Increased toll-like receptor 4 expression in thymus of myasthenic patients with thymitis and thymic involution.

Abstract

Thymic abnormalities are present in approximately 80% of myasthenia gravis (MG) patients, and the thymus seems to be the main site of autosensitization to the acetylcholine receptor. In view of findings that the innate immune system can generate an autoimmune response, we studied the expression of Toll-like receptors (TLRs) 2 to 5, key components of innate immunity signaling pathways, in 37 thymuses from patients with autoimmune MG. TLR4 mRNA levels were significantly greater in thymitis (hyperplasia with diffuse B-cell infiltration) and involuted thymus than in germinal center hyperplasia and thymoma. By immunohistochemistry and confocal microscopy, cells positive for TLR4 protein were rarely detected in thymoma. However, in thymitis TLR4 protein was mostly found on epitheliomorphic (cytokeratin-positive) cells located in close association with clusters of acetylcholine receptor-positive myoid cells in thymic medulla and also at the borders between cortical and medullary areas. B cells were never TLR4-positive. TLR4 protein was also present in remnant tissue of involuted thymus. This is the first finding of a possible link between innate immunity and MG. We speculate that in a subgroup of MG patients, an exogenous or endogenous danger signal may activate the innate immune system and give rise to TLR4-mediated mechanisms contributing to autoimmunity.

• Authors: Pia Bernasconi, Massimo Barberis, Fulvio Baggi, Laura Passerini, Maria Cannone, Elisa Arnoldi, Lorenzo Novellino, Ferdinando Cornelio, Renato Mantegazza
• Journal: The American journal of pathology (Am J Pathol) Vol. 167 Issue 1 Pg. 129-39 (Jul 2005) ISSN: 0002-9440 [Print] United States
• PMID: 15972959 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Membrane Glycoproteins
• RNA, Messenger
• Receptors, Cell Surface
• TLR4 protein, human
• Toll-Like Receptor 4
• Toll-Like Receptors

Topics

• Adult
• Age of Onset
• Female
• Humans
• Immunity, Innate
• Immunohistochemistry
• Lymphatic Diseases (etiology, metabolism, pathology)
• Male
• Membrane Glycoproteins (biosynthesis)
• Microscopy, Confocal
• Myasthenia Gravis (complications, immunology, metabolism)
• RNA, Messenger (analysis)
• Receptors, Cell Surface (biosynthesis)
• Reverse Transcriptase Polymerase Chain Reaction
• Thymus Gland (immunology, metabolism, pathology)
• Toll-Like Receptor 4
• Toll-Like Receptors