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Mannose binding lectin and susceptibility to rheumatoid arthritis in Brazilian patients and their relatives.

ABSTRACT: INTRODUCTION: Rheumatoid arthritis (RA) is a commonly occurring systemic inflammatory auto immune disease and is believed to be associated with genetic factors. The innate immune complement protein Mannose binding lectin (MBL) and their MBL2 genetic variants are associated with different infectious and autoimmune diseases. METHODS: In a Brazilian cohort, we aim to associate the functional role of circulating MBL serum levels and MBL2 variants in clinically classified patients (n?=?196) with rheumatoid arthritis including their relatives (n?=?200) and ethnicity matched healthy controls (n?=?200). MBL serum levels were measured by ELISA and functional MBL2 variants were genotyped by direct sequencing. RESULTS: The exon1+54 MBL2*B variant was significantly associated with an increased risk and the reconstructed haplotype MBL2*LYPB was associated with RA susceptibility. Circulating serum MBL levels were observed significantly lower in RA patients compared to their relatives and controls. No significant contribution of MBL levels were observed with respect to functional class, age at disease onset, disease duration and/or other clinical parameters such as nodules, secondary Sjögren syndrome, anti-CCP and rheumatoid factor. Differential distribution of serum MBL levels with functional MBL2 variants was observed in respective RA patients and their relatives. CONCLUSIONS: Our results suggest MBL levels as a possible marker for RA susceptibility in a Brazilian population.

SUBMITTER: Goeldner I

PROVIDER: S-EPMC3994105 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Mannose binding lectin and susceptibility to rheumatoid arthritis in Brazilian patients and their relatives.

Goeldner Isabela I Skare Thelma L TL Utiyama Shirley R SR Nisihara Renato M RM Tong Hoang van Hv Messias-Reason Iara J T IJ Velavan Thirumalaisamy P TP

PloS one 20140421 4

<h4>Introduction</h4>Rheumatoid arthritis (RA) is a commonly occurring systemic inflammatory auto immune disease and is believed to be associated with genetic factors. The innate immune complement protein Mannose binding lectin (MBL) and their MBL2 genetic variants are associated with different infectious and autoimmune diseases.<h4>Methods</h4>In a Brazilian cohort, we aim to associate the functional role of circulating MBL serum levels and MBL2 variants in clinically classified patients (n = 1 ...[more]

PMID: 24751721

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Project description:IntroductionRheumatoid arthritis (RA) improves during pregnancy and flares after delivery. It has been hypothesized that high levels of the complement factor mannose-binding lectin (MBL) are associated with a favourable disease course of RA by facilitating the clearance of pathogenic immunoglobulin G (IgG) lacking galactose sugar moieties. During pregnancy, increased galactosylation of IgG and simultaneously increased MBL levels can be observed, with the latter being strictly related to maternal MBL genotypes. Therefore, increased MBL levels in concert with increased IgG galactosylation may be associated with pregnancy-induced improvement of RA. The objective of this study was to investigate whether MBL genotypes are associated with changes in RA disease activity and with changes in IgG galactosylation during pregnancy and in the postpartum period. We also studied the association between MBL genotypes and pregnancy outcomes in RA.MethodsSerum from 216 patients with RA and 31 healthy controls participating in the Pregnancy-induced Amelioration of Rheumatoid Arthritis (PARA) Study was collected before, during and after pregnancy. IgG galactosylation was determined by performing matrix-assisted laser desorption/ionization time of flight mass spectrometry. Disease activity was determined using the internationally recognized Disease Activity Score 28 (DAS28). MBL genotypes were determined. The pregnancy outcome measures studied were gestational age, birth weight, miscarriage and hypertensive disorders.ResultsNo association was found between the MBL genotype groups and changes in RA disease activity (P = 0.89) or changes in IgG galactosylation (patients, P = 0.75, and controls, P = 0.54) during pregnancy and in the postpartum period. Furthermore, MBL genotype groups were not related to the studied pregnancy outcome measures.ConclusionsThis study does not provide evidence for a role for MBL in the improvement of RA during pregnancy or for a role for MBL in pregnancy outcome.

Dataset Information

Mannose binding lectin and susceptibility to rheumatoid arthritis in Brazilian patients and their relatives.

Publications

Mannose binding lectin and susceptibility to rheumatoid arthritis in Brazilian patients and their relatives.

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