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Concepts of pathogenesis in psoriatic arthritis: genotype determines clinical phenotype.
FitzGerald, Oliver Haroon, Muhammad Giles, Jon T Winchester, Robert
FitzGerald, Oliver
Haroon, Muhammad
Giles, Jon T
Winchester, Robert
Advisors
Editors
Other Contributors
Departments
Date
2015-05-07
Date Submitted
Keywords
ARTHRITIS
GENETICS
GENETICS
Other Subjects
Subject Mesh
Adult
Alleles
Arthritis, Psoriatic
Female
Gene Expression Regulation
Genetic Predisposition to Disease
Genotype
HLA Antigens
Humans
Male
Middle Aged
Phenotype
Prognosis
Severity of Illness Index
Alleles
Arthritis, Psoriatic
Female
Gene Expression Regulation
Genetic Predisposition to Disease
Genotype
HLA Antigens
Humans
Male
Middle Aged
Phenotype
Prognosis
Severity of Illness Index
Planned Date
Start Date
Collaborators
Principal Investigators
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OA Article
Adobe PDF, 826.05 KB
Alternative Titles
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Abstract
This review focuses on the genetic features of psoriatic arthritis (PsA) and their relationship to phenotypic heterogeneity in the disease, and addresses three questions: what do the recent studies on human leukocyte antigen (HLA) tell us about the genetic relationship between cutaneous psoriasis (PsO) and PsA - that is, is PsO a unitary phenotype; is PsA a genetically heterogeneous or homogeneous entity; and do the genetic factors implicated in determining susceptibility to PsA predict clinical phenotype? We first discuss the results from comparing the HLA typing of two PsO cohorts: one cohort providing the dermatologic perspective, consisting of patients with PsO without evidence of arthritic disease; and the second cohort providing the rheumatologic perspective, consisting of patients with PsA. We show that these two cohorts differ considerably in their predominant HLA alleles, indicating the heterogeneity of the overall PsO phenotype. Moreover, the genotype of patients in the PsA cohort was shown to be heterogeneous with significant elevations in the frequency of haplotypes containing HLA-B*08, HLA-C*06:02, HLA-B*27, HLA-B*38 and HLA-B*39. Because different genetic susceptibility genes imply different disease mechanisms, and possibly different clinical courses and therapeutic responses, we then review the evidence for a phenotypic difference among patients with PsA who have inherited different HLA alleles. We provide evidence that different alleles and, more importantly, different haplotypes implicated in determining PsA susceptibility are associated with different phenotypic characteristics that appear to be subphenotypes. The implication of these findings for the overall pathophysiologic mechanisms involved in PsA is discussed with specific reference to their bearing on the discussion of whether PsA is conceptualised as an autoimmune process or one that is based on entheseal responses.
Language
en
ISSN
1478-6362
eISSN
ISBN
DOI
10.1186/s13075-015-0640-3
PMID
25948071