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Open Access Highly Accessed Research article

Mannose-binding lectin deficiency is associated with early onset of polyarticular juvenile rheumatoid arthritis: a cohort study

Koert M Dolman12, Nannette Brouwer2, Florine NJ Frakking1*, Berit Flatø3, Paul P Tak4, Taco W Kuijpers12, Øystein Førre3 and Anna Smerdel-Ramoya3

Author Affiliations

1 Department of Pediatric Hematology, Immunology and Infectious diseases, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Meibergdreef, Amsterdam, 1105 AZ, The Netherlands

2 Department of Blood Cell Research, Sanquin Research at CLB, and Landsteiner Laboratory, University of Amsterdam, Plesmanlaan, Amsterdam, 1066 CX, The Netherlands

3 Department of Rheumatology, Rikshospitalet University Hospital, Sognsvannsveien, Oslo, NO-0027, Norway

4 Division of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Meibergdreef, Amsterdam, 1105 AZ, The Netherlands

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Arthritis Research & Therapy 2008, 10:R32  doi:10.1186/ar2386

Published: 11 March 2008

Abstract

Background

Mannose-binding lectin (MBL) is an innate immune protein. The aim of our study was to determine whether genetically determined MBL deficiency is associated with susceptibility to juvenile rheumatoid arthritis (JRA) and whether MBL2 genotypes are associated with JRA severity.

Methods

In a retrospective cohort study of 218 patients with polyarthritis (n = 67) and oligoarthritis (n = 151), clinical and laboratory disease variables were obtained by clinical examination and chart reviews. Healthy Caucasian adults (n = 194) served as control individuals. MBL2 gene mutations were determined by Taqman analysis to identify genotypes with high, medium and low expression of MBL. Functional MBL plasma concentrations were measured using enzyme-linked immunosorbent assay. Associations between clinical and laboratory variables and MBL2 genotypes were determined by Kruskal-Wallis and χ2 tests.

Results

MBL2 genotype frequencies were similar in polyarthritis and oligoarthritis patients as compared with control individuals. MBL plasma concentrations were associated with the high, medium and low MBL genotype expression groups (P < 0.01). In polyarthritis patients, the presence of low-expressing (deficient) MBL2 genotypes was associated with early age at onset of disease (P = 0.03). In oligoarthritis patients, patients with low-expressing MBL2 genotypes were more often in remission (81%) than patients in the medium (54%) and high (56%) genotype groups (P = 0.02). The remaining clinical and laboratory variables, such as arthritis severity index, presence of radiographic erosions and antinuclear antibody positivity, were not associated with MBL2 genotypes.

Conclusion

Genetically determined MBL deficiency does not increase susceptibility to JRA, but MBL deficiency is associated with a younger age at onset of juvenile polyarthritis. On the other hand, MBL-deficient children with juvenile oligoarthritis are more often in remission. Therefore, MBL appears to play a dual role in JRA.