Monday, November 30, 2020

LRP1/CD91 is Highly Expressed in Monocytes from Patients with Vitiligo, Even After Repigmentation.

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Abstract

Vitiligo pathophysiology is mediated by antigen‐specific cytotoxic T cells. Environmental stressors cause susceptible melanocytes to secrete damage‐associated molecular patterns (DAMPs). DAMPs are recognized by receptors such as the endocytic low‐density‐lipoprotein receptor‐related‐protein (LRP1/CD91), expressed in antigen presenting cells, which activate self‐reactive CD8+ T cells, leading to melanocyte destruction. Within this response, interferon‐gamma triggers production of cytokine CXCL10, recruiting more activated T cells causing further melanocytic damage. We hypothesized that expression of LRP1/CD91 was higher in vitiligo patients compared to non‐vitiligo individuals. And further that levels/expression of CXCL10 in plasma were linked to disease severity. We enrolled forty individuals in this study: 18 patients with vitiligo and 22 healthy volunteers. We assessed LRP1/CD91 expression and plasma CXCL10 in patients with vitiligo and healthy volunteers. Addi tionally, vitiligo patients received combined treatment for 16‐weeks following which the said parameters were reassessed. Vitiligo Area Scoring Index were calculated before and after treatment for these patients. Analysis of LRP1/CD91 MFI values in monocytes from vitiligo patients showed high surface levels of LRP1/CD91 than from healthy volunteers (10.50±0.77 vs 6.55±0.77 MFI units, p<0.001). This expression did not change after treatment. Plasma levels of CXCL10 were higher in vitiligo patients than healthy volunteers (93.78±7.73 vs 40.17±6.25 pg/mL). The patients with a good clinical response to treatment had a parallel reduction in plasma CXCL10 levels (105.8±18.44 vs 66.13±4.87 pg/mL) before and after treatment. LRP1/CD91 expression may reflect susceptibility to vitiligo. Plasma levels of CXCL10 can represent a biomarker for monitoring treatment response. LRP1 and CXCL10 may represent therapeutic targets.

IRB approval status: Reviewed and approved by Hospital de la Santa Creu I Sant Pau clinical research ethics committee identified as IIBSP‐VIT‐2015‐69

ClinicalTrials.gov identifier: NCT03249064

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