Sentís Alexis, Diekmann Fritz, Llobell Arturo, de Moner Noemí, Espinosa Gerard, Yagüe Jordi, Campistol Josep Maria, Mirapeix Eduard, Juan Manel
Nephrology and Renal Transplantation Service, Hospital Clínic, Universitat de Barcelona, 08036, Barcelona, Spain.
Nephrology and Renal Transplantation Service, Hospital Clínic, Universitat de Barcelona, 08036, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIPABS), Barcelona, Spain; Facultat de Medicina, Universitat de Barcelona, 08036, Barcelona, Spain.
Immunobiology. 2017 Apr;222(4):620-630. doi: 10.1016/j.imbio.2016.11.011. Epub 2016 Nov 17.
The main objective of this study is to describe qualitatively and quantitatively the different immune lymphocyte phenotypes of patients with renal disease after treatment with anti-CD20.
Two cohorts of transplanted and autoimmune kidney patients were compared: (1) Those who began treatment with Rituximab, matched (for sex, age and general clinical parameters) with (2) Non-treated control kidney patients. Different analyses were performed: (A) B-lymphocyte subpopulations; (B) T-cell subpopulations; (C) serum levels of BAFF, APRIL, Rituximab and anti-Rituximab; (D) rs396991 polymorphism of CD16a and at different time points for each type of analysis: (i) at baseline, (ii) day 15, (iii) at three and (iv) six months post-antiCD20.
(A) A depletion of all B cell subsets analysed was observed preferentially decreasing the CD40memory B-cells, switched memory cells and plasmablasts. (B) A significant decreased percentage of CD4T-lymphocytes was observed. A significant decrease of the percentage of memory T-cells and an increase in naïve T-cells was also observed. (C) A significant increase for APRIL was observed, as well as a positive correlation between the APRIL levels, and the differential of B-cells. (D) The presence of CD16a Valine-variant induced greater changes in the variations of total T-cell and T-naïve subpopulations.
Our results highlight that the treatment of renal disease with Rituximab affects T-cells, particularly naïve/memory balance, while APRIL could be also a secondary marker of this treatment. The sequential analysis of phenotypic alterations of B- and T-cells could help patient management, although further studies to identify periods of remission or clinical relapse are warranted.
本研究的主要目的是定性和定量描述接受抗CD20治疗后肾病患者的不同免疫淋巴细胞表型。
比较了两组移植和自身免疫性肾病患者:(1)开始使用利妥昔单抗治疗的患者,与(2)未治疗的对照肾病患者进行性别、年龄和一般临床参数匹配。进行了不同的分析:(A)B淋巴细胞亚群;(B)T细胞亚群;(C)血清中BAFF、APRIL、利妥昔单抗和抗利妥昔单抗的水平;(D)CD16a的rs396991多态性,以及每种分析类型在不同时间点的情况:(i)基线时,(ii)第15天,(iii)抗CD20治疗后三个月和(iv)六个月。
(A)观察到所有分析的B细胞亚群均有耗竭,优先减少了CD40记忆B细胞、转换记忆细胞和成浆细胞。(B)观察到CD4 T淋巴细胞百分比显著下降。记忆T细胞百分比也显著下降,而幼稚T细胞增加。(C)观察到APRIL显著增加,且APRIL水平与B细胞差异之间存在正相关。(D)CD16a缬氨酸变体的存在导致总T细胞和幼稚T细胞亚群变化的更大改变。
我们的结果突出表明,用利妥昔单抗治疗肾病会影响T细胞,特别是幼稚/记忆平衡,而APRIL也可能是这种治疗的次要标志物。对B细胞和T细胞表型改变的序贯分析有助于患者管理,尽管有必要进行进一步研究以确定缓解期或临床复发期。