Autoantibodies against islet cellantigens: Current diagnostic possibilities

Abstract

In the pathogenesis of type 1 diabetes (T1D) the causative process is the immunological destructionof pancreatic beta cells (-cells) by autoreactive cytotoxic lymphocytes and macrophages.These changes are reflected in the blood of patients as autoantibodies directed against-cell antigens. Antibodies against the following are measured: unidentified cytoplasmic -cells(ICA), glutamic acid decarboxylase (GAD), tyrosine phosphatase (IA-2), endogenous insulin (IAA)and zinc transporter 8 (ZnT8). The complete destruction of pancreatic beta cells stops the productionof autoantibodies. It is therefore believed that the determination of antibodies associatedwith T1D is of major importance in the early stages of the disease. The IAA test must beperformed prior to initiating insulin therapy. As in the case of ICA, GADA and IA-2A, a positiveIAA result in a patient who is not taking insulin confirms the presence of T1D. The latest in T1Ddiagnostics is ZnT8, an ideal complement to the current tests. About 25-30% of patients who donot have GAD, IA2A or ICA antibodies have ZnT8 antibodies. Moreover, in some clinical cases ofT1D with negative specific antibodies, the isolated presence of ICA is observed, which indicatesother, hitherto unknown antigens. Along with routine antibody measurements, optimising samplingand test development in terms of reliability and cost-effectiveness continues. This summarydescribes the present utility and future prospects for T1D prediction and diagnosis using themeasurement of autoantibodies.