DR antigens and rheumatoid arthritis: a study of two populations.

Woodrow, J. C.; Nichol, F. E.; Zaphiropoulos, G

doi:10.1136/bmj.283.6302.1287

Cited by 120 publications

(37 citation statements)

References 7 publications

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“…As discussed, in some studies DRI has been associated weakly with a risk of RA (10)(11)(12)(13)(14). Are epitopes found in common between DR4 subtypes and DRl alleles?…”

Section: Risk For Pemphigus Vulgaris May Be Due To a Third Hypervariamentioning

confidence: 99%

The shared epitope hypothesis. an approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis

Gregersen

Silver

Winchester

1987

Arthritis & Rheumatism

2,289

1,346

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Understanding the inheritance of rheumatoid arthritis (RA) has been the quest of intense investigation over the last decade. One major focus of these efforts has been the attempt to identify genes within the class I1 region of the major histocompatibility complex (MHC) that confer susceptibility for disease. These studies have been based largely on finding associations between class I1 serologic specificities and disease. The results have not been simple to interpret, and lucid analysis is made more difficult by the highly complicated nomenclature that is used to describe the class I1 HLA system. The advent of recombinant DNA technology, however, has greatly expanded our knowledge of this system over the last few years and has offered alternative interpretations of disease association data. One such interpretation, the shared epitope hypothesis, has been described previously (1) and is the subject of this review.To understand the shared epitope hypothesis, one must have some knowledge of the genetic organization of the class I1 region and of the biochemical structure of class I1 molecules. Briefly, the human class I1 region (Figure 1) extends to nearly l , OOO, OOO base pairs, and includes at least 14 different genes. With the exception of DOp and DZa, these genes are generally found in 1 of 3 major subregions: DR, DQ, or DP.Each subregion contains at least 1 functional a Figure 2. Alpha and beta chains from the DQ subregion are polymorphic (i.e., there are multiple alleles at each locus in the population), and together they encode the DQ serologic specificities (DQwl-3).The DR subregion also contains 2 functional p chain genes, designated DRPI and DRPIII. These p chains are both polymorphic. The D W I gene encodes the classic DR specificities (DR1-14); the DRPIII gene encodes the DRw52 and DRw53 specificities. The genes within the DR and DQ subregions are very closely linked and are almost always inherited together as a unit. Therefore, DR and DQ subregion alleles form stable haplotypes in the population. For example, the DR4 allele (encoded by the D W I gene) is almost always found in association with DRw53 (encoded by DRpIII) and DQw3 (encoded by DQ a and P), thus forming the typical DR4,DRw53,DQw3 haplotype. As discussed herein, all the variability between different DR4 haplotypes is located in the DRPI gene. The other linked genes, namely DRPIII, DQa, and DQP, are identical in all DR4 haplotypes, with few exceptions (2,3).The structural features of class I1 molecules at the cell surface are shown in Figure 2 (top). For comparison, class I molecules are also shown. In the case of class I1 molecules, both a and P chain molecules are inserted into the membrane and associate with each other in a noncovalent fashion to form an alp heterodimer. The class I1 p chain contains 2 immunoglobulin-like external domains. The first, or N-terminal, domain (Figure 2) is the site of most of thevariability

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“…As discussed, in some studies DRI has been associated weakly with a risk of RA (10)(11)(12)(13)(14). Are epitopes found in common between DR4 subtypes and DRl alleles?…”

Section: Risk For Pemphigus Vulgaris May Be Due To a Third Hypervariamentioning

confidence: 99%

The shared epitope hypothesis. an approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis

Gregersen

Silver

Winchester

1987

Arthritis & Rheumatism

2,289

1,346

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“…Studies have shown a strong association between the disease and HLA-DR antigens in different ethnic groups: DR4 in Caucasian, American black, and Japanese patients with RA, DRl in Asian Indian and Ashkenazi Jewish patients, and Dw16 in Yakima Indians (1)(2)(3). The association is not complete, and 2630% of Caucasian patients do not carry DR4.…”

mentioning

confidence: 99%

Linkage Between Rheumatoid Arthritis Susceptibility and the Presence of HLA—DR4 and DRβ Allelic ThIrd Hypervariable Region Sequences in Southern Chinese Persons

Li²,

Cohen³

et al. 1992

Arthritis & Rheumatism

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“…Rheumatoid factors are autoantibodies that are directed against the Fc fragment of IgG. Cellular immunity is also thought to be important because of the linkage of RA to certain MHC-encoded T cell restriction elements (e.g., DR4 and DR1 [3,4]). Examination of RA synovial tissue shows high levels of proinflammatory cytokines IL-1 (5), TNF-␣ (6-8), and growth factors such as GM-CSF (7) and M-CSF (8), but the T cell-derived mediators IL-2 (8), , , and TNF-␤ (10) are either absent or present at low levels.…”

Section: Introductionmentioning

confidence: 99%

Polyclonal antibody directed against human RANTES ameliorates disease in the Lewis rat adjuvant-induced arthritis model.

Barnes¹,

Tse²,

Kaufhold³

et al. 1998

J. Clin. Invest.

169

124

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DR antigens and rheumatoid arthritis: a study of two populations.

Cited by 120 publications

References 7 publications

The shared epitope hypothesis. an approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis

The shared epitope hypothesis. an approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis

Linkage Between Rheumatoid Arthritis Susceptibility and the Presence of HLA—DR4 and DRβ Allelic ThIrd Hypervariable Region Sequences in Southern Chinese Persons

Polyclonal antibody directed against human RANTES ameliorates disease in the Lewis rat adjuvant-induced arthritis model.

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