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The therapeutic benefit of depleting B cells in rheumatoid arthritis (RA) has refocused attention on B cells with increasing awareness on their role in autoimmunity and their function beyond autoantibody production. The rapid increase in our comprehension of B-cell pathobiology is progressively opening novel perspectives in the area of B cell-targeted therapies with the expectation to define more specific approaches able to preserve the homeostasis of the humoral response while disrupting the pathogenic components. In parallel, B-cell activity in RA is starting to be explored in its clinical value, in search of novel biomarkers embedded in the pathogenic process that could help classifying the disease and predicting its heterogeneous outcome beyond inflammation dynamics. In this review, we summarize current knowledge on the multiple roles that B cells play in several aspects of RA. We also analyze their distribution and potential function in different anatomic compartments with specific reference to the main sites in which the disease may be sustained and exert its detrimental effects: the systemic circulation, synovium, bone marrow, and draining lymph nodes. We also highlight novel data encouraging further research in the field of biomarkers related to B cells and their regulatory factors.

BackgroundAutoantibodies such as anti-citrullinated protein antibodies (ACPA) are major risk factors for articular bone destruction from the earliest phases of rheumatoid arthritis (RA). The aim of the current study was to determine whether RA-associated autoantibodies also impact on systemic bone loss in patients with early disease.MethodsSystemic bone mineral density (BMD) was measured in the lumbar spine and the hip in 155 consecutive treatment-naïve patients with early RA (median symptom duration 13 weeks). Demographic and disease-specific parameters, including clinical disease activity, ultrasonographic (US) examination of the hands and wrists, radiographic scoring of joint damage, ACPA and rheumatoid factor (RF) levels were recorded from all patients. Reduced BMD was defined as Z score ≤ -1 SD and analysed in relation to disease-related characteristics and autoantibody subgroups.ResultsReduced BMD was found in 25.5 % of the patients in the spine and 19.4 % in the hip. Symptom duration, clinical and US disease activity, functional disability and radiographic damage did not significantly impact on spine and hip BMD loss in regression analyses adjusted for possible confounders (age, gender, menopausal status, current smoking, body mass index). In contrast, ACPA positivity (at any level) negatively affected the spine Z-score (adjusted OR (95 % CI) 2.76 (1.19 to 6.42)); the hip Z score was affected by high titres only (adjusted OR (95 % CI) 2.96 (1.15 to 7.66)). The association of ACPA with reduced BMD in the spine was confirmed even at low levels of RF (adjusted OR (95 % CI) 2.65 (1.01 to 7.24)), but was further increased by concomitant high RF (adjusted OR (95 % CI) 3.38 (1.11 to 10.34)). In contrast, Z scores in the hip were significantly reduced only in association with high ACPA and RF (adjusted OR (95 % CI) 4.96 (1.48 to 16.64)).ConclusionsSystemic BMD in patients with early RA is reduced in relation with ACPA positivity and high RF levels. This finding supports the notion that RA-associated autoimmunity may have a direct causative role in bone remodeling.