Background/Purpose: B cells are involved as central players in the pathogenesis of rheumatoid arthritis (RA). Our aim was to define whether a specific B cell subset characterizes the early phases of the disease and is associated with a peculiar RA phenotype.

Methods: 105 ERA patients (81.0% females; mean age 54.7 ± 15.2 years; 73.3% autoantibodies-AAB positive) and 30 healthy controls (HC) were studied. Baseline clinical and immunological characteristics and inflammatory status were assessed. Peripheral blood samples were analyzed by flow cytometry for the distribution of circulating B cell subsets by staining with surface markers CD19, CD45, CD38, CD27 and IgD and intracellular marker ZAP70. Plasma levels of IL-6 and BAFF were also determined with ELISAs. The expression of ZAP-70 and SYK was analized in B cells of 22 ERA patients, using the RealTime ready Assay method. 

Results: ERA patients showed a higher percentage of naïve-activate B cells and a lower percentage of memory B cells compared to HC, as confirmed by a higher ratio between Bm2+Bm2’/eBm5+Bm5 (3.4±3.5 in ERA and 1.7±0.9 in controls, p=0.003). AAB positive patients showed a higher percentage of CD19+/CD38+CD27+ (4.0±5.0%) compared to AAB negative ones (2.2±2.8%, p=0.05). The expression of ZAP-70 in B cells was similar in ERA patients and controls. Dividing patients for the AAB seropositivity, AAB+ ERA patients showed higher percentage of CD19+/ZAP70+ cells compared to AAB- (5.1±6.3 vs 2.5±2.4, p=0.01) and also to HC (2.2±1.4, p=0.05). In ERA patients, the percentage of ZAP70+ B cells correlated directly with the percentage of CD19+/IgD-CD27- cells (r=0.338, p=0.001), plasma BAFF levels (r=0.26, p=0.01) and with Anti-MCV (r=0.27, p=0.01), ACPA (r=0.23, p=0.02) and RF-IgA (r=0.28, p=0.01) AAB titers. ZAP-70 transcription in B cells of subjects seropositive for autoantibodies was significantly higher than in seronegative ones (3.4 ± 2.8 vs 1.2 ± 1.0 respectively; p=0.04), data confirmed by an higher ratio ZAP70/SYK in AB+ compared to AB- (2.9 ± 1.6 vs 1.2 ± 1.0 respectively; p=0.01). Moreover, the expression of ZAP-70 correlated positively with the expression of SYK (r=0.66, p=0.003) and showed a trend for an association with the espression of ZAP70 protein, evaluated by flow-cytometry (r=0.41, p=0.09). 

Conclusion: ZAP-70 positive B cells characterize AAB positive RA and the expression of ZAP-70 might be a possible complementary biomarker of seropositive disease.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/b-cells-in-early-rheumatoid-arthritis-zap-70-more-than-syk-characterize-seropositive-disease/