AP-HP, Hôpital Pitié-Salpêtrière, Biotherapy (CIC-BTi) and Inflammation-Immunopathology-Biotherapy Department, Paris, France; Sorbonne Universités, UPMC Univ Paris, Paris, France; INSERM, UMR_S 959, Paris, France.
Sorbonne Universités, UPMC Univ Paris, Paris, France; INSERM, UMR_S 1155, Paris, France.
Kidney Int. 2017 Jul;92(1):227-237. doi: 10.1016/j.kint.2017.01.012. Epub 2017 Mar 15.
Primary membranous nephropathy (PMN) is characterized by antibodies to the podocyte, but little is known about B- and T-cell populations and their response to rituximab is controversial. To help resolve this we compared 33 lymphocyte subpopulations and 27 cytokines/chemokines in 25 patients with severe PMN and 27 age-matched healthy individuals. At baseline, patients had a significantly increased percentage of naive B-cells with significantly decreased switched and non-switched memory B-cells. There was a significantly decreased percentage of natural killer (NK) cells with an increase in the CD56CD16 NK subset. There were a significantly decreased percentage of regulatory T cells, together with an increased plasma concentration of TNF-alpha, IL-5 and IL-2RA. We then investigated 16 patients at eight days and three and six months after treatment with rituximab added to supportive therapy compared to nine patients with supportive therapy alone. After rituximab, B-cell recovery was still incomplete at six months, with persistent alterations of B-cell subsets, a significant increase of both T-regulatory (Treg) cells and NK cells, and a significant decrease of both the CD56CD16 NK subset and TNF-alpha levels. The patients who clinically responded to rituximab had a significantly lower percentage of Tregs at baseline compared to non-responders and a significantly increased percentage at day eight. Tregs remained unchanged in non-responders and in patients treated with supportive therapy alone. Thus, evaluation of Tregs might be useful for predicting early response to rituximab.
原发性膜性肾病（PMN）的特征是针对足细胞的抗体，但对 B 细胞和 T 细胞群体及其对利妥昔单抗的反应知之甚少，存在争议。为了帮助解决这个问题，我们比较了 25 例严重 PMN 患者和 27 名年龄匹配的健康个体的 33 种淋巴细胞亚群和 27 种细胞因子/趋化因子。在基线时，患者的幼稚 B 细胞百分比显著增加，而已成熟的记忆 B 细胞（包括 switched 和 non-switched 记忆 B 细胞）百分比显著降低。自然杀伤（NK）细胞百分比显著降低，CD56CD16 NK 亚群增加。调节性 T 细胞（Treg）百分比显著降低，同时 TNF-α、IL-5 和 IL-2RA 的血浆浓度增加。然后，我们在添加支持治疗的利妥昔单抗治疗后 8 天、3 个月和 6 个月时对 16 例患者进行了研究，与单独接受支持治疗的 9 例患者进行了比较。利妥昔单抗治疗后，6 个月时 B 细胞仍未完全恢复，B 细胞亚群仍持续改变，Treg 和 NK 细胞显著增加，CD56CD16 NK 亚群和 TNF-α水平显著降低。与无应答者相比，对利妥昔单抗有临床反应的患者在基线时 Treg 的百分比显著降低，而在第 8 天时 Treg 的百分比显著升高。无应答者和单独接受支持治疗的患者的 Treg 没有变化。因此，评估 Treg 可能有助于预测对利妥昔单抗的早期反应。
