P167 Overcoming rituximab resistance in autoimmune disease: back to basics
P167 Overcoming rituximab resistance in autoimmune disease: back to basics
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P167 克服自身免疫性疾病中的利妥昔单抗耐药性：回到基础
DOI：
10.1093/rheumatology/kead104.208
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发表时间：
2023
期刊：
影响因子：
5.5
通讯作者：
Shah K
中科院分区：
文献类型：
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作者：
Shah K
背景/目的先前对自身免疫性疾病中对抗CD20药物利妥昔单抗反应差的B细胞生物标志物的研究与B细胞耗竭不足有关。记忆B细胞(MBC)亚群的扩大也与较差的反应有关。方法采集6例自身免疫性风湿病患者(活动期系统性红斑狼疮和类风湿性关节炎)、6例接受利妥昔单抗治疗(RTX-T)的患者和6例健康对照(HC)的外周血标本。结果RTX-N组患者外周血中CD19+CD20-B细胞比例明显高于对照组(中位数为25.9%，HC组为1.26%)，p = 0.0022。CD19+CD20-B细胞主要为开关单核细胞(IGD-CD27+)和双阴性单核细胞(IgDCD27-)。RTX-T组所有患者(美罗华治疗后22个月的中位数)均可检测到CD19+CD20-B细胞(中位数为B细胞的52.25%)，其中大多数为转换型B细胞(中位数为4.54%，范围为0.23-74%)和DNB细胞(中位数为53.5%，范围为11.6-98.1%)。总之，我们注意到外周循环中CD19+CD20-B细胞的频率在RTX-T>；RTX-N>；HC中较高。结论我们的初步结果证实了自身免疫病患者外周血中CD19+CD20-B细胞的频率较高，特别是在利妥昔单抗治疗后，提示他们逃避了利妥昔单抗。这些主要是切换的MBC和DNB细胞亚群。考虑到这些细胞在自身免疫性疾病中参与疾病活动的潜力，针对CD19的替代策略可能有助于克服利妥昔单抗抵抗。Shah：赠款/研究支持；罗氏Glycart.C.Klein：公司任命；罗氏Glycart。股东/股权；Roche.G.剑桥：无.D.Sen：无.A.Akbar：无.D.A.伊森伯格：无.Leandro：无.V.R.雷迪：赠款/研究支持；罗氏·格利卡特，BRC UCLH。
Background/AimsPrevious research into B cell biomarkers of poor response to the anti-CD20 drug rituximab in autoimmune disease relates to insufficient B cell depletion. Expansion of memory B cell (MBC) subsets were also associated with poorer response. We investigated whether the relative expression of the target antigen CD20 on B cell subpopulations could also contribute to drug resistance.MethodsPeripheral blood samples from 6 rituximab naïve (RTX-N) patients with autoimmune rheumatic diseases (active systemic lupus erythematosus and rheumatoid arthritis), 6 patients previously treated with rituximab (RTX-T), and 6 healthy controls (HC) were obtained. B cell subpopulations were defined using the relative expression of IgD and CD27 using flow cytometry.ResultsPatients in the RTX-N group had significantly higher frequency of CD19+CD20- B cells (median=25.9% of total B cells, compared to 1.26% in HC), p = 0.0022. CD19+CD20-B cells were predominantly switched MBC (IgD-CD27+) and double negative (IgDCD27-) MBC cells. All patients in the RTX-T group (median 22 months post-rituximab) had detectable CD19+CD20- B cells (median=52.25% of total B cells), of which the majority were switched MBC (median=4.54%, range 0.23-74%) and DN B cells (median=53.5%, range 11.6-98.1%). Collectively, we noted that the frequency of CD19+CD20- B cells in peripheral circulation was higher in RTX-T>RTX-N>HC.ConclusionOur preliminary results have identified greater frequency of CD19+CD20- population of B cells in peripheral blood of patients with autoimmune disease, particularly after treatment with rituximab, suggesting that they evade rituximab. These are predominantly of the switched MBC and DN B cell subpopulations. Given the potential of these cells to contribute to disease activity in autoimmune disease, alternative strategies targeting CD19 may help overcome rituximab resistance.DisclosureK. Shah:Grants/research support; Roche Glycart.C. Klein:Corporate appointments; Roche Glycart. Shareholder/stock ownership; Roche.G. Cambridge:None.D. Sen:None.M. Castelino:None.A. Akbar:None.D.A. Isenberg:None.M. Leandro:None.V.R. Reddy:Grants/research support; Roche Glycart, BRC UCLH.