在接受羟氯喹治疗的狼疮患者中，羟氯喹及其去乙基衍生物的血药浓度与CD4⁺淋巴细胞中CD45RO⁺细胞的百分比呈负相关。

Blood concentrations of hydroxychloroquine and its desethyl derivative correlate negatively with the percentage of CD45RO+ cells among CD4+ lymphocytes in hydroxychloroquine-treated lupus patients.

作者信息

Sailler Laurent, Puissant Bénédicte, Méliani Pascal, Castex Jean Olivier, Saivin Sylvie, Adoue D, Fournie B, Arlet Philippe, Montastruc Jean-Louis, Lapeyre-Mestre Maryse, Pourrat Jacques, Blancher Antoine

机构信息

Service de Pharmacologie Clinique, Unité de Pharmacoépidémiologie EA3696, INSERM IFR 126, Faculte de Médecine, Université Paul Sabatier 31000 Toulouse, France.

出版信息

Ann N Y Acad Sci. 2007 Jun;1108:41-50. doi: 10.1196/annals.1422.005.

DOI:10.1196/annals.1422.005

PMID:17893969

Abstract

The objective of the study was to investigate the influence of the blood concentrations of hydroxychloroquine ([HCQ]) and its derivative desethylhydroxychloroquine ([DHCQ]) on lymphocyte activation or differentiation in HCQ-treated lupus patients. We studied the correlations between [HCQ], [DHCQ], and the frequency of various lymphocyte subsets in 58 HCQ-treated lupus patients (mean HCQ dose: 4.93 +/- 1.58 mg/kg/day; mean duration of the disease: 122 +/- 64 months). [HCQ] and [DHCQ] were determined by high-performance liquid chromatography (HPLC). Lymphocyte markers were studied by flow cytometry using monoclonal anti-CD3, -CD4, -CD8, -CD25, -DR, -CD45RA, -CD45RO, -CD19, -CD38, and -CD86 antibodies. sIL2-R serum concentrations were measured by enzyme-linked immunosorbent assay (ELISA). [HCQ] and [DHCQ] were 599.9 ng/mL (median: 529.5; range: 55-1935) and 353.43 (median: 286 ng/mL; range: 118-1090). In a multiple regression analysis, [HCQ] and [DHCQ] were associated with the HCQ prescribed dose in mg/kg/day (P = 0.0002 and P = 0.03) and with compliance to the treatment (P = 0.004 and P = 0.03). We found a negative correlation between [HCQ], [DHCQ], and the CD45RO+ cell frequency among CD3+CD4+ cells (P = 0.03 and P = 0.007, respectively). Other lymphocyte subset markers (LSMs) and sIL2-R concentrations were not significantly associated with [HCQ] or [DHCQ]. In the multiple regression analysis, CD45RO+ expression was negatively influenced by [HCQ] (P = 0.005), and positively influenced by smoking habits (P = 0.005) and age (P = 0.005). Similar results were found in the multivariate model including [DHCQ]. Disease activity and taking more than 10 mg/day of corticosteroids or an immunosuppressive drug did not influence CD45RO+ expression. Lupus patients had less CD3+CD4+CD45RO+ cells than controls (P = 0.03). In lupus patients, HCQ and DHCQ may alter the generation or the blood circulation of CD4+CD45RO+ lymphocytes in a concentration-dependent pattern.

摘要

本研究的目的是调查羟氯喹（[HCQ]）及其衍生物去乙基羟氯喹（[DHCQ]）的血药浓度对接受羟氯喹治疗的狼疮患者淋巴细胞激活或分化的影响。我们研究了58例接受羟氯喹治疗的狼疮患者（平均羟氯喹剂量：4.93±1.58mg/kg/天；平均病程：122±64个月）中[HCQ]、[DHCQ]与各种淋巴细胞亚群频率之间的相关性。[HCQ]和[DHCQ]通过高效液相色谱法（HPLC）测定。使用单克隆抗CD3、-CD4、-CD8、-CD25、-DR、-CD45RA、-CD45RO、-CD19、-CD38和-CD86抗体，通过流式细胞术研究淋巴细胞标志物。通过酶联免疫吸附测定（ELISA）测量血清可溶性白细胞介素2受体（sIL2-R）浓度。[HCQ]和[DHCQ]分别为599.9ng/mL（中位数：529.5；范围：55 - 1935）和353.43（中位数：286ng/mL；范围：118 - 1090）。在多元回归分析中，[HCQ]和[DHCQ]与以mg/kg/天为单位的羟氯喹规定剂量相关（P = 0.0002和P = 0.03），并与治疗依从性相关（P = 0.004和P = 0.03）。我们发现[HCQ]、[DHCQ]与CD3 + CD4 +细胞中CD45RO +细胞频率之间呈负相关（分别为P = 0.03和P = 0.007）。其他淋巴细胞亚群标志物（LSMs）和sIL2-R浓度与[HCQ]或[DHCQ]无显著相关性。在多元回归分析中，CD45RO +表达受[HCQ]的负面影响（P = 0.005），受吸烟习惯（P = 0.005）和年龄（P = 0.005）的正面影响。在包含[DHCQ]的多变量模型中发现了类似结果。疾病活动以及每天服用超过10mg的皮质类固醇或免疫抑制药物不影响CD45RO +表达。狼疮患者的CD3 + CD4 + CD45RO +细胞比对照组少（P = 0.03）。在狼疮患者中，羟氯喹和去乙基羟氯喹可能以浓度依赖的方式改变CD4 + CD45RO +淋巴细胞的生成或血液循环。