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A Clinical and Genetic Study of Psoriatic Arthritis
Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Reumatology.
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Psoriatic arthritis (PsA) is an inflammatory joint disease associated with psoriasis. PsA has a heterogeneous pattern, expressed by different manifestations such as mild mono-oligoarthritis or very severe, erosive and destructive polyarthritis. Measurable inflammatory activity is not always prominent. The aetiology is unknown but genetic factors are believed to be of importance. The pattern of inheritance is proposed to be polygenic. The aim of this study was to estimate the prevalence of joint and axial manifestations, characterise the disease in relation to inflammatory and genetic markers, and to identify disease susceptibility gene(s) for PsA in patients from northern Sweden.

All patients from the city of Umeå (n=276), selected from a community and hospital based psoriasis register (n=1737) at the Dept of Dermatology, were invited to a prevalence study. Two hundred-two patients were examined and 97 (48%) had inflammatory manifestations such as peripheral arthritis, axial disease, undifferentiated spondylarthropathy (uSpA) and enthesopathies. Of the 67 patients (33 %) with peripheral arthritis and/or axial disease, 30 were not previously diagnosed.

The association of clinical manifestations and potential markers of aggressive joint disease with HLA associations were analysed in 88 patients with PsA. We were not able to confirm findings of other groups reporting strong association with several HLA-antigens. The prevalence of HLA-B17, B37 and B62 was increased compared with controls, but the strongest predictive factors among our patients for an aggressive disease, in a multiple logistic analysis, were polyarthritic disease and distal interphalangeal engagement.

In order to investigate for disease susceptibility genes, five genetic loci were analysed with microsatellites and single nucleotide polymorphisms in an association study of 120 patients with PsA. There was a significant association with the TNFB locus on chromosome 6p but not with any other loci examined; 1q21 (PSORS4), 3q21 (PSORS5), 8q24 and CTLA4. When stratifying for the TNFB alleles the association was confined to allele 123. In a subgroup of patients who were HLA-typed (n=83), we were not able to verify linkage disequilibrium with the TNFB allele 123 and the HLA antigens; B17, B27, B37, B62 or Cw*0602.

The presence of renal abnormalities was evaluated as a manifestation of systemic inflammation in 73 patients with PsA. Renal abnormalities defined as decreased creatinine-clearance (≤ mean - 2SD) and/or urinary albumin >25 mg/24 h was found in 23% of the patients. The predictive factors for renal abnormalities was inflammatory activity (ESR > 25 mm/h and/or CRP >15 mg/L) indicating a systemic effect in some of the patients.

In conclusion, we found high prevalence of inflammatory manifestations in patients with psoriasis. There was no strong association between PsA and HLA antigens and predictive factors for aggressive disease were polyarthritic disease and DIP joint engagement. The TNFB locus was associated with PsA and there were no linkage disequilibrium with the HLA antigens B17, B27, B62 or Cw*0602. There were evidence for systemic effects as renal abnormalities in patients with PsA and measurable inflammatory activity.

Place, publisher, year, edition, pages
Umeå: Folkhälsa och klinisk medicin , 2003. , 67 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 829
Keyword [en]
Public health, Psoriatic arthritis, prevalence, inflammatory manifestations, genetic loci, HLA, TNFB
Keyword [sv]
Folkhälsomedicin
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Research subject
Clinical Genetics
Identifiers
URN: urn:nbn:se:umu:diva-78ISBN: 91-7305-398-8 (print)OAI: oai:DiVA.org:umu-78DiVA: diva2:144500
Public defence
2003-03-28, Umeå, 09:00 (English)
Available from: 2003-03-28 Created: 2003-03-28 Last updated: 2009-10-16Bibliographically approved
List of papers
1. Inflammatory joint manifestations are prevalent in psoriasis: prevalence study of joint and axial involvement in psoriatic patients, and evaluation of a psoriatic and arthritic questionnaire
Open this publication in new window or tab >>Inflammatory joint manifestations are prevalent in psoriasis: prevalence study of joint and axial involvement in psoriatic patients, and evaluation of a psoriatic and arthritic questionnaire
2002 (English)In: Journal of Rheumatology, Vol. 29, no 12, 2577-82 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:umu:diva-5108 (URN)
Available from: 2003-03-28 Created: 2003-03-28 Last updated: 2011-01-18Bibliographically approved
2. Disease manifestations and HLA antigens in psoriatic arthritis in northern Sweden
Open this publication in new window or tab >>Disease manifestations and HLA antigens in psoriatic arthritis in northern Sweden
2002 (English)In: Clinical Rheumatology, ISSN 0770-3198, E-ISSN 1434-9949, Vol. 21, no 5, 357-362 p.Article in journal (Refereed) Published
Abstract [en]

The aim of this study was to identify potential markers of aggressive joint manifestations and HLA associations in patients with psoriatic arthritis (PsA) in northern Sweden. Patients with PsA were examined clinically, with laboratory tests and radiologically. The classification of the disease was based on peripheral and/or axial engagement. HLA B17, B37 and B62 were significantly increased in PsA patients. Univariate analyses suggest that the HLA antigens B37, B62 and some clinical variables were associated with disease course. However, in multivariate analyses distal interphalangeal joint affliction and polyarticular manifestations were the only variables remaining significantly associated with irreversible joint destruction or deformity. There were no significant effects of HLA antigens. In this cross-sectional study, clinical manifestations were more reliable predictors of aggressive joint damage than were specific HLA antigens. However, HLA antigens seemed to modify the expression of the joint disease rather than being involved in joint disease susceptibility.

Keyword
HLA antigens, Joint damage, Psoriatic arthritis
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:umu:diva-5109 (URN)10.1007/s100670200097 (DOI)
Available from: 2003-03-28 Created: 2003-03-28 Last updated: 2017-12-14Bibliographically approved
3. Analysis of five susceptibility loci in psoriatic arthritis
Open this publication in new window or tab >>Analysis of five susceptibility loci in psoriatic arthritis
Show others...
(English)Manuscript (Other academic)
Identifiers
urn:nbn:se:umu:diva-5110 (URN)
Available from: 2003-03-28 Created: 2003-03-28 Last updated: 2011-01-18Bibliographically approved
4. Renal abnormalities in a population of patients with psoriatic arthritis
Open this publication in new window or tab >>Renal abnormalities in a population of patients with psoriatic arthritis
2001 (English)In: Scandinavian Journal of Rheumatology, Vol. 30, no 5, 271-4 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:umu:diva-5111 (URN)
Available from: 2003-03-28 Created: 2003-03-28 Last updated: 2011-01-18Bibliographically approved

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