Etiopathogenesis of Basedow's disease

 

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Summary

Basedow's disease (BD) owes its name to the German physician Karl Adolph von Basedow, who described in 1840 the clinical picture of exophthalmic toxic goitre. More than one century after the seminal paper of Karl von Basedow, the ultimate cause of BD remains to be fully elucidated. In the last years, evidence was accumulated indicating that BD is a polygenic and multifactorial disease that develops as a result of a complex interplay between genetic susceptibility and environmental and endogenous factors, which leads to the loss of immune tolerance to thyroid antigens and in particular to the TSH receptor.

Our aim is to review the current knowledge on the pathogenesis of BD. To this purpose, we will firstly focus our attention on the role of genetic factors (the HLA complex, the genes encoding for thyroglobulin, the TSH receptor, CD40, CTLA-4 and PTPN22), and of environmental factors (iodine, infections, psychological stress, gender, smoking, thyroid damage, vitamin D, selenium, immune modulating agents) as possible causes of BD. Taking advantage of the experimental animal models of BD, we will then focus on the immunological mechanisms leading to the loss of tolerance in BD. The pathogenic role played by the chemokine system will be also reviewed.

Zusammenfassung

Morbus Basedow (MB) ist nach dem deutschen Arzt Karl Adolph von Basedow benannt, der 1840 das klinische Bild eines Exophthalmus mit toxischer Struma beschrieb. Über ein Jahrhundert nach dem bahnbrechenden Artikel von Karl von Basedow ist die Ursache des MB letztendlich nicht völlig geklärt. In den vergangenen Jahren haben sich Hinweise darauf ergeben, dass MB eine polygene, multifaktorielle Erkrankung ist, die als Folge eines komplexen Zusammenspiels zwischen genetisch bedingter Anfälligkeit sowie Umweltfaktoren und endogenen Faktoren entsteht, die zu einem Verlust der Immuntoleranz für Schilddrüsenantigene und insbesondere des TSH-Rezeptors führen.

Wir möchten hier den aktuellen Kenntnisstand zur Pathogenese des MB darlegen. Hierzu richten wir zunächst unser Augenmerk auf die Rolle der genetischen Faktoren (HLAKomplex, Gene, die Thyreoglobulin kodieren, TSH-Rezeptor, CD40, CTLA-4 und PTPN22) sowie die Umweltfaktoren (Iod, Infektionen, psychischer Stress, Geschlecht, Rauchen, Schilddrüsenschädigung, Vitamin D, Selen, Immunmodulatoren) als mögliche Ursachen des MB. Anhand von Tierversuchen zum MB werden wir dann vorrangig den Immun - mechanismus erläutern, der zum Toleranzverlust bei MB führt. Die pathogene Rolle des Chemokin-Systems wird ebenfalls dargestellt.

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