Dw subtypes of DR4 in rheumatoid arthritis: Evidence for a preferential association with Dw4

Zoschke, David C.; Segall, Miriam

doi:10.1016/0198-8859(86)90322-8

Cited by 50 publications

(20 citation statements)

References 9 publications

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“…So far, cDNA sequence data indicate that these splits are in fact due to differences at the DRP locus (32). In this context, it is interesting that a recent study (33) shows that the frequency of Dw4 is significantly increased in DR4+ RA patients, compared with DR4 + normal individuals. One might suspect that a majority of DR4+ RA patients have class I1 haplotypes that contain both the DRP gene corresponding to Dw4 and the DQP gene corresponding to the B-DQPIV pattern, although this seems not to be the case in healthy controls.…”

Section: Discussionmentioning

confidence: 98%

A dr4‐associated dr‐dq haplotype is significantly associated with rheumatoid arthritis

Wallin

Carlsson

Ströum

et al. 1988

Arthritis & Rheumatism

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Forty-three patients with seropositive, erosive rheumatoid arthritis (RA) and 24 members of 5 RA multicase families were studied for HLA class I1 gene polymorphism, using restriction fragment analysis with complementary DNA probes for DRP and DQP chains. This method generates HLA-DR-DQ haplotypes that are highly correlated with HLA-DR serology. Thirtyfive of the 43 RA patients (81%) were positive for one or for both of the DR4-associated DR-DQ haplotypes, 4.1 and 4.2. Among these patients, the 4.1 haplotype was found significantly more often than in DR4 + controls (P < 0.01). The haplotype segment C3;B15;DR4 was present in all RA patients in 4 of the 5 families, and included the DR-DQ4.1 haplotype.The etiology of rheumatoid arthritis (RA) is still unknown. However, for a long time, a constitutional basis for susceptibility to the disease has been implicated, and this is strongly supported by the finding of Address reprint requests to Johan Wallin, Center for Biotechnology, F82, Huddinge Hospital, S-141 86 Huddinge, Sweden.Submitted for publication November 26, 1986; accepted in revised form May 27, 1987. an association between RA and HLA-Dw4 (1). This specificity is defined using homozygous typing cells. When serologic means of studying class I1 mixed lymphocyte culture (MLC) antigens were introduced, findings clearly indicated that RA was closely associated with HLA-DR4. More recently, additional class 11 loci have been defined using both serologic and cellular typing techniques. Three of these loci contained genes encoding polymorphic products and are now referred to as DP, DQ, and DR.DR antigens have been well characterized using serologic methods, and so far, 12 distinct allelic products have been defined. The DQ locus is closely linked to DR; the DQ alleles exist in strong linkage disequilibrium with particular DR alleles. Serologic typing has only revealed 3 distinct DQ allotypes: wl, w2, and w3. Linkage disequilibrium between DR and DQ is exemplified by the fact that almost all DR4 + individuals are also DQw3 + .New methods have recently been used to study the association between HLA and diseases. Complementary DNA (cDNA) probes have been used to genotype patients for class I1 alleles. A method based on restriction fragment length polymorphism (RFLP) has been developed (2) that, together with recent findings (3), gives a solid basis for the assignment of genetically defined DR-DQ haplotypes, which correlate extremely well with the serologic DR specificities. DRP-specific RFLP gives a resolution similar to that which can be observed when serologic reagents are used. However, genotyping shows a higher degree of polymorphism for the DQ locus than was determined from earlier serologic studies. In 1985, Bohme et a1 (2) defined 7 distinct DQP subtypes. The association between HLA class I1 alleles and insulin-dependent

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Section: Discussionmentioning

confidence: 98%

A dr4‐associated dr‐dq haplotype is significantly associated with rheumatoid arthritis

Wallin

Carlsson

Ströum

et al. 1988

Arthritis & Rheumatism

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“…1 Previous studies showed that there are close correlations between the HLA-DR4-positive genetic background and the occurrence and development of RA. [2][3][4] Additionally, studies on 'molecular mimicry' suggested that EBVgp110 has a common motif with HLA-DR4 and thus can induce and activate autoreactive T cells and cause a series of autoimmune responses and pathologic damage. 5 Although the roles of abnormal T/B cells in RA have been extensively investigated by a large number of researchers, 6-10 a number of papers since the 1990s have revealed that cd T cells with abnormal functions exist in the joints and that these cells characteristically express HLA-DR, suggesting that these cd T cells may play unknown biological roles in RA.…”

Section: Introductionmentioning

confidence: 99%

Antigen-presenting effects of effector memory Vγ9Vδ2 T cells in rheumatoid arthritis

Liu

Miao

et al. 2011

Cell Mol Immunol

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Rheumatoid arthritis is an autoimmune disease that primarily affects the limbs, but the pathogenic mechanism remains unclear. cd T cells, a T-cell subpopulation, are characterized by multiple biological functions and associated with a variety of diseases. This study investigated the antigen-presenting effects of cd T cells and their relationship with rheumatoid arthritis development. We found that Vc9Vd2 T cells (the predominant subtype of cd T cells in peripheral blood) were activated by isopentenyl pyrophosphate to continuously proliferate and differentiate into effector memory cells. The effector memory Vc9Vd2 T cells exhibited phenotypic characteristics of specific antigen-presenting cells, including high HLA-DR and CD80/86 expression. These Vc9Vd2 T cells could present soluble antigens and synthetic peptides to CD41 T cells. Vc9Vd2 T cells with different phenotypes showed different cytokine secretion patterns. Effector memory Vc9Vd2 T cells simultaneously secreted not only interferon (IFN)-c but also IL-17. The peripheral blood and joint synovial fluid from RA patients contained numerous heterogeneous cd T cells that were predominantly effector memory Vc9Vd2 T cells with the ability to secrete inflammatory factors. We also found that cd T cells had a similar antigen-presenting capability to B cells. These results suggest that during the development of rheumatoid arthritis, cd T cells can aggravate immune dysfunction and produce abnormal immune damage by secreting cytokines and inducing inflammatory cells to participate in synergistic inflammatory responses. Furthermore, cd T cells can behave similarly to B cells to present viral peptides and autoantigen peptides to CD4 1 T cells, thus sustaining CD4 1 T-cell activation.

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“…These include Dw4, DwlO, Dw13, Dw14, and Dw1.5 (or DRB1*0401-0405). Among the D R 4 subtypes, Dw4 (19,20), Dw14 (21), and Dw15 (22) have been associated with enhanced susceptibility to the development of RA; howevcr, the DwlO subtype is not associated with the disease. The terminology is sometimes misleading, and it should be emphasized that DwlO and DRwlO refer to entirely distinct alleles.…”

Section: Class I1 Major Histocompatibility Complex Gene Sequences In mentioning

confidence: 99%

“…RNA was isolated from 10' Epstein-Barr virus-transformed B lymphocytes from patient 2 (29). cDNA was synthesized from 10 pg of total cellular RNA and sub.jected to 20 cycles of Tuq 1 DNA polymerase amplification with oligonucleotide primers (5'-ACA GTG ACA CTG ATG GTG CT-3' and 5'-CAG ACC AGG AGG TTG TGG TG-3') flanking the first domain of the DRP gene (30). A 400-nucleotide DNA band was purified and ligated into the Bluescript MI3 vector (Bethesda Research Laboratories, Gaithersburg, MD), using the Sst 1 site in the 5' end and a blunt-end ligation into the Smu 1 restriction endonuclease site at the 3' end.…”

Section: Construction Of the Complementary Dna (Cdna) Library And Chamentioning

confidence: 99%

Class ii major histocompatibility complex gene sequences in rheumatoid arthritis. The third diversity regions of both DRβ₁ genes in two DR1, DRw10–positive individuals specify the same inferred amino acid sequence as the DRβ₁ and DRβ₂ Genes of a DR4 (Dw14) haplotype

Merryman¹,

Crapper²,

Lee³

et al. 1989

Arthritis & Rheumatism

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The DRl and DRwlOP, chain genes were isolated from each of 2 individuals with rheumatoid arthritis who were heterozygous for these class I1 major histocompatibility complex specificities. The sequences of the DRIP, chains from both patients were identical, differing from previously reported DRP, chains of individuals without RA by 2 amino acid substitutions, at positions 85 (Val-Ala) and 86 (Gly-Val), and by a silent mutation at the last nucleotide of codon 78 (C-T), resulting in the loss of a Pst I restriction endonuclease site. Identical DRwlOP, chain genes were found in both patients. These were shown to encode the epitope recognized by monoclonal antibody 109d6. This antibody also recognizes an epitope on the DRw53P, chain of the DR4 haplotype. The third diversity regions of the DRIP (amino acids 67-74) and the DRwlOP, chains (amino acids 67-73) were identical, respectively, with those of the DR4 (Dw14) PI and P2 chains, raising the possibility that in these patients, the third diversity regions of the two DRP, chain genes present in trans are conformationally equivalent to the cis-encoded third diversity regions of the DR4 (Dw24), DRP,, and Pz chains. The nucleotide sequences of the DQP complementary DNA clones were identical to that of the DQwlP chain, and no DRP, complementary DNA clones were identified.

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Dw subtypes of DR4 in rheumatoid arthritis: Evidence for a preferential association with Dw4

Cited by 50 publications

References 9 publications

A dr4‐associated dr‐dq haplotype is significantly associated with rheumatoid arthritis

A dr4‐associated dr‐dq haplotype is significantly associated with rheumatoid arthritis

Antigen-presenting effects of effector memory Vγ9Vδ2 T cells in rheumatoid arthritis

Class ii major histocompatibility complex gene sequences in rheumatoid arthritis. The third diversity regions of both DRβ₁ genes in two DR1, DRw10–positive individuals specify the same inferred amino acid sequence as the DRβ₁ and DRβ₂ Genes of a DR4 (Dw14) haplotype

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Dw subtypes of DR4 in rheumatoid arthritis: Evidence for a preferential association with Dw4

Cited by 50 publications

References 9 publications

A dr4‐associated dr‐dq haplotype is significantly associated with rheumatoid arthritis

A dr4‐associated dr‐dq haplotype is significantly associated with rheumatoid arthritis

Antigen-presenting effects of effector memory Vγ9Vδ2 T cells in rheumatoid arthritis

Class ii major histocompatibility complex gene sequences in rheumatoid arthritis. The third diversity regions of both DRβ1 genes in two DR1, DRw10–positive individuals specify the same inferred amino acid sequence as the DRβ1 and DRβ2 Genes of a DR4 (Dw14) haplotype

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Class ii major histocompatibility complex gene sequences in rheumatoid arthritis. The third diversity regions of both DRβ₁ genes in two DR1, DRw10–positive individuals specify the same inferred amino acid sequence as the DRβ₁ and DRβ₂ Genes of a DR4 (Dw14) haplotype