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Biomedical subjects

E Maruya

Publications and source records attributed to E Maruya.

10 recordsLinked to original sources

HLAs and genes in Japanese patients with multiple sclerosis: evidence for increased frequencies of HLA-Cw3, HLA-DR2, and HLA-DQB1*0602.

The distribution of HLA-A, B, C, DR and DRB1, DQB1, DPB1 alleles was studied in 60 Japanese patients with clinically definite multiple sclerosis (MS) using serologic and genomic analysis. We found significant associations with HLA-Cw3 (p = 0.002, pc = 0.012, RR = 3.2), DR2 (p = 0.007, RR = 2.6), and DQB1*0602 (p = 0.04, RR = 4.0) in Japanese patients for the first time. The combined presence of Cw3 and DR2 gave a higher risk than each antigen alone. The reported increase in the frequency of DPw4 in Japanese MS patients [12] could not be confirmed by our genomic study. The frequencies of all of the residues in each variable region of the amino acid sequences of DQ beta and DP beta chains were not different between the MS patients and the controls. These results suggest that MS susceptibility may result from polygenic influences and from the presence of environmental factors.

Alleles

Human platelet-specific antigen, Siba, is associated with the molecular weight polymorphism of glycoprotein Ib alpha.

Platelet-specific antigen Sib(a) has been highly implicated in the pathogenesis of refractoriness to human leukocyte antigen (HLA)-matched platelet transfusions in Japan. We provide evidence that the Sib(a) antigen is located on the glycoprotein (GP) Ib alpha and has a close association with the molecular weight (mol wt) polymorphism of GPIb. In modified antigen-capture ELISA (MACE), anti-Sib(a) antibody reacted only with GPIb/IX held by a murine anti-GPIb/IX monoclonal antibody (MoAb). The reactivity of anti-Sib(a) antibody to Sib(a)-positive (Sib(a+)) platelets was abolished after they were treated with Serratia marcescens protease. Platelets from 50 healthy volunteers were semiquantitatively phenotyped for Sib(a) antigen by MACE and divided into three distinct groups: strongly positive, positive, and negative. They were also analyzed by sodium dodeyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and periodic acid-silver staining for mol wt polymorphism of GPIb, phenotyped as A, B, C, or D. Without exception, Sib(a+) platelets showed larger phenotypes (A or B). Removal of sialic acid from Sib(a+) platelets did not reduce the binding of anti-Sib(a). Finally, anti-Sib(a) antibody specifically immunoprecipitated A and B phenotypes of GPIb from Sib(a+) platelets. Thus, Sib(a) antigen evidently is located in the region of glycocalicin that is present only on the A and B phenotypes of GPIb.

Antigens, Human Platelet

Postoperative erythroderma with change of HLA phenotypes from heterozygotes to homozygotes: a report of two cases.

Fatal "postoperative erythroderma" (POE) developed in 2 patients treated with liver lobectomy and the transfusion of fresh blood. Their clinical features and skin-histological findings were indicative of acute graft-versus-host disease (GVHD). The HLA phenotypes of circulating lymphocytes of the 2 patients were heterozygous but became homozygous late in the clinical course and were identical with those of the blood donors. One of the patient's haplotypes was identical with the donor's homozygous haplotype. These findings suggest the mechanism of development of POE in apparently immunocompetent patients. The donor's T lymphocytes are histocompatible with the patient's tissues, are not rejected, and become engrafted. The patient's tissues are not histocompatible with the donor's, so that GVHD develops.

Blood Donors

Heterogeneity of non-insulin-dependent diabetes mellitus in HLA types and clinical features: comparison with insulin-dependent diabetes mellitus.

We determined HLA types in 110 Japanese patients with non-insulin-dependent diabetes mellitus (NIDDM) and studied the relationship between the HLA phenotypes and clinical features. Sixty-nine patients with insulin-dependent diabetes mellitus (IDDM) and 100 healthy blood donors served as controls. Concerning HLA DR and DQ loci, frequencies of DR4, DRw9 and DQw3.2 were higher, and those of DR2, DRw8, DRw11, DRw12 and DQw1 were lower in patients with IDDM compared than in healthy controls. There were no differences between NIDDM and normal controls in the frequency of a particular HLA DR antigen except for a decreased frequency in DRw11 in the former. The frequency of DQw3.2 antigen in NIDDM was intermediate between IDDM and normal controls. There were some differences between DQw3.2-positive and -negative NIDDM patients in clinical features. Those who showed low C-peptide responses during oral glucose tolerance test were more frequently found among DQw3.2-positive NIDDM patients. These results suggest that Type 1 diabetes mellitus may have a mild clinical course and is found among the Japanese NIDDM population.

Age Factors

HLA class I epitopes accounted for by single residues.

We examined the serological reaction of 50,000 HLA antisera for correlations with amino acid substitutions at 16 variable residues on the A locus and 8 variable residues on the B locus. We identified antisera that produced mutually exclusive allelic reactions corresponding to amino acid variants at the various residues. We assumed that by this procedure, epitopes that were determined by a single amino acid substitution could be identified. Among 55 variable residues on the A locus, antibodies that reacted in an allelic fashion were found for 16, or 32%. These serologically determined epitopes were on the alpha helix for 13 of the 16 residues, and 3 were in the beta sheet. Among 54 variable residues for the B locus, antibodies were found to 8 which reacted in a mutually exclusive pattern. Thus, 13% of the residues were serologically defined. Sixteen "monospecific" HLA specificities were determined by a single residue. Interestingly, many "multispecific" sera could be accounted for by reactions to a single amino-acid defined epitope. We assume that most of the other monospecific and multispecific specificities are determined by conformational epitopes, as described in an accompanying article (Ch. 33).

Alleles

New platelet antigen, Siba, involved in platelet transfusion refractoriness in a Japanese man.

Siba, a new platelet-specific alloantigen involved in a case of platelet transfusion refractoriness is reported. The IgG platelet alloantibody was detected in a multiply transfused patient of Japanese extraction (Sib), by the presence of HLA antibodies. After transfusion of HLA-compatible platelets, the patient suffered from refractoriness. Adsorption studies with pooled lymphocytes showed that the serum contained anti-platelet activity. Family studies indicate that Siba is inherited as an autosomal codominant trait and separate from HLA and Baka. As of this report, segregation from Zw(PlA) and Yuk (Pen) antigen systems have not yet been determined. The gene frequency of Siba in the Japanese population is estimated to be 0.136.

Antibody Specificity