BACKGROUND Increased expression of toll-like receptor 4 (TLR4) and its endogenous ligands, is characteristic of rheumatoid arthritis (RA) synovitis. In this study, we evaluated how these TLR4 ligands may drive pathogenic processes and whether the fine profiling of anti-citrullinated protein antibodies (ACPA) based on their target specificity might provide a simple means to predict therapeutic b...

Rheumatoid arthritis (RA) is a complex polygenic disease characterized by progressive joint destruction. Anti-citrullinated peptide antibody (ACPA) is the most specific autoantibody for RA. Genetic polymorphisms in the PADI4 gene, encoding citrullinating enzyme peptidylarginine deiminase 4 (PADI4), have been associated with susceptibility to RA [1,2]. They have also been reported to be associat...

This study was undertaken to develop a novel anti-citrullinated peptide antibody (ACPA) and to investigate its arthritogenicity in a collagen-induced arthritis (CIA) model. The novel ACPA, 12G1, was developed by injecting cyclic citrullinated antigen in mice and subsequently hybridizing the B cells producing citrullinated peptide-specific antibodies with a myeloma cell line. The arthritic joint...

The intracellular pathogen Francisella tularensis is the causative agent of tularemia, a zoonosis that can affect humans with potentially lethal consequences. Essential to Francisella virulence is its ability to survive and proliferate within phagocytes through phagosomal escape and cytosolic replication. Francisella spp. encode a variety of acid phosphatases, whose roles in phagosomal escape a...

Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes severe joint pain and eventually joint deformity. Recent large cohort studies and the rapid progression of genotyping platforms have enabled identification of more than 30 susceptibility genes for RA. HLA is the major genetic determinant for RA for which a shared epitope hypothesis (70th-74th amino acids of HLA-DRβ chain dete...

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease. Certain HLA-DRB1 "shared-epitope" alleles are reported to be positively associated with increased RA susceptibility, whereas some of the other alleles may be negatively associated. However, studies on the latter are rare. Here, we focus on the protective effects of DRB1 alleles in Japanese RA patients in an association study....

Two subtypes of the cannabinoid receptor (CB1 and CB2) are expressed in mammalian tissues. Although selective antagonists are available for each of the subtypes, most of the available cannabinoid agonists bind to both CB1 and CB2 with similar affinities. We have synthesized two analogs of N-arachidonylethanolamine (AEA), arachidonylcyclopropylamide (ACPA) and arachidonyl-2-chloroethylamide (ACE...

INTRODUCTION Previous studies have provided inconsistent results on whether variants in the MBL2 gene, coding for the complement-activating mannan-binding lectin (MBL) protein, associate with rheumatoid arthritis (RA). We re-evaluated this in context of the main environmental and genetic risk factors (smoking, HLA-DRB1 'shared epitope' (SE), PTPN22*620W), which predispose to rheumatoid factor (...

OBJECTIVE To determine the most effective treatment strategy among anticitrullinated protein antibodies (ACPA)-negative patients with early rheumatoid arthritis. METHODS In the BeSt study, 184 ACPA-negative patients were randomised to: (1) sequential monotherapy, (2) step-up therapy, (3) initial combination including prednisone, (4) initial combination including infliximab. Treatment was targ...