title: Profiling lymphocyte subpopulations in peripheral blood under efalizumab treatment of psoriasis by multi epitope ligand cartography (MELC) robot microscopy.
abstract: 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 x 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 2.4x and 2.2x, 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 3.3x). 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 x 10(9)/L up to 1.616 +/- 0.152 x 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.
authors.affiliation: Clinic for Dermatology and Venereology, Otto-von-Guericke-University, Magdeburg, Leipziger Str. 44, D-39120 Magdeburg, Germany. bernd.bonnekoh@medizin.uni-magdeburg.de
authors.forename: Bernd
authors.initials: B
authors.lastname: Bonnekoh
authors.forename: Yanina
authors.initials: Y
authors.lastname: Malykh
authors.forename: Raik
authors.initials: R
authors.lastname: Böckelmann
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bartsch
authors.forename: Ansgar J
authors.initials: AJ
authors.lastname: Pommer
authors.forename: Harald
authors.initials: H
authors.lastname: Gollnick
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD / Q000097:blood; D001665:Binding Sites; D018845:CD11 Antigens / Q000276:immunology; D040881:CD11a Antigen / Q000276:immunology*; D000939:Epitopes / Q000032:analysis; D006801:Humans; D007958:Leukocyte Count; D008024:Ligands; D016131:Lymphocyte Subsets / Q000276:immunology*; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology*; D012371:Robotics; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D018845:CD11 Antigens; D040881:CD11a Antigen; D000939:Epitopes; D008024:Ligands; C472181:efalizumab