HLA‐DR4 associated Dw types in rheumatoid arthritis

Ollier, William; Carthy, D.; Cutbush, S.; Okoye, R; Awad, J.; Fielder, A. H. L.; Silman, A J; Festenstein, H.

doi:10.1111/j.1399-0039.1989.tb01674.x

Cited by 31 publications

(17 citation statements)

References 23 publications

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“…This confirmed the previous cellular typing of these 2 extended haplotypes as Dw4 (Ollier et al, 1989) which corresponds toDRBl*O4OI. Also, all patients and controls who carried HLA-A2, B62 and DR4 were DR4 subtyped as having 0401.…”

Section: Hla-dr4 Subtypessupporting

confidence: 78%

“…In view of the increased risk of lymphoid but not myeloid malignancies in RA, it is interesting that CLL, but not CML, shares the same DR4 subtypic association with RA. Given the fact that the commonest ancestral DR4 haplotypes, B44DR4 and B62DR4, both carry DRBl*O401, the DR4 subtypic associations may be simply due to already known haplotypic associations in RA (Ollier et al, 1989;McCluskey et al, 1983;Fraser et aL, 1990) and leukaemia (Dorak et al, 1994~). Furthermore, the haplotype A2B62DR4 is associated with the adult-onset form of RA (Fraser et al, 1990) and the present study showed a strong association of the simultaneous occurrence of its alleles in an adult lymphoid malignancy.…”

Section: Discussionmentioning

confidence: 64%

“…The HLA association with RA has been the subject of extensive studies. These studies identified the common (or extended) haplotypes B44DR4 and B62DR4 (Ollier et al, 1989;McCluskey et al, 1983;Fraser et al, 1990), and among the DR4 subtypes, HLA-DRBI *0401 (Dw4) and 0404 (Dw14) as the major determinants of susceptibility for RA (Winchester, 1994). We have previously shown that the HLA-DR53-associated susceptibility in CML is due to homozygosity for common DR53 haplotypes (Dorak et al, 1994~).…”

Section: Discussionmentioning

confidence: 99%

“…The allelic association with the supertypic specificity HLA-DR53 was further analysed in terms of the DR53 group of haplotypes. Moreover, in view of the similarities in HLA associations between rheumatoid arthritis (RA) and leukaemia (discussed in Dorak et al, 1994b;Dorak and Burnett, 1994), and the relevance of particular subtypes of HLA-DR4 in susceptibility to RA (Ollier et al, 1989;Winchester, 1994); HLA-DR4 subtypes were also examined both in the current series of CLL patients and in the previous group of CML patients. …”

mentioning

confidence: 99%

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Influence of the major histocompatibility complex on age at onset of chronic lymphoid leukaemia

et al. 1996

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The major histocompatibility complex is one of the interactive factors in the multifactorial model of carcinogenesis. Its main influence in experimental models is on the age at onset of malignancies. We have previously shown a similar effect of homozygosity for HLA-DR53 in CML. In the present study, we investigated 79 patients with CLL and 329 local controls from Germany. In addition to full serotyping, all patients and I I 6 of controls were also typed by HU-DR6 PCR analysis. The homozygosity rates for DR53 in patients under and over the median age (60 years) were 18.6% and 2.9%, respectively ( p = 0.03). In experimental models, the major histocompatibility complex (MHC) has an interactive influence on the development of spontaneous, virally or chemically-induced malignancies (Lilly et al., 1964; Boyse et al., 1972;Faraldo et al., 1979;Oomen et al., 1988;Vasmel et al., 1988). Particular alleles of this polymorphic system influence the incidence and phenotype, as well as the age at onset of malignancies (Vasmel et al., 1988;Miyazawa et al., 1992). The interaction of the MHC is not exerted on transformation of a neoplastic clone but occurs during the pre-leukaemic stage (Chesebro, 1981;Lonai et al., 1982). Thus, it does not contain essential susceptibility genes but influences the rate of progression to overt malignancy. More than one MHC gene is involved in the complex, multifactorial development of malignancies (Oomen et al., 1988;Zijlstra and Melief, 1986). Eight of theThe findings in animal models stimulated similar studies investigating the role of the human MHC (HLA complex) in malignancies. The initial serological studies uncovered some associations but did not establish a strong and consistent influence of HLA antigens on the development of neoplasms (Tiwari and Terasaki, 1985). The haemopoietic malignancies have been the most extensively studied ones (Seremetis et al., 1985;Bortin et al., 1987;Caruso et al., 1987;Richter et al., 1973;Nunez-Roldan et al., 1982; Kilpatrick et al., 1984;Dyer et al., 1986;Cuttner et al., 1994). In leukaemia and lymphoma also, no consistent HLA association has been shown by serology.With the advent of molecular typing methods, this issue has been revisited. Recent studies have shown stronger allelic associations, although genotypes, age and gender effect have usually been overlooked (Apple et al., 1994;Klitz et al., 1994). The first DNA-based study investigating the role of the HLA complex in the development of leukaemia showed a strong influence of several independent genotypes on the age at onset of chronic myeloid leukaemia (CML), the strongest one being homozygosity for the supertypic specificity HLA-DR53 (Dorak et al., 1994a). A second molecular study confirmed the role of this homozygous genotype in increased susceptibility to childhood acute lymphoblastic leukaemia (ALL) and also showed a gender effect (Dorak et al., 1995).In the present study, the same association and its influence on the age at onset of chronic lymphoid leukaemia (CLL) were investigated by DNA analy...

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Section: Hla-dr4 Subtypessupporting

confidence: 78%

Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Influence of the major histocompatibility complex on age at onset of chronic lymphoid leukaemia

et al. 1996

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“…In all four studies, no association appeared of any particular HLA-DQ allele with disease, either in adult (9,49,50) or juvenile (51) patients. Thus, the contribution of specifi c HLA-DQ alleles to RA appears to be minimal.…”

Section: Rheumatoid Arthritismentioning

confidence: 71%

MHC Class-II Molecules and Autoimmunity

Nepom

Erlich

1991

Annu. Rev. Immunol.

486

197

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Molecular and genetic studies of HLA class-II genes provide new insights into the basis for MHC associations with autoimmunity. Polymorphisms among class-II genes identify specific haplotypes associated with autoimmune diseases such as type-I diabetes, rheumatoid arthritis, celiac disease, and pemphigus vulgaris. In some cases, single genes within those haplotypes are themselves implicated in disease susceptibility. Interactions, both cis and trans, between candidate susceptibility genes suggest a number of possible mechanisms critical for autoimmune triggering events involving class-II molecules. Amino acid sequence comparisons between products of candidate susceptibility genes and other class-II genes pinpoint a limited number of critical sites within HLA molecules which appear to be responsible for pathogenic events.

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