Autoantikörper gegen Inselzellantigene und Diabetes mellitus Typ 1 unter Interferon alpha-Kombinationstherapie

Hintergrund und Fragestellung: Ziel unserer Untersuchungen war die Bestimmung von diabetesassoziierten Autoantikörpern und ihre Beziehung zur Entstehung eines Typ 1-Diabetes bei mit Interferon therapierten Patienten mit chronischer Hepatitis C.

Patienten und Methodik: Es wurden 74 Patienten (24 Frauen, 50 Männer, Durchschnittsalter: 46 Jahre) mit chronischer Hepatitis C untersucht, die auf eine vorausgegangene Interferonmonotherapie nicht angesprochen hatten. Alle erhielten eine Kombinationstherapie aus Interferon, Ribavirin und zusätzlich Amantadin 100 mg/Tag oder Plazebo über 48 Wochen. Nach Abschluss der Therapie wurden multiple Antikörper (Anti-Insulin-Antikörper, Anti-IA-2, Anti-GAD, Anti-TPO, Anti-TG, Anti-Thyreo­tropin-Rezeptorantikörper) bestimmt.

Ergebnisse: Bei zwei Patienten fanden sich am Therapieende Antikörper gegen Inselzellantigene (GAD-Autoantikörper), jedoch waren beide negativ für IA-2 und Insulin-Antikörper. Bei einem Patienten entwickelte sich 5 Monate nach Therapiebeginn ein Typ 1-Diabetes. Der Anti-GAD-Titer des Patienten war initial bei 0 IU/ml (Norm: < 1,2) gewesen, nach der Interferonmonotherapie bei 52,2 IU/ml. Während der Interferonkombinationstherapie stieg der Titer von initial 41,1 IU/ml auf 59,6 IU/ml an. Der Anti-GAD-Titer des zweiten Patienten war 0 IU/ml vor Therapie und stieg auf 1,7 IU/ml. Ein Diabetes mellitus entwickelte sich bei diesem Patienten nicht.

Folgerung: Die Ausbildung eines Diabetes mellitus ist eine seltene, jedoch schwere Komplikation einer Interferontherapie. Wiederholte Behandlungen scheinen diese Entwicklung zu begünstigen. Die Bestimmung von Autoantikörpern gegen Inselzellantigene vor einer zweiten Behandlung könnte sinnvoll sein.

Background and objective: The aim of this study was to study the appearance of autoantibodies against islet cells and the development of type 1 diabetes in patients with chronic hepatitis C during interferon treatment.

Patients and methods: 74 patients (24 women, 50 men, mean age: 46 years) with HCV infection were treated with interferon, ribavirin and amantadin versus placebo, after they had failed to previous interferon therapy in a prospective, randomised trial. At the end of treatment period anti-islet cell autoantibodies (anti-GAD, anti IA-2), anti-insulin antibodies, TSH, anti-thyroid autoantibodies (TPO, thyreoglobulin, TSH-receptor antibodies) were measured.

Results: In two patients, GAD autoantibodies were found, but both patients were negative for IA-2 and insulin antibodies. One of the patients developed type 1 diabetes five months after start of treatment. In this patient, the anti-GAD titer was initial 0 U/ml (normal: < 1.2). The titer raised to 52,2 U/ml after the interferon monotherapy. During the second interferon treatment (in combination) the titer raised from initial 41,1 U/ml to 59,6 U/ml. The anti-GAD titer of the second patient was 0 U/ml before treatment and raised to 1,7 U/ml. This patient did not develop a type 1 diabetes.

Conclusion: Type 1 diabetes is a rare but serious complication of interferon therapy. Repetitive treatment seems to facilitate this complication. Screening for islet antibodies before a second therapy could be useful.

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