HPV and systemic lupus erythematosus: a mosaic of potential crossreactions

Abstract

Etiology, pathogenesis, and immunology of systemic lupus erythematosus (SLE) form a complex, still undeciphered picture that recently has been further made complicated by a new factor of morbidity: human papillomaviruses (HPVs). Indeed, a prevalence of HPV infections has been reported among SLE patients. Searching for molecular mechanisms that might underlie and explain the relationship between HPV infection and SLE, we explored the hypothesis that immune responses following HPV infection may crossreact with proteins that, when altered, associate with SLE. Analyzing HPV L1 proteins and using Epstein-Barr virus (EBV) and human retrovirus (HERV) as controls, we found a vast peptide overlap with human proteins comprehending lupus Ku autoantigen proteins p86 and p70, lupus brain antigen 1 homolog, lupus antigen expressed in neurons and muscles, natural killer cell IgG-like receptors, complement proteins C4-A and C4-B, complement receptor CD19, and others. The multitude and heterogeneity of peptide overlaps not only further support the hypothesis that crossreactivity can represent a primum movens in SLE onset, but also provide a molecular framework to the concept of SLE as "an autoimmune mosaic syndrome." Finally, once more, it emerges the need of using the principle of peptide uniqueness as a new paradigm for safe and efficacious vaccinology.

Vaccine-induced autoimmunity: the role of molecular mimicry and immune crossreaction

“…91,92 This connection led to the conjecture that the relationship may be one of cause and effect. In two recent publications, Segal et al 93,94 raised the hypothesis that HPV may be an environmental trigger eliciting the development of SLE among genetically susceptible individuals. To assess the possible role of molecular mimicry in the relationship between virus and disease, viral peptides were examined for homology to human proteins involved in the pathogenesis of SLE.…”

Addressing HPV vaccine myths: practical information for healthcare providers

“…This has included high-profile coverage of individuals who died after HPV vaccination. 88,89 The main concerns raised about the safety of HPV vaccination have focused on death following vaccination, 88,89 autoimmune and neurological conditions, [90][91][92][93][94][95][96][97][98] and premature ovarian insufficiency (POI) or ovarian failure. [99][100][101][102][103][104][105] Addressing myth 3…”

Molecular mimicry, genetic homology, and gene sharing proteomic “molecular fingerprints” using an EBV (Epstein-Barr virus)-derived microarray as a potential diagnostic method in autoimmune disease

“…Other authors have also recently noted significant overlap between proteins in the human immune response expressed by papilloma virus, another DNA virus correlated with SLE and other human autoimmune syndromes [47][48][49][50][51]. Thus, it seems that Bgene sharing^between host immune response genes is not limited to transcription factors and virokines but may include all aspects of the host immune response.…”

“…4). If further studies confirm that virokines such as the BCL-2-encoded EBV protein are poorly antigenic due to the extensive sharing of epitopes with host cytokines, then the host would be vulnerable to the partial agonist and partial antagonist properties of the EBV-encoded proteins such as BCRF-1 acting on the IL-10 receptor, and this could suggest a paradigm for the pathogenic effects of other shared genes [47][48][49][50][51]. In addition, current studies that characterize levels of IL-10 in autoimmune syndromes may in fact be measuring a combination of viral-encoded virokines and host cytokines.…”