The effect of alefacept on T-cell subsets and cells expressing NK receptors in lesional psoriatic skin: the effects of monotherapy and combination treatment with calcipotriol.
OBJECTIVE
To investigate the effect of weekly alefacept monotherapy 15 mg i.m. on epidermal hyperproliferation, keratinization, T-cell subsets and cells expressing NK receptors during 12 weeks of treatment. Furthermore, the addition of calcipotriol cream to alefacept treatment was studied and compared with alefacept monotherapy.


METHODS
Five patients participated in this study, and used weekly alefacept 15 mg i.m. combined with calcipotriol cream up to a maximum of 100 g per week. Biopsies from two lesions (one treated and another lesion not treated with calcipotriol cream) were taken at week 0 and week 12. We investigated the number of T-cell subsets (CD4, CD8, CD45RO, CD45RA, CD2, CD25), cells expressing NK receptors (CD94 and CD161), the proliferation marker Ki-67 and the keratinization marker keratin-10.


RESULTS
Alefacept monotherapy induced a statistically significant reduction of CD4+, CD45RO+ and CD2+ cells in dermis and epidermis and CD8+ cells in epidermis at week 12. Furthermore, the keratin-10 positive epidermal surface was significantly increased at week 12. The combination of alefacept and calcipotriol cream induced a statistically significant reduction of only CD4+ and CD45RO+ cells at week 12.


CONCLUSIONS
The number of memory effector T-cells in the psoriatic lesion is significantly decreased by alefacept, and calcipotriol cream does not seem to have an additional effect on this reduction. Cells expressing NK receptors are virtually not targeted by alefacept monotherapy or the combination.
Vissers
W H P M
WH
Department of Dermatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. w.vissers@derma.umcn.nl
van Duijnhoven
M
M
van Erp
P E J
PE
de Jong
E M G J
EM
van de Kerkhof
P C M
PC
D000279:Administration, Cutaneous; D000077944:Alefacept; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003879:Dermatologic Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006801:Humans; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology; D018040:Receptors, Neurokinin-1 / Q000187:drug effects*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D016176:T-Lymphocyte Subsets / Q000187:drug effects*; D016896:Treatment Outcome
D003879:Dermatologic Agents; D018040:Receptors, Neurokinin-1; D011993:Recombinant Fusion Proteins; C055085:calcipotriene; D000077944:Alefacept; D002117:Calcitriol