Different contribution of HLA‐DR and ‐DQ genes in susceptibility and resistance to Insulin‐dependent diabetes mellitus (IDDM)

Yasunaga, Shin’ichiro; Kimura, Akinori; Hamaguchi, Kazuyuki; Rønningen, Kjersti S.; Sasazuki, Takehiko

doi:10.1111/j.1399-0039.1996.tb02512.x

Cited by 104 publications

(78 citation statements)

References 75 publications

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“…In AA patients carrying DRB1*1501, certain antigens of which presentation requires position 86 of the beta-chain to be glycine may likely induce an immune system attack to hematopoietic progenitor cells. It is also possible that DRB5*0101 and DRB5*0102, which are in complete linkage disequilibrium with DRB1*1501 and DRB1*1502, respectively, in the Japanese population [19] may be responsible for the difference because DRB5*0101 differs from DRB5*0102 by 3 amino acids in the antigenpeptide binding domain.…”

Section: Discussionmentioning

confidence: 99%

“…The χ 2 test compared the allele frequencies of HLA-DRB1 between the patient groups and a Japanese control population, composed of 491 healthy unrelated individuals selected at random from the general population [19]. The corrected value of P (P c ) was calculated by multiplying P with the number of alleles tested (n=30).…”

Section: Discussionmentioning

confidence: 99%

“…DRB1 alleles of 140 AA patients and 491 healthy Japanese randomly selected from general population [19] were determined using polymerase chain reactions with sequence-specific primers (PCR-SSP) (Micro SSP HLA DNA typing trays; One Lambda, Canoga Park, CA). Genomic DNA was prepared from blood samples using a DNA extraction kit (Generation capture column kit; Gentra, Minneapolis, MN).…”

Section: Determination Of Drb1 Allelesmentioning

confidence: 99%

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Roles of DRB1∗1501 and DRB1∗1502 in the pathogenesis of aplastic anemia

Sugimori

Yamazaki

Feng

et al. 2007

Experimental Hematology

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Category Clinical investigations Word countsTotal text word count: 3412 words Abstract word count: 240 words 2 ABSTRACTObjective. Although a number of reports have documented a significantly increased incidence of HLA-DR15 in aplastic anemia (AA), the exact role of HLA-DR15 in the immune mechanisms of AA remains unclear. We herein clarify the difference between DRB1*1501 and DRB1*1502, the 2 DRB1 alleles which determine the presentation of HLA-DR15, in the pathophysiology of AA. Materials and Methods.We investigated the relationships of the patients' HLA-DRB1 allele with both the presence of a small population of CD55 -CD59 -(PNH-type) blood cells and the response to antithymocyte globulin (ATG) plus cyclosporine (CsA) therapy in 140 Japanese AA patients. Results. Of the 30 different DRB1 alleles, only DRB1*1501 (33.6% vs. 12.8%, P c <0.01) and DRB1*1502 (43.6% vs. 24.4%, P c <0.01) displayed significantly higher frequencies among the AA patients than among a control. AA patients possessing HLA-DR15 tended to be old, and especially, the frequency of DRB1*1502 in patients ≥40 years old (52.4%) was markedly higher than that in those <40 years old (16.2%, P c <0.01). Only DRB1*1501 was significantly associated with the presence of a small population of PNH-type cells and it also showed a good response to ATG plus CsA therapy in a univariate analysis. A multivariate analysis showed only the presence of a small population of PNH-type cells to be a significant factor associated with a good response to the immunosuppressive therapy (P<0.01). Conclusion.Although both DRB1*1501 and DRB1*1502 contribute to the development of AA, the methods of contribution differ between the two alleles.3

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Determination Of Drb1 Allelesmentioning

confidence: 99%

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Roles of DRB1∗1501 and DRB1∗1502 in the pathogenesis of aplastic anemia

Sugimori

Yamazaki

Feng

et al. 2007

Experimental Hematology

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“…In the Japanese population, the DRB1*0405-DQA1*03-DQB1*0401 or DQB1*0302, DRB1*0901-DQA1*03-DQB1*0303, and DRB1*0802-DQA1*03-DQB1*0302 haplotypes are positively associated with type 1 diabetes, whereas the DRB1*1501-DQA1*0102-DQB1*0602 and DRB1*1502-DQA1*0103-DQB1*0601 haplotypes have a negative association (11,12). There is also evidence suggesting that the HLA class I region is another susceptibility locus for type 1 diabetes in humans (13)(14)(15)(16)(17) and mice (18,19).…”

mentioning

confidence: 99%

Combination of HLA-A24, -DQA1*03, and -DR9 Contributes to Acute-Onset and Early Complete β-Cell Destruction in Type 1 Diabetes

Nakanishi

Inoko

2006

Diabetes

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To elucidate the genetic factors contributing to heterogeneity of the rate of ␤-cell destruction in type 1 diabetes, we investigated the relationship between the time course of complete ␤-cell loss and HLA class I and II alleles. HLA allele frequencies were also examined among subgroups classified by the mode of onset. The subjects were 266 type 1 diabetic patients (among whom 196 patients were studied longitudinally) and 136 normal control subjects. Earlier complete loss of ␤-cell function was observed in patients who possessed both HLA-A24 and HLA-DQA1*03 and in patients who had HLA-DR9, compared with those without these HLA alleles (P ‫؍‬ 0.0057 and 0.0093, respectively). Much earlier complete ␤-cell loss was observed in the patients who possessed all of HLA-A24, -DQA1*03, and -DR9 compared with the remaining patients (P ‫؍‬ 0.0011). The combination of HLA-A24, -DQA1*03, and -DR9 showed a higher frequency in acute-onset than slow-onset type 1 diabetes (P ‫؍‬ 0.0002). In contrast, HLA-DR2 was associated with a slower rate of progression to complete ␤-cell loss. These results indicate that the combination of HLA-A24, -DQA1*03, and -DR9 contributes to the acute-onset and early complete ␤-cell destruction, whereas HLA-DR2 has a protective effect against complete ␤-cell loss in type 1 diabetes.

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“…A great deal of progress has been made in identifying statistical associations between HLA and autoimmune diseases (Tiwari and Terasaki 1985;Dong et al 1993;Yasunaga et al 1996;Thorsby 1997). There are at least two possible mechanisms for observed associations.…”

Section: Introductionmentioning

confidence: 99%

An HLA-binding-motif-aided peptide epitope library: A novel library design for the screening of HLA-DR4-restricted antigenic peptides recognized by CD4+T cells

et al. 1998

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Susceptibility to a series of autoimmune diseases is strongly associated with particular HLA class II alleles. Identification of T cell clones and antigenic epitopes bound by HLA class II molecules involved in autoimmune diseases is critical to understanding the etiology of these HLA class II-associated diseases. However, establishment of T cell clones in autoimmune diseases is difficult because the antigenic peptides are unknown. Peptide library methods which include all possible peptide sequences offer a potentially powerful tool for the detection of cross-reactive antigenic peptides recognized by T cells. Here, we reduced the number of peptides per mixture by utilizing the known binding motifs of peptides for the HLA-DRB1*0405 molecule and evaluated the effectiveness of this library design. Each library mixture evoked a strong proliferative response in the unprimed peripheral blood lymphocytes (PBL) from HLA-DRB1*0405-positive donors but little or no response in the PBL from HLA-DRB1*0405-negative donors. The library also detected antigenic peptides that activated three antigen-specific T cell lines restricted by HLA-DRB1*0405, with different specificities. The motif-based approach thus presents a powerful method for monitoring T cells in large, heterogeneous T cell populations and is useful for the identification of the mimic peptide epitopes of T cell lines and clones.

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Different contribution of HLA‐DR and ‐DQ genes in susceptibility and resistance to Insulin‐dependent diabetes mellitus (IDDM)

Cited by 104 publications

References 75 publications

Roles of DRB1∗1501 and DRB1∗1502 in the pathogenesis of aplastic anemia

Roles of DRB1∗1501 and DRB1∗1502 in the pathogenesis of aplastic anemia

Combination of HLA-A24, -DQA1*03, and -DR9 Contributes to Acute-Onset and Early Complete β-Cell Destruction in Type 1 Diabetes

An HLA-binding-motif-aided peptide epitope library: A novel library design for the screening of HLA-DR4-restricted antigenic peptides recognized by CD4+T cells

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