Microbial Agents as Putative Inducers of B Cell Lymphoma in Sjögren’s Syndrome through an Impaired Epigenetic Control: The State-of-The-Art

Abstract

Introduction Understanding the mechanisms underlying the pathogenesis of Sjögren's syndrome (SS) is crucially important in order to be able to discriminate the steps that lead to B cell transformation and promptly identify the patients at risk of lymphomagenesis. The aim of this narrative review is to describe the evidence concerning the role that infections or dysbiosis plays in the epigenetic control of gene expression in SS patients and their possible involvement in B cell lymphomagenesis. Materials and Methods We searched the PubMed and Google Scholar databases and selected a total of 92 articles published during the last 25 years that describe experimental and clinical studies of the potential associations of microbiota and epigenetic aberrations with the risk of B cell lymphoma in SS patients. Results and Discussion The genetic background of SS patients is characterized by the hyperexpression of genes that are mainly involved in regulating the innate and adaptive immune responses and oncogenesis. In addition, salivary gland epithelial cells and lymphocytes both have an altered epigenetic background that enhances the activation of proinflammatory and survival pathways. Dysbiosis or chronic latent infections may tune the immune response and modify the cell epigenetic machinery in such a way as to give B lymphocytes an activated or transformed phenotype. It is also worth noting that transposable integrated retroelements may participate in the pathogenesis of SS and B cell lymphomagenesis by inducing DNA breaks, modulating cell gene expression, or generating aberrant transcripts that chronically stimulate the immune system. Conclusions Microorganisms may epigenetically modify target cells and induce their transcriptome to generate an activated or transformed phenotype. The occurrence of lymphoma in more than 15% of SS patients may be the end result of a combination of genetics, epigenetics, and dysbiosis or latent infections.

Human microbiomes in cancer development and therapy

“… 220 Microorganisms can regulate the immune response, alter epigenetic markers of cells, modify target cells, activate B lymphocytes, and cause patients with Sjogren's syndrome (SS) to develop B cell lymphoma. 221 , 222 , 223 S. aureus is closely associated with cutaneous T‐cell lymphoma and promotes the progression of this disease. 224 Staphylococcal‐toxin (a‐hemolysin) inhibits cytotoxic responses by T cells and lead to immune escape.…”

Microbiome Changes in Connective Tissue Diseases and Vasculitis: Focus on Metabolism and Inflammation

“…Microorganisms can also induce epigenetic modifications by acting on the transcriptome in target cells and affecting their phenotype [ 58 ]. In this view, the occurrence of lymphoma as a possible complication in the course of SS may be the end result of a combination of genetics, epigenetics, dysbiosis, or latent infections through modulation of the expression of key genes [ 59 ].…”

Intratracheal Poly(I:C) Exposure Accelerates the Immunological Disorder of Salivary Glands in Sjogren's-Like NOD/ShiLtJ Mice

“…Epstein-Barr virus (EBV) encoded small RNA combined with La/SSB from apoptotic salivary gland epithelial cell led to the type I IFN expression via the endosomal RNA sensor TLR3 (5,8). Numerous independent studies have tested the infections of hepatitis C virus (9), retroviruses and respiratory tract virus [Coxsackie A virus (10,11), H1N1 vaccination (12), split-virion influenza viral antigens (13)] in patients with SS.…”