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FcγRI binds immune complex (IC) to contribute to various autoimmune diseases, but a specific blocking antibody has not been reported. Here the authors characterize two anti-FcγRI antibodies that block and replace IC-binding to FcγRI in the context of patient-derived samples or a mouse immune thrombocytopenia model to implicate potential clinical translation.

Genome-wide association analysis of gout and urate identifies 148 new loci, implicating biological pathways and prioritizing candidate genes involved in inflammatory processes.

Although anti-citrullinated protein antibodies (ACPAs) are a hallmark of rheumatoid arthritis and generally considered pathogenic, their functional relevance is incompletely understood. In this study, the authors describe an ACPA with a protective effect against antibody-induced arthritis in mice.

Although many autoimmune diseases are characterized by the presence of autoantibodies, complete characterisation of autoantibody repertoires is lacking. Here, the authors introduce an autoantigen-specific Fab profiling method to show that the autoantibody repertoire in rheumatoid arthritis is diverse yet dominated only by a few clones.

Autoantibodies targeting citrunillated proteins are common in rheumatoid arthritis patients. Here the authors show that vinculin (a human protein) and some microbial proteins are recognized by these antibodies and by CD4⁺T cells, and this response is absent in patients carrying a protective HLA allele.

IgG molecules are glycosylated at a conserved asparagine residue of their constant region, and this modification is essential for the effector functions of their soluble form, such as complement activation and binding to Fcɣ receptors. Here authors show that in a model B-cell line, neither the expression nor the function of the membrane-bound form of IgG depend on glycosylation.

The IgG sugar moiety modulates the binding of immune complexes to their Fcγ receptors resulting in pro- or anti-inflammatory response. This study shows that IgG sialylation also affects osteoclastogenesis and bone mass in mice and humans, identifying a new link between bone and the immune system.

Krönke and colleagues show that the cytokine IL-23 controls the glycosylation profile and inflammatory activity of autoantibodies through control of sialyltransferase activity in plasma cells mediated by the T_H17 subset of helper T cells.

Frameshift mutations that create arginine-rich basic tails in transcription factors and other proteins can lead to altered phase separation in the nucleolus, which in turn leads to syndromes such as brachyphalangy, polydactyly and tibial aplasia.

Seemingly contrasting genetic backgrounds in anti-citrullinated-protein antibody (ACPA)-positive and ACPA-negative rheumatoid arthritis (RA) support the notion that these are in fact two distinct disease subsets, with different underlying pathogenesis, that might need tailored treatment strategies.

New research shows that an extended autoantibody repertoire is associated with adverse clinical outcomes in patients with rheumatoid arthritis. Testing for rheumatoid factor and antibodies against citrullinated proteins is now routine in the evaluation of patients with rheumatoid arthritis; should this testing be extended to include other classes of autoantibody?

Several different autoantibody systems recognizing post-translationally modified proteins have been identified in rheumatoid arthritis, beyond the well-known rheumatoid factors and anti-citrullinated protein antibodies. This Review summarizes what is known about the presence and properties of these emerging autoantibodies, in particular those recognizing carbamylated proteins.

Robert Plenge and colleagues report the results of a meta-analysis of published genome-wide association studies that led to the identification of two previously unknown variants associated with rheumatoid arthritis.

Eli Stahl and colleagues report results of a genome-wide association study meta-analysis and replication study for rheumatoid arthritis. Their work identifies several new risk loci and highlights genetic overlap with other autoimmune diseases.

A genome-wide association study meta-analysis of more than 100,000 subjects of European and Asian ancestries reveals 42 new risk loci for rheumatoid arthritis, with follow-up studies identifying 98 biological candidate genes that are either already being targeted by drugs or could be in the future.

Soumya Raychaudhuri and colleagues demonstrate the utility of GRAIL, a software program used to prioritize results from genome-wide association studies for further replication, applied here to rheumatoid arthritis. The authors seek replication of their predictions in additional independent cohorts and report three new genetic loci associated with RA susceptibility.

Jane Worthington and colleagues use a high-density genotyping chip to identify new susceptibility loci for rheumatoid arthritis and examine genetic overlap with other autoimmune diseases. Their results increase the number of confirmed rheumatoid arthritis risk loci in individuals of European ancestry and refine the location of many previously identified association signals to single genes.

Highly specific for rheumatoid arthritis (RA), anti-citrullinated protein antibodies (ACPA) are emerging as suspects in the disease pathogenesis. Do these autoantibodies define a subtype of RA, how does their presence and maturation relate to the course and characteristics of the disease, and how can we use them to improve patient outcomes? Essential facts about ACPA are explained in this Review.

In this Review, the authors discuss the latest insights into how autoantibodies and autoreactive B cells relate to the disease process in rheumatoid arthritis, from the development of pre-disease seropositivity to the onset of overt symptoms and the maintenance of disease chronicity.

The presence of anti-citrullinated protein antibodies (ACPAs) is a useful biomarker in rheumatoid arthritis (RA). New technological advances are helping to unravel the role of the anti-citrullinated antigen response in RA pathogenesis, in particular, the contribution of ACPAs, ACPA glycosylation and ACPA-expressing B cells.

Glycosylation is a common modification that can affect protein stability and interactions. In this Review, the authors discuss the role of glycosylation in rheumatic diseases, as well as the therapeutic potential of glycosylation-based interventions.