Clinical and Molecular Evidence for Association of SLE with parvovirus B19

Abstract

In addition to genetic and environmental factors, viruses have been suspected as causes and/or contributors to human autoimmune diseases, although direct evidence for the association is generally lacking. Parvovirus B19, the cause of Fifth disease in childhood, and possible trigger in the spectrum of autoimmune diseases in adults, has emerged as one of the central viral candidates within the last few years. In this article we propose a possible model for parvovirus B19 association with systemic lupus erythematosus (SLE). The basis for our model is the secretion of hydrolyzing anti-ssDNA autoantibodies in 30-70% of cases with SLE, which in turn can either hydrolyze viral B19 ssDNA in blood and other fluids, or intranuclear, replicated viral ssDNA after re-activation and translocation of the virus into the nucleus of the host permissive cells. Both mechanisms contribute to perpetuation and maintenance of a 'vicious cycle' with concomitant flares in SLE, and involve inevitable TLR9 sensitization and genetic switch for anti-ssDNA autoantibody production from activated B cells in individuals prone to triggering. This model strongly suggests a major potential impact upon early prevention (vaccination) and targeted therapy of this subclass within the SLE spectrum of diseases. Incorporated in this new concept is an innovative idea for developing the tool for more precise (individualized) diagnosis, prevention, and therapy.

Selfness-nonselfness in designing an anti-B19 erythrovirus vaccine

“…In a few cases, the level of similarity is reflected in hundreds or thousands of exact pentapeptide matches. Examples include the low-complexity pentapeptides VP1 95-99 SSSSS (1803 occurrences in the human proteome) and VP1 241-245 /VP2 [14][15][16][17][18] GGGGS (783 occurrences in the human proteome) (Fig. 1).…”

“…1,2 In immunocompromised or hemolytic subjects, clinical manifestations following B19 infection include polyarthropathy, 3 hematological disorders, such as red cell aplasia and chronic anemia, 4 thrombocytopenia 5 and neutropenia, 6 myocarditis, 7 hepatitis, 8 neurologic diseases, [9][10][11] hyperthyroidism and thyroid cancer pathogenesis/progression, 12,13 glomerulonephritis, 14,15 and systemic lupus erythematosus. 16 On the whole, B19 infection may lead to disorders exhibiting striking similarities with systemic autoimmune diseases, and can be associated with elevated serum autoantibody titers. 17 The wide spectrum of diseases linked to B19 and the risk of infection due to the many modalities of B19 transmission (from mother to fetus, via the respiratory route, and by transfusion of blood-derived products) 1,18 has stimulated the search for anti-B19 vaccines.…”

“…It is also of note that a number of pentapeptides unique to the virus are consecutively overlapping, thus forming long peptide sequences that may be particularly useful in anti-B19 vaccine formulations. The following fragments are formed by consecutive overlapping pentapeptides with no similarity to human proteins: NS aa 16 Relationship between low-similarity peptide sequences and B19 erythrovirus epitopes. To determine whether a relationship exists between sequences with low similarity to the human proteome and B19 erythrovirus immunogenicity in the human host, we analyzed the similarity levels of experimentally validated, B19-derived epitopes currently cataloged at the IEDB.…”

CXCL13 as a new biomarker of systemic lupus erythematosus and lupus nephritis – from bench to bedside?

“…Regarding environmental factors, it is known that ultraviolet light (UVB), various drugs, pollutants and vaccinations are triggers of SLE onset [11]. Furthermore, vitamin D deficiency and viruses such as Epstein-Barr virus (EBV), human herpes virus 8 (HHV 8), parvovirus B19 and human papilloma virus (HPV) are associated with SLE [12][13][14]. There is also growing evidence that cigarette smoking may induce a bs_bs_banner Clinical and Experimental Immunology REVIEW ARTICLE doi:10.1111/cei.12439…”

Avaliação diagnóstica das infecções por vírus Epstein-Barr, parvovírus B19 e vírus linfotrópico de células T humanas em pacientes portadores de lúpus eritematoso sistêmico em hospital de referência do Estado do Pará, Brasil

“…O mecanismo para a associação do B19 com LES pode ser resultante da secreção de autoanticorpos anti-DNAfs hidrolizantes, resultantes da resposta ao DNAfs viral replicante. Esse processo causaria a morte celular, expondo o sistema imune a um novo conjunto de antígenos e assim manteria a doença ativa 32 . Outros mecanismos propostos para a ação do B19 incluem a citotoxicidade da proteína NS1, levando à apoptose 33 , reação cruzada do anticorpo anti-B19 IgG com autoantígenos humanos 34 e produção de citocinas pró-inflamatórias 27,35,36,37 .…”