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.     

Mannose-binding lectin does not explain the course and outcome of pregnancy in rheumatoid arthritis

Introduction  

Rheumatoid 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.     

Circulating immune complexes contain citrullinated fibrinogen in rheumatoid arthritis

Introduction  

There is increasing evidence that autoantibodies and immune complexes (ICs) contribute to synovitis in rheumatoid arthritis (RA), yet the autoantigens incorporated in ICs in RA remain incompletely characterised.     

Mannose Binding Lectin and Susceptibility to Rheumatoid Arthritis in Brazilian Patients and Their Relatives

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.     

No evidence of major effects in several Toll-like receptor gene polymorphisms in rheumatoid arthritis

Introduction  

The objective was to study the potential genetic contribution of Toll-like receptor (TLR) genes in rheumatoid arthritis (RA). TLRs bind to pathogen-associated molecular patterns, and TLR genes influence both proinflammatory cytokine production and autoimmune responses. Host–pathogen interactions are involved in RA physiopathology.     

Association of common polymorphisms in known susceptibility genes with rheumatoid arthritis in a Slovak population using osteoarthritis patients as controls

Introduction  

Both genetic and environmental factors contribute to rheumatoid arthritis (RA), a common and complex autoimmune disease. As well as the major susceptibility gene HLA-DRB1, recent genome-wide and candidate-gene studies reported additional evidence for association of single nucleotide polymorphism (SNP) markers in the PTPN22, STAT4, OLIG3/TNFAIP3 and TRAF1/C5 loci with RA. This study was initiated to investigate the association between defined genetic markers and RA in a Slovak population. In contrast to recent studies, we included intensively-characterized osteoarthritis (OA) patients as controls.     

Dual role of interleukin-17 in pannus growth and osteoclastogenesis in rheumatoid arthritis

Introduction  

In a murine model, interleukin (IL)-17 plays a critical role in the pathogenesis of arthritis. There are controversies, however, regarding whether IL-17 is a proinflammatory mediator in rheumatoid arthritis (RA). We previously established an ex vivo cellular model using synovial tissue (ST)-derived inflammatory cells, which reproduced pannus-like tissue growth and osteoclastic activity in vitro. Using this model, we investigated the effects of IL-17 on pannus growth and osteoclastogenesis in RA.     

Advanced glycation endproducts are increased in rheumatoid arthritis patients with controlled disease

Introduction  

Advanced glycation end products (AGEs) are produced and can accumulate during chronic inflammation, as might be present in patients with rheumatoid arthritis (RA). AGEs are involved in the development of cardiovascular disease. The aim of this study is to evaluate whether AGEs are increased in patients with long-standing RA and whether AGE accumulation is related to disease activity, disease severity and measures of (premature) atherosclerosis, such as endothelial activation, endothelial dysfunction and intima media thickness (IMT).     

Influence of HLA DRB1 alleles in the susceptibility of rheumatoid arthritis and the regulation of antibodies against citrullinated proteins and rheumatoid factor

Introduction  

The purpose of this study was to investigate the association between HLA-DRB1 alleles with susceptibility to rheumatoid arthritis (RA) and production of antibodies against citrullinated proteins (ACPA) and rheumatoid factor (RF).     

Low copy number of the FCGR3B gene and rheumatoid arthritis: a case-control study and meta-analysis

Introduction  

Low copy number (CN) of the Fc gamma receptor 3B (FCGR3B) gene has been associated with systemic autoimmune disease. This receptor for IgG is present almost exclusively on neutrophils and plays a role in their interaction with immune complexes. At present the relationship between FCGR3B and rheumatoid arthritis (RA) is unclear. The aim of the present study was to investigate whether low CN of the FCGR3B gene is associated with susceptibility to RA.     

Peptidyl arginine deiminase type IV (<Emphasis Type="Italic">PADI4</Emphasis>) haplotypes interact with shared epitope regardless of anti-cyclic citrullinated peptide antibody or erosive joint status in rheumatoid arthritis: a case control study

Introduction  

Anti-cyclic citrullinated peptide autoantibodies (anti-CCP) are the most specific serologic marker for rheumatoid arthritis (RA). Genetic polymorphisms in a citrullinating (or deiminating) enzyme, peptidyl arginine deiminase type IV (PADI4) have been reproducibly associated with RA susceptibility in several populations. We investigated whether PADI4 polymorphisms contribute to anti-CCP-negative as well as -positive RA, whether they influence disease severity (erosive joint status), and whether they interact with two major risk factors for RA, Human Leukocyte Antigen-DRB1 (HLA-DRB1) shared epitope (SE) alleles and smoking, depending on anti-CCP and erosive joint status.     

S-Nitrosylation of mannose binding lectin regulates its functional activities and the formation of autoantibody in rheumatoid arthritis

The possibility of post-translational modifications of mannose binding lectin (MBL) leading to functional impairment of the MBL pathway and the presence of anti-MBL autoantibodies were reported earlier in rheumatoid arthritis (RA). MBL was observed to be S-nitrosylated (S-nitrosated) in vitro. HepG2 cells were stimulated with 10% synovial fluid from RA patients to produce increased levels of MBL and nitric oxide. Under these experimental conditions MBL was observed to be S-nitrosated using biotin switch assay. The plasma of RA patients was also found to contain higher levels of S-nitrosylated MBL (SNO-MBL) in comparison to the healthy controls. Functional activities of SNO-MBL were compared with normal MBL. Mannan binding and C4 deposition ability of MBL was found to decrease after S-nitrosylation. It was also observed that S-nitrosylation of MBL leads to a decrease in the bacterial phagocytosis and apoptotic cell binding as measured by fluorescence microscopy and FACS analysis. These results indicate that the carbohydrate binding ability of MBL was affected by S-nitrosylation (S-nitrosation). High levels of anti-MBL autoantibodies were detected against SNO-MBL in plasma of RA patients in comparison to normal MBL suggesting a role of SNO-MBL in generation of autoantibodies in RA patients.     

A1298C polymorphism in the <Emphasis Type="Italic">MTHFR</Emphasis>gene predisposes to cardiovascular risk in rheumatoid arthritis

Introduction  

We determined the contribution of the methylene tetrahydrofolate reductase (MTHFR) 677 C>T and 1298 A>C gene polymorphisms to the susceptibility to rheumatoid arthritis (RA). We also assessed whether these two MTHFR gene polymorphisms may be implicated in the development of cardiovascular (CV) events and subclinical atherosclerosis manifested by the presence of endothelial dysfunction, in a series of Spanish patients with RA.     

The usefulness of magnetic resonance imaging of the hand and wrist in very early rheumatoid arthritis

Introduction  

Magnetic resonance imaging (MRI) was used to study the hand and wrist in very early rheumatoid arthritis (RA), and the results were compared with early and established disease.     

Complex genetic predisposition in adult and juvenile rheumatoid arthritis

Background  

Rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA) are complex multifactorial diseases caused by environmental influences and an unknown number of predisposing genes. The present study was undertaken in order to investigate association of polymorphisms in candidate genes with RA and JRA in German subjects.     

Diagnostic properties of metabolic perturbations in rheumatoid arthritis

Introduction  

The aim of this study was to assess the feasibility of diagnosing early rheumatoid arthritis (RA) by measuring selected metabolic biomarkers.     

Validation of rheumatoid arthritis diagnoses in health care utilization data

Introduction  

Health care utilization databases have been increasingly used for studies of rheumatoid arthritis (RA). However, the accuracy of RA diagnoses in these data has been inconsistent.     

Primary care physicians' perspectives towards managing rheumatoid arthritis: room for improvement

Introduction  

Many people with rheumatoid arthritis (RA) do not receive care from a rheumatologist. We surveyed primary care physicians (PCPs) to better understand their attitudes, knowledge, and practices regarding the optimal treatment of RA.     

Promoter polymorphisms in the chitinase 3-like 1 gene influence the serum concentration of YKL-40 in Danish patients with rheumatoid arthritis and in healthy subjects

Introduction  

The present study investigates the association between single nucleotide polymorphisms (SNPs) in the chitinase 3-like 1 (CHI3L1) gene and serum concentrations of YKL-40 in Danish patients with rheumatoid arthritis (RA) and healthy controls as well as the association with RA in the Danish population. The CHI3L1 gene is located on chromosome 1q32.1 and encodes the YKL-40 glycoprotein. YKL-40 concentrations are elevated in the serum of patients with RA compared to healthy subjects, and YKL-40 has been suggested to be an auto-antigen and may play a role in development of RA and in inflammation.     

Immediate determination of ACPA and rheumatoid factor - a novel point of care test for detection of anti-MCV antibodies and rheumatoid factor using a lateral-flow immunoassay

Introduction  

Autoantibodies against mutated and citrullinated vimentin (MCV) represent a novel diagnostic marker for rheumatoid arthritis (RA). Recently, an increased sensitivity for anti-MCV compared to autoantibodies against cyclic citrullinated peptides (anti-CCP2) was shown in cohorts of patients with early RA and established disease.