyroiditis at the serological and molecular level.

The etiology of autoimmune diseases is multifactorial with genetic factors being an important prerequisite. There are two clinical manifestations of autoimmune thyroiditis: the goitrous form (Hashimoto's thyroiditis) and the atrophic variant, which is characterized by hypothyroidism (primary myxoedema). Different genetic markers were assumed to be predisposing factors for the distinct clinical presentation. In the present study, we determined HLA A,B,C,DR,DQ alloantigens serologically and HLA-DQ by gene analysis in patients with nongoitrous autoimmune thyroiditis and randomly chosen controls. To verify the exact classifications, thyroid volume (median 5.85 ml) was measured by ultrasonography. HLA-DR5 was found in 16 of 36 (44%) patients with nongoitrous autoimmune thyroiditis and in only 26 of 175 controls (15%) (Pc = 0.0018). There was a tendency towards a lower frequency of HLA-DR7 with 6% positivity in patients vs. 29% in controls (Pc = 0.052). Regarding HLA-DQ, DQ7 was found in 17 of 35 patients (48%) vs. 21 of 98 controls (21%) (Pc = 0.028) (relative risk 3.5). No other association was found with HLA-A,B,C and HLA-DR and -DQ. Our data indicate that the genetic susceptibility to autoimmune nongoitrous thyroiditis is closely associated to HLA-DR5 and DQ7 and not distinct from goitrous disease. We conclude that factors other than genetic ones explain the different immunological and clinical manifestation of chronic lymphocytic thyroiditis.