Author:
Rezabakhsh Aysa,Manjili Masoud H.,Hosseinifard Hossein,Reza Sadaie M.
Abstract
AbstractCurrent treatments are ineffective to cure or prevent occurrences of autoimmune psoriasis and psoriatic cardiovascular disease/CVD. Psoriasis is associated with deregulated expressions of human endogenous retroviruses (ERVs) variants. ERV transcripts and proteins are detected in lesioned biopsies—without assembled viral particles—in addition to antibody and T-cell responses against ERV-K dUTPase. In persons living with HIV-1, manifestations of psoriasis are exacerbated variably. These may depend on multiple factors, differences in ERVs expressions, subtypes of HIV-1, and/or epigenetics. This article represents a quantitative risk assessment and meta-analysis approach with an attempt to assess causality. We surmise that mutated ERVs trigger aberrant proliferation and differentiation of keratinocytes, which in turn induce proinflammatory polarization. Independent risk factors and/or covariates with a range of relative risk/RR ratios appear to significantly impact the development of autoimmune psoriasis or immune intolerance, plausibly through ERVs genes activity. Given the antihypertensive drug’s potential in psoriasis development, a probable role in promising either ERVs activation or perturbations in epigenetic factors is questionable. Although the correlational nature of the data based on RR ratios prevents making robust conclusions, we reckon that the likelihood of attributable risk factors for certain antihypertensive drugs may stem from their pleiotropic effects or potentials for inducing ERV-mediated dysregulation of keratinocytes and/or endothelial cells. These findings expand our knowledge regarding ERV activations and HIV-1, antihypertensive drugs use, and incidents of psoriatic disease, and call for exploring cell-specific therapies aimed at blocking or reversing mutated ERVs gene activity toward attaining stable remissions in psoriasis and associated CVD.
Publisher
Cold Spring Harbor Laboratory