P31 Modelling epidermal melanocytes behaviour during plaque psoriasis resolution

Abstract

Abstract Introduction and aims Melanocytes in the human epidermis exist in the stratum basale at a ratio of 1 melanocyte to approximately 10 keratinocytes. They do not divide, even upon ultraviolet radiation stimulation, and do not appear to apoptose. In psoriasis, this melanocyte/keratinocyte ratio is retained, despite the enormous keratinocyte hyperplasia, inferring a commensurate expansion in melanocyte number. Therefore, here we investigate whether melanocyte number is altered following the reduction of keratinocytes upon treatment of psoriasis plaques with biologic therapy. Methods Matching lesional and nonlesional epidermis sets of patients (n = 4) at day 0 and after 4 and 12 weeks of treatment were compared with healthy controls. To assess the presence of apoptotic melanocytes, the terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) assay was performed. Immunohistochemistry with microphthalmia-associated transcription factor (melanocyte marker) and Ki-67 (proliferation marker) was used to assess melanocyte proliferation. Finally, melanocyte number per mm of basal layer and melanocyte/keratinocyte ratio were estimated by image analysis using ImageJ. Results Proliferating melanocytes were detected in nonlesional and lesional samples and in resolving plaques after 4 and 12 weeks of treatment but not in healthy epidermis. Melanocyte number per mm of basal layer was significantly higher in nonlesional than lesional sections compared with healthy controls (P < 0.01) suggesting that melanocyte expansion already occurs prior to lesion establishment, revealing early melanocyte deregulation. After 4 and 12 weeks of treatment the number of melanocytes in lesional and nonlesional sections was still significantly higher than controls (P < 0.05) and had not returned to normal despite the dramatic reduction in keratinocytes. The TUNEL assay did not detect evidence of melanocyte apoptosis. Conclusions This study shows that rare melanocyte proliferation occurs in nonlesional psoriasis skin and in resolving lesional skin. Given our inability to detect apoptotic melanocytes, it remains unclear how melanocyte numbers return to normal after plaque resolution These unique findings support a role for melanocytes in psoriasis pathogenesis and encourage further investigation.