HLA‐DR association in rheumatoid arthritis and the shared susceptibility epitope hypothesis

Galeazzi, Mauro; Cappellacci, Sandra; Lulli, Patrizia; Mazzilli, M. C.; Tosi, Roberto; Tanigaki, Nobuyuki

doi:10.1002/anr.1780320525

Cited by 4 publications

(2 citation statements)

References 6 publications

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“…While several cellular subtypes of DR4, like Dw4, Dw14 and Dw15, seem clearly associated with RA (8lo), Dw 10 and Dw13 are not (1 1). Further complexity was created as studies showed that certain epitopes, shared by DR1 and DR4 and defined by monoclonal antibodies (MCI (12), X121.4 (13)) or homozygous typing cell lines (T43 1 (14)), carried an even higher risk for RA.…”

Section: Introductionmentioning

confidence: 99%

HLA‐DR1 and rheumatoid arthntis in Israeli Jews: Sequencing reveals that DRB1*0102 is the predominant HLA‐DR1 subtype

Vries¹,

Rønningen²,

Tilanus³

et al. 1993

Tissue Antigens

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Rheumatoid arthritis (RA) is associated with the HLA-DR4 cellular subtypes Dw4 and Dw14 in Caucasians, with Dw15 in Japanese, and possibly with HLA-DR1 in Israeli Jews. Sequencing studies in Caucasians have shown that these molecules share a common amino acid sequence in the third hypervariable region of the DR molecule (AA 67-74: LLEQRRAA or LLEQKRAA), suggesting that this sequence is primarily associated with RA. An important argument in favor of this shared-epitope hypothesis has been the reported association between DR1 and RA in Israeli Jews. However, a later report did not confirm this association, and cellular typing showed that Israeli DR1 consists of three or more subtypes, suggesting that new subtypes might be present. Since no sequencing data on Israeli HLA-DR1 genes have been reported, we sequenced the first domain (AA 10-91) of the DRB1 gene in 12 DR1-positive Israeli RA patients, 5 healthy controls and a homozygous typing cell (HTC), defining the major Jewish cellular HLA-DR1 subtype. DRB1*0102 (DR1 Dw20) was found in 8 RA patients, 3 controls and the HTC "LVA". DRB1*0101 (DR1 Dw1) was found in 4 RA patients and 2 controls. No other DR1 subtypes were encountered. In all 20 DR1 haplotypes, the DRB1*0101 or 0102 allele was associated with DQA1*0101 and DQB1*0501, being identical to the Caucasian DR1 haplotypes. Thus, at the sequence level, we found no basis for the reported extensive cellular heterogeneity of DR1 in the Israeli population.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Introductionmentioning

confidence: 99%

HLA‐DR1 and rheumatoid arthntis in Israeli Jews: Sequencing reveals that DRB1*0102 is the predominant HLA‐DR1 subtype

Vries¹,

Rønningen²,

Tilanus³

et al. 1993

Tissue Antigens

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“…In fact, a group of DR4' rheumatoid arthritis patients were screened for D P serological specificity WT, along with D R and D Q serological markers that discriminate DR4 haplotypes. Only the D R but not the D Q and DP specificities showed a distribution different from the control group [23], eliminating the possible involvement of the DP subregion in the susceptibility to rheumatoid arthritis.…”

Section: Discussionmentioning

confidence: 59%

Serological detection and molecular localization of allelic HLA‐DP supertypic epitopes

et al. 1989

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A DP serological allospecificity was identified using 125I-labeled preparations of HLA class II molecules isolated from cells of HLA homozygous typing cell lines, SLE (DRw6, DQw1, DPw3) and WT46 (DRw6, DQw1, DPw2), and depleted of DR molecules by absorption with an anti-DR monoclonal antibody. The specificity, provisionally called WT, was carried by class II molecules possessing the characteristics of DP molecules on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and detected primarily in DPw1, DPw3 and DPw5 cells and exceptionally in some DPw2 cells including WT46 and DPw4 cells on a large panel of DP-pretyped B cell lines mostly derived from the 10th International Histocompatibility Workshop B cell reference panel. It was apparently allelic to another DP serological specificity BUT previously defined on DP molecules isolated from cells of DPw2+ HLA deletion mutant cell line LCL 721.82. On the same cell panel; the BUT specificity was negative in all DPw1, DPw3 and DPw5 cells, and positive in all DPw2 and DPw4 cells and also in DPw2B and DPw4B cells except the cells typed WT+. This DP association pattern was similar to that of the known allelic sequences, GGPM and DEAV, in DP beta F segment, one of the six variable segments in the second exon of DP beta gene. Thus, genomic DNA from 22 B cell lines pretyped for BUT and WT specificities were enzymatically amplified for the second exon of DP beta gene by the use of locus-specific oligonucleotide primers and hybridized with 32P-labeled oligonucleotide probes corresponding to the F segment sequence variations. This oligonucleotide typing showed perfect one-to-one correlation with the BUT and WT serological typing. The typing also revealed that WT46 cells, although typed DPw2, have the DEAV sequence common to DPw1, DPw3 and DPw5.

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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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HLA‐DR association in rheumatoid arthritis and the shared susceptibility epitope hypothesis

Cited by 4 publications

References 6 publications

HLA‐DR1 and rheumatoid arthntis in Israeli Jews: Sequencing reveals that DRB1*0102 is the predominant HLA‐DR1 subtype

HLA‐DR1 and rheumatoid arthntis in Israeli Jews: Sequencing reveals that DRB1*0102 is the predominant HLA‐DR1 subtype

Serological detection and molecular localization of allelic HLA‐DP supertypic epitopes

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

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