Mannose-binding lectin deficiency is associated with early onset of polyarticular juvenile rheumatoid arthritis: a cohort study.
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 chi2 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.


CONCLUSIONS
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.
Dolman
Koert M
KM
Department of Pediatric Hematology, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Meibergdreef, Amsterdam, 1105 AZ, The Netherlands. k.m.dolman@amc.uva.nl
Brouwer
Nannette
N
Frakking
Florine N J
FN
Flatø
Berit
B
Tak
Paul P
PP
Kuijpers
Taco W
TW
Førre
Oystein
O
Smerdel-Ramoya
Anna
A
D000293:Adolescent; D017668:Age of Onset; D001171:Arthritis, Juvenile / Q000235:genetics* / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D037601:Mannose-Binding Lectin / Q000097:blood / Q000172:deficiency* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies
C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin