Cladribine Alters Immune Cell Surface Molecules for Adhesion and Costimulation: Further Insights to the Mode of Action in Multiple Sclerosis

被引:11
|
作者
Moser, Tobias [1 ,2 ]
Hoepner, Lena [2 ]
Schwenker, Kerstin [1 ]
Seiberl, Michael [1 ]
Feige, Julia [1 ]
Akguen, Katja [2 ]
Haschke-Becher, Elisabeth [3 ]
Ziemssen, Tjalf [2 ]
Sellner, Johann [1 ,4 ,5 ]
机构
[1] Paracelsus Med Univ, Christian Doppler Med Ctr, Dept Neurol, A-5020 Salzburg, Austria
[2] Tech Univ Dresden, Carl Gustav Carus Univ Hosp, Multiple Sclerosis Ctr, Ctr Clin Neurosci,Dept Neurol, D-01307 Dresden, Germany
[3] Paracelsus Med Univ, Dept Lab Med, A-5020 Salzburg, Austria
[4] Tech Univ Munich, Dept Neurol, Klinikum Rechts Isar, D-80333 Munich, Germany
[5] Landesklinikum Mistelbach Ganserndorf, Dept Neurol, A-2130 Mistelbach, Austria
关键词
cladribine; multiple sclerosis; adhesion molecules; costimulatory molecules; immune cells; LFA-1; ICAM-1; CD154; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; BLOOD-BRAIN-BARRIER; T-CELLS; IMMUNOLOGICAL SYNAPSE; DISEASE-ACTIVITY; ACTIVATION; EXPRESSION; ANTIBODIES; BLOCKADE; CD44;
D O I
10.3390/cells10113116
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Cladribine (CLAD) is a deoxyadenosine analogue prodrug which is given in multiple sclerosis (MS) as two short oral treatment courses 12 months apart. Reconstitution of adaptive immune function following selective immune cell depletion is the presumed mode of action. In this exploratory study, we investigated the impact of CLAD tablets on immune cell surface molecules for adhesion (CAMs) and costimulation (CoSs) in people with MS (pwMS). We studied 18 pwMS who started treatment with CLAD and 10 healthy controls (HCs). Peripheral blood mononuclear cells were collected at baseline and every 3 months throughout a 24-month period. We analysed ICAM-1, LFA-1, CD28, HLADR, CD154, CD44, VLA-4 (CD49d/CD29), PSGL-1 and PD-1 with regard to their expression on B and T cells (T helper (Th) and cytotoxic T cells (cT)) and surface density (mean fluorescence intensity, MFI) by flow cytometry. The targeted analysis of CAM and CoS on the surface of immune cells in pwMS revealed a higher percentage of ICAM-1 (B cells, Th, cT), LFA-1 (B cells, cT), HLADR (B cells, cT), CD28 (cT) and CD154 (Th). In pwMS, we found lower frequencies of Th and cT cells expressing PSGL-1 and B cells for the inhibitory signal PD-1, whereas the surface expression of LFA-1 on cT and of HLADR on B cells was denser. Twenty-four months after the first CLAD cycle, the frequencies of B cells expressing CD44, CD29 and CD49d were lower compared with the baseline, together with decreased densities of ICAM-1, CD44 and HLADR. The rate of CD154 expressing Th cells dropped at 12 months. For cT, no changes were seen for frequency or density. Immune reconstitution by oral CLAD was associated with modification of the pro-migratory and -inflammatory surface patterns of CAMs and CoSs in immune cell subsets. This observation pertains primarily to B cells, which are key cells underlying MS pathogenesis.
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页数:18
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