Blood concentrations of hydroxychloroquine and its desethyl derivative correlate negatively with the percentage of CD45RO+ cells among CD4+ lymphocytes in hydroxychloroquine-treated lupus patients.
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.
Sailler
Laurent
L
Service de Pharmacologie Clinique, Unité de Pharmacoépidémiologie EA3696, INSERM IFR 126, Faculte de Médecine, Université Paul Sabatier 31000 Toulouse, France. sailler.l@chu-toulouse.fr
Puissant
Bénédicte
B
Méliani
Pascal
P
Castex
Jean Olivier
JO
Saivin
Sylvie
S
Adoue
D
D
Fournie
B
B
Arlet
Philippe
P
Montastruc
Jean-Louis
JL
Lapeyre-Mestre
Maryse
M
Pourrat
Jacques
J
Blancher
Antoine
A
D000328:Adult; D018501:Antirheumatic Agents / Q000097:blood* / Q000378:metabolism / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006886:Hydroxychloroquine / Q000031:analogs & derivatives* / Q000097:blood* / Q000378:metabolism / Q000627:therapeutic use; D017493:Leukocyte Common Antigens; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000188:drug therapy; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects*
D018501:Antirheumatic Agents; D006886:Hydroxychloroquine; C049283:cletoquine; D017493:Leukocyte Common Antigens