Rheumatoid Arthritis

Christiansen, F.; Kelly, Heath; Dawkins, R. L.

doi:10.1007/978-3-642-69770-8_123

Cited by 15 publications

(16 citation statements)

References 12 publications

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“…This is in accordance with previous findings recorded by Nepom et al [26] and Christiansen et al [36]. If, however, only the DR4-patients are taken into consideration, the DR1 frequency is significantly increased.…”

Section: Discussionsupporting

confidence: 93%

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HLA-DR1 and DRw6 association in DR4-negative rheumatoid arthritis patients

Läng

Melchers

Urlacher³

et al. 1990

Rheumatol Int

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This study of 110 seropositive rheumatoid arthritis (RA) patients confirms the significant association of susceptibility to RA with HLA-DR4 specificity (P less than 0.001). The DR1 frequency is elevated in the entire seropositive patient group, reaching marginal significance (P less than 0.025). The DR4-negative patients, however, have a much higher prevalence of DR1 (P less than 0.001). Surprisingly, the DRw6 specificity is significantly increased in the remaining DR4- and DR1-negative patients (P less than 0.01). These results demonstrate that RA is not associated with a single HLA-specificity, but to various degrees with DR4, DR1, and DRw6. These findings, and particularly the newly recognized association with DRw6, support the hypothesis that functionally equivalent shared epitopes or conformations on otherwise distinct MHC molecules may confer risk for developing RA.

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Section: Discussionsupporting

confidence: 93%

“…The DR1 frequency is particularly high in individuals from Mediterranean countries [31 35]. In some studies on North American Caucasoids, the DR4-group displayed a significantly elevated frequency of the DR1 haplotype [26,36].…”

Section: Discussionmentioning

confidence: 99%

HLA-DR1 and DRw6 association in DR4-negative rheumatoid arthritis patients

Läng

Melchers

Urlacher³

et al. 1990

Rheumatol Int

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“…Nepom et al (14) found that DR4/Dw14 is significantly associated with RA in Caucasians . Several reports have described the significant association of DRl with RA (15,16). Furthermore, Duquesnoy et al (17) reported that MCI, which is a supertypic specificity associated with DR1 and a part of DR4, is more strongly associated with RA than DR4.…”

Section: Resultsmentioning

confidence: 99%

Putative amino acid sequence of HLA-DRB chain contributing to rheumatoid arthritis susceptibility.

Watanabe

Tokunaga

Matsuki

et al. 1989

The Journal of Experimental Medicine

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The association between HLA-DR4 and rheumatoid arthritis (RA) has been established in many ethnic groups. To clarify the determinant of susceptibility to RA, a polymorphic segment of the HLA-DRB gene was amplified in vitro by polymerase chain reaction and analyzed with oligonucleotide probes specific for the HLA-DR4 DNA sequences. A particular sequence encoding amino acids Gln70-Arg71-Arg72-Ala73-Ala74 showed a strong association with RA (p less than 0.005, relative risk 6.0). This amino acid sequence occurs in the DRB molecules with three RA-associated specificities, DR4/Dw14, DR4/Dw15, and DR1. DR4/Dw4, which is common in Caucasian RA patients, has a strikingly similar amino acid sequence Gln70-Lys71-Arg72-Ala73-Ala74 in terms of polarity and charge profiles. Other RA nonassociated sequences differ from this sequence by at least one amino acid substitution that causes the change of the net charge. The composition of amino acid residues at the positions 70-74 may play a crucial role in the pathogenesis of RA.

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“…The association of Rheumatoid Arthritis (RA) with HLA-DR4 or -Dw4 is well established among several populations (Stastny 1977, 1978, 1980, Mehra et al 1982. Family studies, however, have thus far failed to show unequivocally an HLA-linked susceptibility gene (Khan 1982, Stastny et al 1983, Christiansen et al 1984. This descrepancy may be due to several factors such as disease heterogeneity (Stastny et al 1983, Young et al 1984, de Jongh et al 1984, multifactorial etiology of the disease (Khan et al 1983), ascertainment bias of multicase families and methodological problems with linkage studies of HLA-associated diseases.…”

mentioning

confidence: 99%

“…These 3 families were * ** only siblings older than the youngest age of onset of affected children were analysed. also included in the 9th Histocompatibility Workshop study on familial RA (Christiansen et al 1984).…”

mentioning

confidence: 99%

Paradoxical inheritance of HLA‐Iinked susceptibility to rheumatoid arthritis

et al. 1985

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In order to clarify the discrepancy between population studies showing association of rheumatoid arthritis (RA) with HLA‐DR4/‐Dw4 and family studies failing to show linkage with HLA, we analysed 16 multicase families in which RA and DR4 status of both parents was known. 120 HLA‐haplotypes of affected and unaffected children could be analysed for co‐segregation with RA. In a combined analysis of both affected and unaffected children co‐segregation of RA with the DR4 carrying haplotype was observed when both parents were unaffected (p=0.001). Co‐segregation of RA with one of the two haplotypes of affected parents was observed (p=0.01), but in this case there was no preference for the DR4 carrying haplotype. In both cases preferential inheritance of the other (not associated with RA) haplotype was observed in unaffected siblings. These data indicate that susceptibility to RA is controlled by an HLA‐linked gene. This gene is often but not always identical to the gene coding for a product carrying the DR4 epitope or in strong linkage disequilibrium with it. Combined with previous population data, the present data provide evidence for genetic heterogeneity of RA. Finally, they contain a paradox, based on which a new hypothesis for HLA‐linked susceptibility to RA is formulated.

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Rheumatoid Arthritis

Cited by 15 publications

References 12 publications

HLA-DR1 and DRw6 association in DR4-negative rheumatoid arthritis patients

HLA-DR1 and DRw6 association in DR4-negative rheumatoid arthritis patients

Putative amino acid sequence of HLA-DRB chain contributing to rheumatoid arthritis susceptibility.

Paradoxical inheritance of HLA‐Iinked susceptibility to rheumatoid arthritis

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