Concepts of pathogenesis in psoriatic arthritis: genotype determines clinical phenotype.

Hdl Handle:
http://hdl.handle.net/10147/605652
Title:
Concepts of pathogenesis in psoriatic arthritis: genotype determines clinical phenotype.
Authors:
FitzGerald, Oliver; Haroon, Muhammad; Giles, Jon T; Winchester, Robert
Citation:
Concepts of pathogenesis in psoriatic arthritis: genotype determines clinical phenotype. 2015, 17:115 Arthritis Res. Ther.
Journal:
Arthritis research & therapy
Issue Date:
7-May-2015
URI:
http://hdl.handle.net/10147/605652
DOI:
10.1186/s13075-015-0640-3
PubMed ID:
25948071
Additional Links:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422545/pdf/13075_2015_Article_640.pdf
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.
Item Type:
Article
Language:
en
Keywords:
ARTHRITIS; GENETICS
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
ISSN:
1478-6362

Full metadata record

DC FieldValue Language
dc.contributor.authorFitzGerald, Oliveren
dc.contributor.authorHaroon, Muhammaden
dc.contributor.authorGiles, Jon Ten
dc.contributor.authorWinchester, Roberten
dc.date.accessioned2016-04-18T09:51:38Zen
dc.date.available2016-04-18T09:51:38Zen
dc.date.issued2015-05-07en
dc.identifier.citationConcepts of pathogenesis in psoriatic arthritis: genotype determines clinical phenotype. 2015, 17:115 Arthritis Res. Ther.en
dc.identifier.issn1478-6362en
dc.identifier.pmid25948071en
dc.identifier.doi10.1186/s13075-015-0640-3en
dc.identifier.urihttp://hdl.handle.net/10147/605652en
dc.description.abstractThis 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.en
dc.language.isoenen
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422545/pdf/13075_2015_Article_640.pdfen
dc.rightsArchived with thanks to Arthritis research & therapyen
dc.subjectARTHRITISen
dc.subjectGENETICSen
dc.subject.meshAdulten
dc.subject.meshAllelesen
dc.subject.meshArthritis, Psoriaticen
dc.subject.meshFemaleen
dc.subject.meshGene Expression Regulationen
dc.subject.meshGenetic Predisposition to Diseaseen
dc.subject.meshGenotypeen
dc.subject.meshHLA Antigensen
dc.subject.meshHumansen
dc.subject.meshMaleen
dc.subject.meshMiddle Ageden
dc.subject.meshPhenotypeen
dc.subject.meshPrognosisen
dc.subject.meshSeverity of Illness Indexen
dc.titleConcepts of pathogenesis in psoriatic arthritis: genotype determines clinical phenotype.en
dc.typeArticleen
dc.identifier.journalArthritis research & therapyen
dc.description.fundingOtheren
dc.description.provinceLeinsteren
dc.description.peer-reviewpeer-reviewen

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