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Blood Concentrations of Hydroxychloroquine and Its Desethyl Derivative Correlate Negatively with the Percentage of CD45RO + Cells among CD4 + Lymphocytes in Hydroxychloroquine‐Treated Lupus Patients
Author(s) -
SAILLER LAURENT,
PUISSANT BÉNÉDICTE,
MÉLIANI PASCAL,
CASTEX JEAN OLIVIER,
SAIVIN SYLVIE,
ADOUE D,
FOURNIE B,
ARLET PHILIPPE,
MONTASTRUC JEANLOUIS,
LAPEYREMESTRE MARYSE,
POURRAT JACQUES,
BLANCHER ANTOINE
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1422.005
Subject(s) - hydroxychloroquine , lymphocyte , medicine , cd8 , chemistry , endocrinology , immunology , immune system , covid-19 , disease , infectious disease (medical specialty)
: 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.