Long-Term Treatment With Azathioprine Abolishes Thymic Lymphoid Follicular Hyperplasia in Myasthenia Gravis

Schalke, B.; Mertens, H. G.; Kirchner, Thomas; Wegener, S; Müller-Hermelink, H. K.

doi:10.1016/s0140-6736(87)92460-3

Cited by 9 publications

(5 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lymphofollicular hyperplasia is typically found after azathioprine treatment. 15,34 However, in our thymitis patients, time between disease onset and surgery was similar to that of the other groups and none of them had received azathioprine.…”

Section: Discussionsupporting

confidence: 63%

Increased Toll-Like Receptor 4 Expression in Thymus of Myasthenic Patients with Thymitis and Thymic Involution

Bernasconi

Barberis

Baggi

et al. 2005

The American Journal of Pathology

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 63%

Increased Toll-Like Receptor 4 Expression in Thymus of Myasthenic Patients with Thymitis and Thymic Involution

Bernasconi

Barberis

Baggi

et al. 2005

The American Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…Absence of thymitis in the residual thymus appears to support the interpretation that the small thymoma may be important for the pathogenesis of this patients MG. However, lack of thymitis in our patient may be caused by preoperative cortisone treatment, considering the report by Schalke et al [7], because immunosuppressive treatment can abolish lymphoid follicular hyperplasia.…”

Section: Discussionsupporting

confidence: 48%

Small Thymomas and Myasthenia Gravis: a Poorly Understood Association

Christiansen

Marx²,

Kiefer³

et al. 2000

Thorac cardiovasc Surg

View full text Add to dashboard Cite

Myasthenia gravis (MG) is associated with about 20% of all patients with thymomas, but the occurrence in patients with small thymomas is rare. The pathogenetic relevance of these small thymomas for MG is poorly understood until now. We report on the clinical course of a 39-year-old female patient suffering from MG and undergoing thymectomy for a small thymoma and discuss the pathogenetic importance of small thymomas for MG.

show abstract

“…It is usually interpreted as an early stage of thymitis in MG. It is also a typical finding after azathioprine treatment [88]. Morphologically, thymitis with diffuse B cell proliferation resembles lympho-follicular thymitis except for the occurrence of germinal centres in the latter.…”

Section: Thymitis With Diffuse B Cell Proliferationmentioning

confidence: 91%

Pathogenesis of myasthenia gravis

et al. 1997

View full text Add to dashboard Cite

Various studies over the last 25 years in Man and animal models have revealed many steps in the pathogenesis of myasthenia gravis (MG) which is now considered the classical organ specific, autoantibody mediated and T cell dependent human autoimmune disease. Though not a disease entity, MG is associated with pathological alterations of the thymus in about 80% of cases. These are described here with reference to distinct models of autoimmunization against the acetylcholine receptor (AChR). In MG with thymitis, intrathymic production of AChR-specific autoantibodies is the result of a classical antigen-driven immune reaction that occurs completely inside the thymus and probably involves AChR on myoid cells as the triggering (myasthenogenic) antigen. Genetic factors contribute essentially to the pathogenesis of this form of MG. In thymoma-associated MG genetic factors are probably of marginal significance. Neither intratumour autoantibody production nor T cell activation seem to occur and the AChR is not the myasthenogenic antigen. Instead, abnormal neurofilaments that share epitopes with the AChR and other autoantigen targets in paraneoplastic MG are expressed in thymomas and may trigger autoantigen-specific, non-tolerogenic T cell selection by molecular mimicry. These data support the hypothesis that initial steps in the pathogenesis of most MG cases take place within abnormal thymic microenvironments, be they inflammatory or neoplastic. Where these initial steps occur in MG cases without thymic pathology is not known. Likewise, the factors involved in the initial triggering of MG remain enigmatic in all MG subtypes.& k w d : Key words Autoimmunity · Thymus · Thymoma · Acetylcholine receptor · Aetiology& b d y :Myasthenia gravis as a prototypic model autoimmune diseaseThe triggering of a autoimmune disease is incompletely understood. In experimental models molecular alterations of autoantigens in an otherwise intact immune system may elicit autoimmunity [27], however, defects of the immune system facing an intact antigen repertoire may also lead to autoimmunity [75]. In addition, microenvironmental factors such as abnormal interleukin levels may change the interaction between a normal T cell repertoire and normal autoantigens [including the acetylcholine receptor (AChR)] as shown in mice [30,77]. In mice, the loss of an established tolerance [65,92,93] or the recruitment of ignorant T cells [32,76] have been described as mechanisms in the induction of autoimmunity but whether or not these mechanisms are involved in human autoimmune diseases has not been resolved.In fact, myasthenia gravis (MG) may be an ideal model to investigate the role of T cell tolerance in humans. The target autoantigens in MG (the AChR and striational autoantigens) are well characterized [52] as are the autoreactive T cells that play a pivotal role in MG by providing B cell help [36,61,62,82,111]. Since the late steps in the pathogenesis are well defined, MG should be an ideal disease in which to investigate those early steps in pathogenesis t...

show abstract

Long-Term Treatment With Azathioprine Abolishes Thymic Lymphoid Follicular Hyperplasia in Myasthenia Gravis

Cited by 9 publications

References 4 publications

Increased Toll-Like Receptor 4 Expression in Thymus of Myasthenic Patients with Thymitis and Thymic Involution

Increased Toll-Like Receptor 4 Expression in Thymus of Myasthenic Patients with Thymitis and Thymic Involution

Small Thymomas and Myasthenia Gravis: a Poorly Understood Association

Pathogenesis of myasthenia gravis

Contact Info

Product

Resources

About