title: Balance of Treg versus T-effector cells during systemic treatment with adalimumab and topical treatment with calcipotriol-betamethasone dipropionate ointment.
abstract: Diminished suppressive capacity of regulatory T cells (Treg) has been demonstrated in blood and in lesional skin of psoriatic patients. Treatment with anti-TNFα restored the number and function of circulating Treg in psoriasis. We aimed to study Treg in the skin of psoriatic patients undergoing topical treatment with calcipotriol-betamethasone dipropionate (CBD) ointment (n = 12) or systemic treatment with anti-TNFα agent adalimumab (n = 10). Skin biopsies were collected from patients with chronic plaque psoriasis who responded to the above-mentioned treatments with a SUM-score improvement of at least 50% (at the end of treatment). Biopsies were processed for immunohistochemistry. As Treg function is associated with a numerical balance between Treg and effector T cells, Foxp3/CD4 ratios were calculated. It appeared that both treatments cause a significant decrease in the presence of Foxp3+ cells. However, in patients that were treated with CBD ointment, we observed lower Foxp3/CD4 ratios after 8 weeks of treatment compared to baseline (t = 0: 0.41 ± 0.08; t = 8: 0.22 ± 0.04, P = 0.033), whereas in patients who were treated with adalimumab we observed an increase of the Foxp3/CD4 ratios after 1.5 and 16 weeks of treatment compared to baseline (t = 0: 0.25 ± 0.04; t = 1.5: 0.32 ± 0.06; t = 16: 0.49 ± 0.10, P = 0.15). Based on Foxp3/CD4 ratios, we can conclude that adalimumab treated skin differs from CBD treated skin with regard to the anti-inflammatory/inflammatory balance. We suggest that, in contrast to CBD ointment, adalimumab favours local Treg function in the skin.
authors.affiliation: Department of Dermatology, Radboud university medical center, Nijmegen, The Netherlands; Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Romy R M C
authors.initials: RR
authors.lastname: Keijsers
authors.forename: Irma
authors.initials: I
authors.lastname: Joosten
authors.forename: Anke G M
authors.initials: AG
authors.lastname: Hendriks
authors.forename: Hans J P M
authors.initials: HJ
authors.lastname: Koenen
authors.forename: Piet E J
authors.initials: PE
authors.lastname: van Erp
authors.forename: Peter C M
authors.initials: PC
authors.lastname: van de Kerkhof
mesh_terms: D000068879:Adalimumab; D000287:Administration, Topical; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000737:chemistry; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001623:Betamethasone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D001706:Biopsy; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D002117:Calcitriol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009824:Ointments; D011565:Psoriasis / Q000188:drug therapy* / Q000503:physiopathology; D012867:Skin / Q000187:drug effects; D016176:T-Lymphocyte Subsets / Q000166:cytology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D061067:Antibodies, Monoclonal, Humanized; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D009824:Ointments; D014409:Tumor Necrosis Factor-alpha; C055085:calcipotriene; C011175:betamethasone-17,21-dipropionate; D001623:Betamethasone; D002117:Calcitriol; D000068879:Adalimumab
keywords: Foxp3/CD4 ratio; Treg; adalimumab; calcipotriol-betamethasone dipropionate ointment