HLA class I/class II interaction in early onset pauciarticular juvenile chronic arthritis

Paul, Christian; Haas, Johannes-Peter; Schoenwald, Ulrich; Truckenbrodt, H; Bettinotti, María P.; Bönisch, Jürgen; Brünnler, Günter; Keller, E.; Nevinny-Stickel, C.; Yao, Zhu; Albert, E. D.

doi:10.1007/bf00171799

Cited by 13 publications

(6 citation statements)

References 17 publications

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“…By contrast, no interaction could be found between DPBI"0201 and DR6 or between HLA-A2 and DR6. In addition, we have found a hierarchy among the various marker combinations, where the risk of developing EOPA-JCA increases with the number of associated markers present in an individual (1,2). Two other groups have also observed HLA interaction: Van Kerckhove and co-workers (3) described HLA-DP/DR interaction and Fernandez-Vina and co-workers (4) HLA class I/class I1 interaction.…”

mentioning

confidence: 65%

Immunogenetics of juvenile chronic arthritis

et al. 1995

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mentioning

confidence: 65%

Immunogenetics of juvenile chronic arthritis

et al. 1995

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“…The complex literature has been drastically curtailed here by refemng only to the major DR-typed haplotypes, irrespective of the DQ alleles with which they are associated (which are in some cases more closely associated with the protective effect). Data are quoted as relative risk, corrected for the presence of susceptibility genes in some (43,44) but not all instances. Applying this correction is recommended, even though its use reflects investigator bias in favor of positive rather than negative associations.…”

Section: Disease Protection Mediated By Hla Allelesmentioning

confidence: 99%

Functional significance of polymorphism among MHC class II gene promoters

et al. 1996

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The functional significance of polymorphism among MHC class II promoters in man and mouse is here reviewed, mainly in terms of the hypothesis of differential expression. The hypothesis proposes that differences between antigen-presenting cells in MHC class II expression exert a co-dominant effect on the Th1-Th2 cytokine balance, such that class II molecules of one type come to control to a greater extent the production of one group of cytokines, and those of another type the production of the alternative group. The survey deals with the influence of signal strength and antigen-presenting cell type on T-cell subset differentiation; functional differences between MHC class II molecules not obviously related to determinant selection; disease protection mediated by HLA alleles; mechanisms possibly responsible for allotypic and isotypic bias; overdominance (heterozygous advantage) in selection for expression of class II alleles; MHC class II promoter structure and function; inter-locus and inter-allele variability within human MHC class II gene upstream regulatory regions; a comparison of these polymorphisms in mouse and man; read-out of class II promoter function; and a comparison with expression of MHC class I. We conclude that the evidence that this variation is functionally active (i.e. controls expression) is increasing, but is not yet compelling. The crucial test still to come, we suggest, is whether or not the biological effects attributable to this polymorphism will line up with molecular studies on expression.

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“…Interestingly, DPB1*0301 has also been associated with RF-negative adult onset RA. 22 While previous studies using different populations have found independent association of HLA-DPB1*0201 [5][6][7][8][9][10][11][12][13] with JIA, we only observed a marginally significant association (P c ¼ 0.05) in non-DRB1*JIASE patients with HLA-DPB1*0201(020102). This may indicate an independent effect of the DPB1*020102 allele in only a particular subset of our pauciarticular patients and/or, less likely, differences in the genetic background of the Finnish population and the other populations previously studied.…”

Section: Discussionmentioning

confidence: 50%

“…[5][6][7][8][9][10][11][12][13] However, only four studies have been published to date of DPB1 examination in polyarticular patients. 6,9,14,15 Although these findings suggest a role of HLA-DPB1 in JIA, the magnitude of an HLA-DPB1 effect and the difference in DPB1 susceptibility between pauciarticular and polyarticular patients remains unclear, particularly in light of the stronger DRB1 associations that have been described.…”

Section: Introductionmentioning

confidence: 99%

HLA-DRB1, TAP2/TAP1, and HLA-DPB1 haplotypes in Finnish juvenile idiopathic arthritis: more complexity within the MHC

Runstadler

Säilä²,

Savolainen³

et al. 2004

Genes Immun

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This study further defines genetic susceptibility to JIA in the region centromeric to HLA-DRB1. DNA from 234 Finnish JIA nuclear families and 639 elderly Finnish control individuals was genotyped for five functional SNPs within the TAP2 and TAP1 loci (B200 kb centromeric of HLA-DRB1). Subsets of the controls (186) and patients (145) that had been previously typed for HLA-DRB1 were also genotyped by sequence for the HLA-DPB1 locus. Case/control and transmission disequilibrium test (TDT) methods revealed an association with the DPB1*030101 allele for JIA (OR 2.3, 95% CI 1.5-3.5). Notably, a detailed haplotypic analysis of the TAP2/TAP1 loci and their interaction with the HLA-DPB1*030101 and DRB1*08 and *11 alleles showed a variety of over-represented and under-represented TAP2/TAP1 haplotypes not evident in the single marker analysis. The strongest effect was observed in the polyarticular RF negative JIA subgroup for the 2-2-1-2-1 TAP2/TAP1 haplotype (TAP2B and TAP1A alleles) which showed an independent effect from both DRB1*08 and *11 (Po0.000003) and DPB1*030101 (P ¼ 0.02). We have provided evidence that the extended haplotypes (including HLA-DRB1, TAP2/TAP1, and HLA-DPB1) of pauciarticular and polyarticular RF negative disease are distinct. This observation may have implications for functional etiological differences between the pauciarticular and polyarticular JIA patients.

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HLA class I/class II interaction in early onset pauciarticular juvenile chronic arthritis

Cited by 13 publications

References 17 publications

Immunogenetics of juvenile chronic arthritis

Immunogenetics of juvenile chronic arthritis

Functional significance of polymorphism among MHC class II gene promoters

HLA-DRB1, TAP2/TAP1, and HLA-DPB1 haplotypes in Finnish juvenile idiopathic arthritis: more complexity within the MHC

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