Abstract
BackgroundPsoriasis is a multifactorial, chronic disease of skin affecting 2-3% of the world’s population. Genetic studies of psoriasis have identified a number of susceptibility genes that are involved in anti-viral immunity. Furthermore, physiological studies have also found an increase in anti-viral proteins in psoriatic skin. These findings suggest the presence of an anti-viral state in psoriatic skin. However, the triggers for this anti-viral cascade and its consequences for host immunity are not known. Endogenous retroviruses have previously been described in many autoimmune diseases including psoriasis.MethodsIn the present study we examined the humoral immune response against human endogenous retrovirus-K (HERV-K) proteins and the cutaneous expression levels of multiple HERV-K genes in psoriasis patients and healthy controls.ResultsIn psoriatic sera we observed a significant decrease in IgM response against three HERV-K proteins: Env surface unit (SU), Env transmembrane protein (TM), and Gag capsid (CA) in comparison to sera obtained from blood bank healthy controls. A decrease in IgG response was also observed against CA. Furthermore, using quantitative RT-PCR we observed a decrease in the expression of HERV-K Env, Gag, Pol and Rec as well as ERV-9 genes in lesional psoriatic skin as compared to healthy skin.ConclusionsTogether, our results suggest that the pro-inflammatory, anti-viral state in psoriasis is associated with diminished expression of HERV-K gene transcripts and a concomitant decrease in humoral responses to HERV-K. Our results indicate that a simple model where continuous, minimally changing HERV-K expression serves as an antigenic trigger in psoriasis might not be correct and further studies are needed to decipher the possible relationship between psoriasis and HERVs.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-014-0256-4) contains supplementary material, which is available to authorized users.
Highlights
Psoriasis is a multifactorial, chronic disease of skin affecting 2-3% of the world’s population
We examined the antibody responses against the two envelope subunits encoded by the Env gene: the transmembrane protein (Env-recTM) and surface unit (Env-recSU), and the capsid encoded by Group specific antigen (Gag) (Gag-recCA)
We examined IgG responses against five Gag peptides that we have previously identified as reacting with healthy donor sera among a set of 164 overlapping “15-mer” Human Endogenous retrovirus (HERV)-K
Summary
Chronic disease of skin affecting 2-3% of the world’s population. One of the interesting findings of these studies is the observation that many of these genetic variants involve genes that are known to play important roles in anti-viral defense mechanisms. Notable among these are IL28RA, IFIH1, DDX58 [3], and RNF114 [4]. We have performed whole transcriptome analysis of psoriasis skin and found that antiviral restriction factors are strongly upregulated in psoriatic skin and not in atopic dermatitis skin (manuscript in preparation) These results suggest that psoriasis patients might have a strong cutaneous anti-viral immunity. The inciting factors and consequences of this antiviral immunity are not known
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