Editorial: HLA–B27: The Story Continues to Unfold

Powis, Simon J.; Colbert, Robert A.

doi:10.1002/art.39566

Cited by 10 publications

(5 citation statements)

References 18 publications

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“…However, additional hypotheses have emerged in recent years. One model emphasizes the propensity of HLA-B27 to misfold, causing endoplasmic reticulum stress; another emphasizes the recognition of B27 dimers by KIR3DL2 receptors on CD4+ Th17 cells 35 . For the associated DQ alleles, impaired interactions with accessory molecules that regulate peptide loading of HLA class II molecules have been observed and hypothesized to be a basis for presentation of cryptic epitopes of self-proteins, which break immune tolerance 36 .…”

Section: Immunogenetics Of Jpsamentioning

confidence: 99%

Juvenile Psoriatic Arthritis: A Report from the GRAPPA 2017 Annual Meeting

et al. 2018

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Juvenile psoriatic arthritis (JPsA), a subtype of juvenile idiopathic arthritis (JIA), constitutes 5% of JIA. The literature is inconsistent regarding features of JPsA, and physicians debate whether it is a distinct entity within JIA. A biphasic age of onset distribution has been noted. Early-onset disease is characterized by female predominance, small joint involvement, dactylitis, and positive antinuclear antibodies. Late-onset JPsA resembles adult-onset psoriatic arthritis (PsA), with male predominance, psoriasis, enthesitis, and axial disease. Recent studies report improved outcomes, likely due to the widespread use of traditional and biologic disease-modifying antirheumatic drugs. Conflicting HLA associations have been reported in JPsA, but notably both HLA class I and II allele associations are suggested. Similar to PsA cohorts, subjects with JPsA have a lower frequency of a protective interleukin 23R allele than controls or other JIA subtypes. Data in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) patient registry suggest the aggressive characteristics of JPsA: 24.6% of children have joint damage 4.6 years after symptom onset. Pediatric and adult PsA classification criteria define different JPsA cohorts within the registry and support a previous suggestion that the International League of Associations for Rheumatology criteria for JPsA may be overly stringent. Increased collaboration between pediatric and adult physicians and comparative research on these clinically related conditions are warranted.

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Section: Immunogenetics Of Jpsamentioning

confidence: 99%

Juvenile Psoriatic Arthritis: A Report from the GRAPPA 2017 Annual Meeting

et al. 2018

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“…The third hypothesis, the arthritogenic peptide hypothesis, suggests that B27 presents specific peptides, presumably to CD8 ϩ T cells, that induce pathogenic adaptive immune responses. Although this is the most straightforward hypothesis, to date no specific peptide or responding T cell has been convincingly implicated (1,2,6). Moreover, the arthritis and spondylitis that develops spontaneously in HLA-B27 transgenic rats (7) occur even in rats lacking CD8 and CD8 ϩ T cell responses (8).…”

Section: Hla-b27 Is a Class I Major Histocompatibility (Mhc-i) Allelementioning

confidence: 99%

The Human Leukocyte Antigen (HLA)-B27 Peptidome in Vivo, in Spondyloarthritis-susceptible HLA-B27 Transgenic Rats and the Effect of Erap1 Deletion

Barnea

Kadosh

Haimovich

et al. 2017

Molecular & Cellular Proteomics

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HLA-B27 is a class I major histocompatibility (MHC-I) allele that confers susceptibility to the rheumatic disease ankylosing spondylitis (AS) by an unknown mechanism. ERAP1 is an aminopeptidase that trims peptides in the endoplasmic reticulum for binding to MHC-I molecules. ERAP1 shows genetic epistasis with HLA-B27 in conferring susceptibility to AS. Male HLA-B27 transgenic rats develop arthritis and serve as an animal model of AS, whereas female B27 transgenic rats remain healthy. We used large scale quantitative mass spectrometry to identify over 15,000 unique HLA-B27 peptide ligands, isolated after immunoaffinity purification of the B27 molecules from the spleens of HLA-B27 transgenic rats. Heterozygous deletion of Erap1, which reduced the Erap1 level to less than half, had no qualitative or quantitative effects on the B27 peptidome. Homozygous deletion of Erap1 affected approximately one-third of the B27 peptidome but left most of the B27 peptidome unchanged, suggesting the possibility that some of the HLA-B27 immunopeptidome is not processed in the presence of Erap1. Deletion of Erap1 was permissive for the AS-like phenotype, increased mean peptide length and increased the frequency of C-terminal hydrophobic residues and of N-terminal Ala, Ser, or Lys. The presence of Erap1 increased the frequency of C-terminal Lys and Arg, of Glu and Asp at intermediate residues, and of N-terminal Gly. Several peptides of potential interest in AS pathogenesis, previously identified in human cell lines, were isolated. However, rats susceptible to arthritis had B27 peptidomes similar to those of non-susceptible rats, and no peptides were found to be uniquely associated with arthritis. Whether specific B27-bound peptides are required for AS pathogenesis remains to be determined. Data are available via ProteomeXchange with identifier PXD005502.

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“…Существует также гипотеза, согласно которой причиной развития воспалительной реакции у носителей HLA-B*27 являются неправильное свертывание полипептидной цепи белка HLA-B27, клеточная реакция на несвернутый белок в виде стресса эндоплазматического ретикулума и аутофагия [54]. В данном случае патогенетическое значение имеют физико-химические характеристики молекулы белка HLA-B*27 [55]. Медленная сборка комплексов «антигенный пептид-HLA-B27» предрасполагает клетку к повышению уровня ассоциированной с эндоплазматическим ретикулумом деградации накапливающегося несвернутого белка, индукции реакции на несвернутый белок и аутофагии, особенно когда продукция HLA-B27 повышается во время воспаления [54].…”

Section: Discussionunclassified

Genetic markers for psoriatic arthritis among patients with psoriasis. Part II: HLA genes

Kubanov

Чикин

Карамова

et al. 2021

Vestnik dermatologii i venerologii

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Psoriatic arthritis often leads to the development of severe outcomes ankylosis, deformities of the affected joints with severe impairment of their functions and disability. Early identification of patients with psoriasis with an increased risk of developing psoriatic arthritis for the purpose of its timely diagnosis and early initiation of therapy can prevent the development of severe disease outcomes. It is believed that the genes of the HLA system make the greatest individual genetic contribution to the formation of a predisposition to hereditary diseases with polygenic inheritance. The literature review considers the polymorphisms of the genes of the HLA system, associated with the development of psoriatic arthritis, in patients with psoriasis. The HLA alleles that contribute to the development of psoriatic arthritis and its individual forms have been identified. HLA alleles have been identified, which have a protective effect against the development of psoriatic arthritis.

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Editorial: HLA–B27: The Story Continues to Unfold

Cited by 10 publications

References 18 publications

Juvenile Psoriatic Arthritis: A Report from the GRAPPA 2017 Annual Meeting

Juvenile Psoriatic Arthritis: A Report from the GRAPPA 2017 Annual Meeting

The Human Leukocyte Antigen (HLA)-B27 Peptidome in Vivo, in Spondyloarthritis-susceptible HLA-B27 Transgenic Rats and the Effect of Erap1 Deletion

Genetic markers for psoriatic arthritis among patients with psoriasis. Part II: HLA genes

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