HLA‐DRB1*01 and DRB1*04 alleles in Sardinian rheumatoid arthritis patients

Carcassi, Carlo; Passiu, Giuseppe; Lai, Sara; Sanna, Giuseppina; Cauli, Alberto; Alba, F.; Mathieu, Alessandro; Contu, L.

doi:10.1034/j.1399-0039.1999.530110.x

Cited by 3 publications

(4 citation statements)

References 27 publications

(25 reference statements)

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“…SE genotypes that are most commonly suggested to be of general importance to RA severity include those of the DRB1*0401/*0404 compound heterozygote (23,26) and the DRB1*0401 homozygote (54). However, it is noteworthy that both ethnicity (55,56) and sex (57,58) may influence the association of RA with particular SE alleles.…”

Section: Discussionmentioning

confidence: 92%

Impact of shared epitope genotype and ethnicity on erosive disease: A meta‐analysis of 3,240 rheumatoid arthritis patients

Gorman¹,

Lum²,

Chen³

et al. 2004

Arthritis & Rheumatism

130

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Objective. The strongest known genetic association in rheumatoid arthritis (RA) is with HLA-DRB1 alleles that share a similar amino acid sequence, termed the shared epitope (SE). Although many studies have examined the association of the SE with disease severity, the results have been inconsistent, which may reflect the relatively small sample sizes or ethnic differences. The aim of this study was to assess the association of HLA-DRB1 SE alleles and genotype with the development of bony erosions in RA by meta-analysis.Methods. We identified English-language articles published between January 1, 1987 and June 1, 1999 through Medline, EMBase, and manual searches of 6 relevant journals. Included were studies in which molecular typing of HLA-DRB1 alleles was performed and in which the presence or absence of bony erosions was reported. Data were extracted from the studies, and erosions were coded as present or absent. Authors were contacted for missing information and data on individual patients.Results. A total of 29 studies and 3,240 patients were available for analysis. The summary odds ratios Conclusion. The SE is associated with the

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Section: Discussionmentioning

confidence: 92%

Impact of shared epitope genotype and ethnicity on erosive disease: A meta‐analysis of 3,240 rheumatoid arthritis patients

Gorman¹,

Lum²,

Chen³

et al. 2004

Arthritis & Rheumatism

130

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“…HLA-DRB1 * 01:01 (47.2%) followed by DRB1 * 03:01 (41.7%) and DRB1 * 04:01 (41.6%) worldwide (Figure 3A ). Notably, people with greater frequency of DRB1 * 01:01, DRB1 * 04:01 and DRB1 * 04:04 are at higher relative risk of microbial pathogenesis and autoimmune diseases like rheumatoid arthritis (Carcassi et al, 1999 ; Kapitany et al, 2005 ), haemolytic transfusion reactions (Reviron et al, 2005 ), psoriasis vulgaris (Cardoso et al, 2005 ), recurrent respiratory papillomatosis (Bonagura et al, 2004 ), and rheumatoid vasculitis (Gorman et al, 2004 ). We could not observe noticeable binding with the other tested alleles (Figures 3A–C ).…”

Section: Resultsmentioning

confidence: 99%

“…Eighteen of such peptides not only exhibited promiscuous binding, but some of them showed high affinity for HLA class II alleles. DRB1 * 01:01, DRB1 * 04:01 and DRB1 * 04:04 HLA alleles are known to be associated with rheumatoid arthritis, haemolytic transfusion reactions, psoriasis vulgaris, recurrent respiratory papillomatosis and rheumatoid vasculitis autoimmune diseases (Carcassi et al, 1999 ; Bonagura et al, 2004 ; Gorman et al, 2004 ; Cardoso et al, 2005 ; Kapitany et al, 2005 ; Reviron et al, 2005 ). Previous studies indicate that polypeptides like Cop 1, glatiramer acetate, Copaxone can suppress the autoreactive T cells and subsequently inhibit the development of autoimmune diseases (Sela, 2006 ).…”

Section: Discussionmentioning

confidence: 99%

Morbid Sequences Suggest Molecular Mimicry between Microbial Peptides and Self-Antigens: A Possibility of Inciting Autoimmunity

et al. 2017

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Understanding etiology of autoimmune diseases has been a great challenge for designing drugs and vaccines. The pathophysiology of many autoimmune diseases may be attributed to molecular mimicry provoked by microbes. Molecular mimicry hypothesizes that a sequence homology between foreign and self-peptides leads to cross-activation of autoreactive T cells. Different microbial proteins are implicated in various autoimmune diseases, including multiple sclerosis, human type 1 diabetes, primary biliary cirrhosis and rheumatoid arthritis. It may be imperative to identify the microbial epitopes that initiate the activation of autoreactive T cells. Consequently, in the present study, we employed immunoinformatics tools to delineate homologous antigenic regions between microbes and human proteins at not only the sequence level but at the structural level too. Interestingly, many cross-reactive MHC class II binding epitopes were detected from an array of microbes. Further, these peptides possess a potential to skew immune response toward Th1-like patterns. The present study divulges many microbial target proteins, their putative MHC-binding epitopes, and predicted structures to establish the fact that both sequence and structure are two important aspects for understanding the relationship between molecular mimicry and autoimmune diseases. Such findings may enable us in designing potential immunotherapies to tolerize autoreactive T cells.

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“…For example, ORB I *040 I and *0404, carrying QKRAA and QRRAA motifs respectively, predominate in Northern Europe (24); ORBI *0405 and *1001 are the most frequent in Asiatics (25)(26), *1001 being also present in Spain; ORB 1*010 I, together with ORB 1*040 I, *0404-05 share the epitope Q(K/R)RAA which is associated with RA in Mediterranean patients, including Italians (12,(27)(28)(29); ORBI*1402, 0802, 0811 and 0407, on the other hand, absent or poorly represented in the Italian population, have a significantly higher gene frequency among Native Americans than other ORB I alleles (Navajo and Pimans of Gila River Indian Community of Arizona, Lakota Sioux, Seri tribe of Northwest Mexico) (30)(31)(32). Lastly, among RA patients from some Amerindian racial groups having ORI4 as the most common DR antigen, neither HLA-ORI nor OR4 was found to be associated with specific features of RA or severity of the disease (30, 33L…”

Section: Discussionmentioning

confidence: 99%

Genetic Predisposition to Rheumatoid Arthritis in a Tuscan (Italy) Ancient Human Remain

Fontecchio

Ma²,

Azzarone³

et al. 2007

Int J Immunopathol Pharmacol

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Rheumatoid arthritis (RA) is currently believed to have originated in America, and after the discovery of this continent in 1492, to have been exported to the Old World. We evaluated the genetic predisposition to RA in the “Braids Lady” from Arezzo (Italy), a partially mummified woman's body dating back to the end of 1500 AD which presents the anatomical and pathological features of this disease. The study of the polymorphic HLA-DRB1 locus, which includes alleles strongly associated with RA onset, has received much attention over recent years, especially the loci codifying for the DR1 and DR4 antigens, widely represented in the Mediterranean population, and for DR14, widespread among Native Americans. Molecular analysis was performed on extracts of DNA from the mummy, firstly from histological bone sections and then from the whole bone. Two different HLA typing techniques, PCR-sequence-specific oligonucleotides (PCR-SSO) and PCR-sequence-specific primers (PCR-SSP), were employed to identify HLA-DRB alleles. Both genotyping methods showed that the “Braids Lady” carried the DRB1*0101 allele, the serological equivalent of the DR1 antigen. Although the possession of RA risk factor genes cannot be considered a diagnostic marker, the positive result of the Italian mummy for DRB1*0101 and the RA features present, support the idea that this pathology was present in the Old World from at least the mid-16th century. A pathogenetic hypothesis of RA which might well explain its worldwide diffusion is the “molecular mimicry”, resulting from a cross-reactive antibody response between certain microbial antigens and shared epitopes of specific HLA-DR1, DR4 and DR14 susceptibility alleles, the frequency of which varies among different ethnic groups.

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HLA‐DRB101 and DRB104 alleles in Sardinian rheumatoid arthritis patients

Cited by 3 publications

References 27 publications

Impact of shared epitope genotype and ethnicity on erosive disease: A meta‐analysis of 3,240 rheumatoid arthritis patients

Impact of shared epitope genotype and ethnicity on erosive disease: A meta‐analysis of 3,240 rheumatoid arthritis patients

Morbid Sequences Suggest Molecular Mimicry between Microbial Peptides and Self-Antigens: A Possibility of Inciting Autoimmunity

Genetic Predisposition to Rheumatoid Arthritis in a Tuscan (Italy) Ancient Human Remain

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