title: 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.
authors.affiliation: Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center (Tel-Hashomer), Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Yahel
authors.initials: Y
authors.lastname: Segal
authors.affiliation: Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center (Tel-Hashomer), Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Shani
authors.initials: S
authors.lastname: Dahan
authors.affiliation: Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Calabrò
authors.affiliation: Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy.
authors.forename: Darja
authors.initials: D
authors.lastname: Kanduc
authors.affiliation: Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center (Tel-Hashomer), Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Shoenfel@post.tau.ac.il.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Shoenfel@post.tau.ac.il.|Department of Medicine B, Chaim Sheba Medical Center, Tel Hashomer, 52621, Ramat Gan, Israel. Shoenfel@post.tau.ac.il.
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Shoenfeld
mesh_terms: D000914:Antibodies, Viral / Q000097:blood; D018941:Antigens, CD19 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015551:Autoimmunity; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003181:Complement C4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003429:Cross Reactions; D018604:Epitope Mapping; D006801:Humans; D000072200:Ku Autoantigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000821:virology*; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D027383:Papillomaviridae / Q000276:immunology*; D030361:Papillomavirus Infections / Q000276:immunology / Q000821:virology*; D053918:Papillomavirus Vaccines / Q000276:immunology*; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D055607:Receptors, Natural Killer Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D000914:Antibodies, Viral; D018941:Antigens, CD19; D036022:Capsid Proteins; D003181:Complement C4; C114580:HPV L1 protein, Human papillomavirus; D009856:Oncogene Proteins, Viral; D053918:Papillomavirus Vaccines; D010446:Peptide Fragments; D055607:Receptors, Natural Killer Cell; D000072200:Ku Autoantigen
keywords: Crossreactivity; EBV; HERV; HPV; SLE