Augmentation of the immune response to islet cell antigens with

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Z Gastroenterol 1999 Mar;37(3):235-9

[Augmentation of the immune response to islet cell

antigens with

development

of

diabetes mellitus caused by interferon-alpha therapy

in chronic

hepatitis

C].

[Article in German]

Seifarth C, Benninger J, Bohm BO, Wiest-Ladenburger U,

Hahn EG, Hensen

J

Medizinische Klinik I mit Poliklinik,

Friedrich--Universitat

Erlangen.

We report on a 36-year-old patient suffering from

chronic hepatitis C.

Because of elevated liver enzymes and histology

showing chronic

inflammation

and periportal fibrosis, interferon-alpha (IFN)

therapy was started

with a

dosage of 5 Mio units three times a week. Four months

later the patient

hat

to be hospitalized due to the typical clinical

features of a recent

onset

type 1 diabetes (BG > 300 mg/dl, HbA1c 9.6%,

ketonuria). In serum

samples

prior to and following interferon therapy, we analyzed

titers of

diabetes-related autoantibodies responding to GAD65

(glutamic acid

decarboxylase), IA2c (tyrosine phosphatase) and ICA

(islet cell

autoantibodies). While ICA were negative before

starting therapy,

IA2c-antibodies were highly elevated. In contrast.

GAD65-antibodies

were

elevated only slightly over the cut-off of the assay

before therapy

(controlled by a second different RIA assay) and

increased 100 fold

during

IFN-alpha treatment. Additionally thyroid antibodies

appeared. After

the end

of the IFN therapy, GAD65- and IA2c antibodies

remained on high levels

and

also ICA could now be found. The patient was positive

for HLA-DR4. This

case

supports the hypothesis that IFN-alpha therapy may

lead to an augmented

autoimmune reaction against islet cell antigens

resulting in the

development

of diabetes mellitus type 1, especially if there are

other predisposing

factors before IFN treatment. We further discuss the

possible

involvement of

interferon-alpha in the pathogenesis of autoimmune

diabetes with

reference

to recent studies.

PMID: 10234796, UI: 99251104

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