Correlation between memory B cells and bone erosion in rheumatoid arthritis / 中华风湿病学杂志

ABSTRACT

Objective:To explore the distribution characteristics of memory B cells and its relationship with bone erosion in patients with rheumatoid arthritis (RA), and to further understand the mechanism of B cells in the pathogenesis of RA.Methods:B cell subsets in peripheral blood of 200 RA patients and 50 healthy individuals were detected by flow cytometry. According to the surface markers CD19, CD27 and lgD, B cells were divided into CD19 +CD27 +lgD - switched memory B cells, CD19 +CD27 +lgD + non-switched memory B cells, CD19 +CD27 -lgD - double-negative memory B cells and CD19 +CD27 -lgD + naive B cells. B cells in RA patients with various disease activity score, course of disease and treatment were analyzed. Patients were divided into four groups according to the results of joint ultrasonography, including patients without bone erosion, patients with hand bone erosion, patients with knee bone erosion and patients with hand and knee bone erosion. The relationship between the distribution of B cell subsets, autoantibodies and RA bone erosion were analyzed. Differences between the groups were analyzed by independent-samples t test, Mann-Whitney U test and χ2 test. The analysis of variance, Kruskal-Wallis analysis were used for multi-group comparison, Spearman correlation analysis was also used for correlation analysis. Results:①RA patients showed significantly decreased non-switched memory B cells [(9.5±6.7)% vs (12.1±4.7)%, t=2.46, P=0.015] and increased double negative memory B cells [(3.8±2.5)% vs(2.7±1.3)%, t=-4.74, P<0.001] in comparison to healthy individuals. The percentage of non-switched memory B cells were decreased in RA patients with moderate disease activity [(8.4±4.7 )% vs (12.4±7.5)%, t=3.13, P=0.001] and high disease activity [(7.8±7.6)% vs (12.4±7.5)%, t=3.00, P=0.003] in comparison to those in RA patients who achieved remission. Meanwhile, the na?ve B cells [(70.3±15.0)% vs (63.9±14.6)%, t=-2.15, P=0.034] were increased in RA patients with moderate disease activity. No difference was found in RA patients with different disease courses. Total B cells [(4.8±2.9)% vs (7.2±4.1)%, t=-3.24, P=0.001], non-switched memory B cells (7.6±4.3)% vs (10.0±7.1)%, t=-2.63, P=0.010) in RA patients who received prednisone treatment were decreased, while double-negative memory B cells (4.9±3.0)% vs (3.6±2.3)%, t=-2.79, P=0.006] were increased compared with those in RA patients without prednisone treatment. Non-switched memory B cells was decreased in RA patients with hand and knee erosion compared with RA patients without erosion [6.8%(2.5%, 9.5%) vs 9.7%(5.5%, 17.5%), Z=-2.12, P=0.034]. Double negative memory B cells in subgroup with keen erosion [3.3%(2.7%, 5.0%) vs 2.6%(1.9%, 3.8%), Z=-2.09, P=0.036]as well as with hand and knee erosion [3.9%(2.3%, 5.6%) vs 2.6%(1.9%, 3.8%), Z=-2.41, P=0.016] were higher than those in patients without erosion. In addition, higher serum RF level was found in subgroup RA patients with hand and knee erosion compared with subgroup of RA patients without erosion [141.0 (38.0, 874.0) U/ml vs 53.5 (10.0, 106.0)U/ml, Z=-2.07, P=0.039]. Meanwhile, the positive rate of ACPA in RA patients with bone erosion of hand was significantly higher than that of RA patients without bone erosion [81%(52/64) vs 64%(38/59), χ2=4.44, P=0.043). Conclusions:The results suggest that the increase of double negative memory B cells, the decrease of non-switched memory B cells and higher level of autoantibodies may closely relate to bone erosion of RA, which may be one of the pathogenesis of disability in RA.