Evidence of Site-Specific Mucosal Autoantibody Secretion in Rheumatoid Arthritis.

Objective: Anti-citrullinated protein antibodies (ACPA) have been detected in sputum and saliva, indicating that anti-modified protein antibodies (AMPA) can be produced at mucosal sites in patients with rheumatoid arthritis (RA). However, the body's largest mucosal compartment, the gut, has not yet been examined. We therefore investigated the presence of several AMPA (ACPA, anti-carbamylated protein antibodies [anti-CarP], and anti-acetylated protein antibodies [AAPA]) at different mucosal sites, including the intestinal tract.

N-linked Fc glycosylation is not required for IgG-B-cell receptor function in a GC-derived B-cell line.

IgG secreted by B cells carry asparagine N(297)-linked glycans in the fragment crystallizable (Fc) region. Changes in Fc glycosylation are related to health or disease and are functionally relevant, as IgG without Fc glycans cannot bind to Fcɣ receptors or complement factors. However, it is currently unknown whether ɣ-heavy chain (ɣHC) glycans also influence the function of membrane-bound IgG-B-cell receptors (BCR) and thus the outcome of the B-cell immune response.

In rheumatoid arthritis patients, total IgA1 and IgA2 levels are elevated: implications for the mucosal origin hypothesis.

Objective: Mucosal initiated immune responses may be involved in the pathophysiology of RA. The most abundant immunoglobulin at mucosal surfaces is IgA, of which two subclasses exist: IgA1 and IgA2. IgA2 is mainly present at mucosal sites and has been ascribed pro-inflammatory properties.

Cross-reactivity of IgM anti-modified protein antibodies in rheumatoid arthritis despite limited mutational load.

Background: Anti-modified protein antibodies (AMPA) targeting citrullinated, acetylated and/or carbamylated self-antigens are hallmarks of rheumatoid arthritis (RA). Although AMPA-IgG cross-reactivity to multiple post-translational modifications (PTMs) is evident, it is unknown whether the first responding B cells, expressing IgM, display similar characteristics or if cross-reactivity is crucially dependent on somatic hypermutation (SHM). We now studied the reactivity of (germline) AMPA-IgM to further understand the breach of B cell tolerance and to identify if cross-reactivity depends on extensive SHM.

Baseline autoantibody profile in rheumatoid arthritis is associated with early treatment response but not long-term outcomes.

Background: The autoantibody profile of seropositive rheumatoid arthritis (RA) is very diverse and consists of various isotypes and antibodies to multiple post-translational modifications. It is yet unknown whether this varying breadth of the autoantibody profile is associated with treatment outcomes. Therefore, we investigated whether the composition of the autoantibody profile in RA, as a marker of the underlying immunopathology, influences initial and long-term treatment outcomes.

The isotype and IgG subclass distribution of anti-carbamylated protein antibodies in rheumatoid arthritis patients.

Background: Anti-carbamylated protein (anti-CarP) antibodies have recently been reported to occur in around 45% of rheumatoid arthritis (RA) patients and to have prognostic and diagnostic properties. At present, the breadth and molecular make-up of the anti-CarP antibody response is ill defined. To understand the anti-CarP antibody immune response and potential immune effector mechanisms it can recruit, we determined the anti-CarP antibody isotype and IgG-subclass usage in RA patients.