The HLA-DPB1--associated component of the IDDM1 and its relationship to the major loci HLA-DQB1, -DQA1, and -DRB1.

The major histocompatibility complex (MHC) HLA region on chromosome 6p21 contains the major locus of type 1 diabetes (IDDM1). Common allelic variants at the class II HLA-DRB1, -DQA1, and -DQB1 loci account for the major part of IDDM1. Previous studies suggested that other MHC loci are likely to contribute to IDDM1, but determination of their relative contributions and identities is difficult because of strong linkage disequilibrium between MHC loci. One prime candidate is the polymorphic HLA-DPB1 locus, which (with the DPA1 locus) encodes the third class II antigen-presenting molecule. However, the results obtained in previous studies appear to be contradictory. Therefore, we have analyzed 408 white European families (200 from Sardinia and 208 from the U.K.) using a combination of association tests designed to directly compare the effect of DPB1 variation on the relative predisposition of DR-DQ haplotypes, taking into account linkage disequilibrium between DPB1 and the DRB1, DQA1, and DQB1 loci. In these populations, the overall contribution of DPB1 to IDDM1 is small. The main component of the DPB1 contribution to IDDM1 in these populations appears to be the protection associated with DPB1*0402 on DR4-negative haplotypes. We suggest that the HLA-DP molecule itself contributes to IDDM1.

Conditional ETDT analysis of the human leukocyte antigen region in type 1 diabetes.

Several studies have indicated that additional genes in the major histocompatibility complex (MHC) region, other than the class II genes HLA-DQB1 and -DRB1 (the IDDM1 locus), may contribute to susceptibility and resistance to type 1 diabetes. The relative magnitude of these non- DR/DQ effects is uncertain and their map location is unknown owing to the extraordinary linkage disequilibrium that extends over the 3.5 Mb of the MHC. The homozygous parent test has been proposed as a method for detection of additional risk factors conditional on HLA-DQB1 and -DRB1. However, this method is inefficient since it uses only parents homozygous for the primary disease locus, the DQB1-DRB1 haplotype. To overcome this limitation, Conditional ETDT was used in the present report to test for association conditional on the DQB1-DRB1 haplotype, thereby allowing all parents to be included in the analysis. First, we confirm in UK and Sardinian type 1 diabetic families that allelic variation at HLA-DRB1 has a very significant effect on the association of DQB1 and vice versa. The Conditional ETDT was then applied to the HLA TNF (tumour necrosis factor) region and microsatellite marker D6S273 region, both of which have been reported to contribute to IDDM1 independent of the HLA-DQB1-DRB1 genes. We found no evidence for a major role for either of these two regions in IDDM1.

[The presence of nucleotide sequences of the hepatitis B virus in peripheral lymphocytes of patients with acute hepatitis B]. / Presenza di sequenze nucleotidiche del virus dell'epatite B nei linfociti periferici di pazienti con epatite acuta di tipo B.

Hepatitis B virus (HBV) DNA sequences were assessed in 26 patients with acute type B hepatitis, using dot-blot hybridization technique from peripheral blood mononuclear cells (PBMC), during different phases of the illness. At clinical presentation, 15% of patients showed HBV-DNA sequences in PBMC, while serum HBV-DNA was detected in 58% of patients. During clinical improvement 50% of patients had HBV-DNA in PBMC but only 11.5% were positive for serum HBV-DNA. Twenty-three (88.5%) patients recovered and cleared HBV-DNA from serum and from PBMC; three (11.5%) patients with acute hepatitis progressing to chronicity showed persistently HBV-DNA sequences in serum and in PBMC. In conclusion, our study shows that HBV-DNA sequences may be found in PBMC, transiently in patients with acute hepatitis followed by recovery, persistently in patients with acute hepatitis progressing to chronicity.