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Profiling lymphocyte subpopulations in peripheral blood under efalizumab treatment of psoriasis by multi epitope ligand cartography (MELC) robot microscopy |
European Journal of Dermatology. Volume 16, Number 6, 623-35, November-December 2006, Investigative report
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Free Article
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Author(s) : Bernd Bonnekoh, Yanina Malykh, Raik Böckelmann, Sebastian Bartsch, Ansgar J Pommer, Harald Gollnick |
Summary : CD11a-blocking efalizumab has recently been approved as a systemic treatment of moderate to severe chronic plaque psoriasis. When treating 6 psoriasis patients with efalizumab over 12 weeks in the present study, we observed an overall good tolerability and 5 treatment responders characterized by a decrease of PASI from 21.3 ± 5.4 to 3.9 ± 0.6. The accompanying significant increase of peripheral blood lymphocytes from 1.9 ± 0.7 to 4.3 ± 1.0 × 10
9/L (p <\; 0.05) was analyzed by multi epitope ligand cartography (MELC) robot microscopy. Thereby a high-dimension simultaneous multiplex immunophenotyping was pursued using 39 fluorophore-labeled antibodies including labeled efalizumab and 3 other affinity reagents such as lectins. Due to efalizumab treatment there was a substantial decrease of the cellular expression of CD11a (detected by mab clone 25.3.1) and efalizumab binding sites (EfaBSs). This was paralleled by an increase of the number of EfaBS
– and EfaBS
+ lymphocytes by a factor of 2.4× and 2.2×, respectively. The latter effect was mainly derived from a subpopulation showing a low degree of EfaBS expression. Efalizumab treatment led furthermore to an increase of the numbers of CD3
+, CD4
+, CD8
+, CD44
+, CD45
+, CD45R0
+, CD45 RA
+, CD52
+, CD58
+, CD247
+, HLA-DR
+ and Sambucus nigra lectin-reactive lymphocytes (by factors from 2.0 to 3.3×). In terms of a combinatorial molecular phenotype we identified a CD3
+/CD4
+/CD44
+/CD52
+ lymphocyte subpopulation which accumulated most predominantly from 0.824 ± 0.270 × 10
9/L up to 1.616 ± 0.152 × 10
9/L under efalizumab treatment (p <\; 0.01). Thus, the current study extends the knowledge of efalizumab-dependent perturbations of recirculating blood lymphocyte subpopulations in psoriasis patients. |
Keywords : CD11a, Biologicals, Proteomics, MELC Toponomics, Multiplex Fluorescence Immunophenotyping, Cytometry |
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