In the past few years considerable advances have been made in the genetics of susceptibility to rheumatoid arthritis (RA). For decades the HLA-DRB1 alleles were the only extensively replicated genetic factor, but more genetic risk factors have now been identified that predispose to RA. Interestingly, several of the observed genetic variants conferred risk to anticitrulline-peptide antibody (ACP...

OBJECTIVES Anticyclic citrullinated protein antibodies (ACPA) are highly specific of rheumatoid arthritis (RA). However, they have also been detected in 5-10% of primary Sjögren's syndrome (pSS). We compared ACPA-positive and negative patients with pSS and assessed the risk of evolution to RA. PATIENTS AND METHODS ACPA-positive and negative patients with pSS were included in this study. For A...

Autoreactive B cells have a central role in the pathogenesis of rheumatoid arthritis (RA), and recent findings have proposed that anti-citrullinated protein autoantibodies (ACPA) may be directly pathogenic. Herein, we demonstrate the frequency of variable-region glycosylation in single-cell cloned mAbs. A total of 14 ACPA mAbs were evaluated for predicted N-linked glycosylation motifs in silico...

Francisella tularensis is a Tier 1 bioterror threat and the intracellular pathogen responsible for tularemia in humans and animals. Upon entry into the host, Francisella uses multiple mechanisms to evade killing. Our previous studies have shown that after entering its primary cellular host, the macrophage, Francisella immediately suppresses the oxidative burst by secreting a series of acid phos...

BACKGROUND Interstitial lung disease (ILD) is associated with high morbidity and mortality in rheumatoid arthritis (RA). Citrullinated proteins are observed in RA lung tissues; however, the association of specific anticitrullinated peptide antibodies (ACPA) with ILD in RA is unknown. METHODS RA patients underwent multidetector CT (MDCT) of the chest, from which ILD features and a semiquantita...

Early diagnosis and treatment of rheumatoid arthritis (RA) is necessary to prevent joint damage and long-term disability. High rates of false-negative and false-positive results of the rheumatoid factor (RF) test make it generally unhelpful in the early diagnosis of RA. A new clinical test for RA--the anti-citrullinated peptide antibody (ACPA) test--is now widely available in Australia. Owing t...

Recent findings have highlighted the potential initiation of ACPA in sites away from the joint. Periodontitis is an example of this concept. This process in the gums appears to be independent of smoking, the main environmental risk factor for ACPA-positive RA. There is extensive literature regarding the potential role of smoking in the pathogenesis of ACPA-positive RA. As a consequence of this ...

OBJECTIVE To analyse the relationship between rheumatoid factor (RF) titre, smoking and HLA-DRB1 alleles coding a "shared epitope" (SE) in relation to anti-citrullinated protein antibody (ACPA) positivity in rheumatoid arthritis (RA). METHODS RA patients (n = 658) attending rheumatology clinics in Cornwall, UK (cohort 1) were stratified according to RF and ACPA titre, and smoking pack years a...

Autoimmune responses against posttranslationally modified antigens are a hallmark of several autoimmune diseases. For example, antibodies against citrullinated protein antigens (ACPA) have shown their relevance for the prognosis and diagnosis of rheumatoid arthritis (RA), and have been implicated in disease pathogenesis. It is conceivable that other autoantibody systems, recognizing other postt...

Control of anthrax toxin and capsule synthesis, the two major virulence factors of Bacillus anthracis, has been associated with two regulatory genes, atxA and acpA, located on virulence plasmids pXO1 and pXO2, respectively. We used transcriptional profiling to determine whether atxA and/or acpA control genes other than those already described and to investigate functional similarities of the re...