Role of humoral beta‐cell autoimmunity in type 1 diabetes

Islet cell antibodies (ICA) were found for the first time more than 40 yr ago in patients with autoimmune endocrine deficiencies, including type 1 diabetes (T1D). ICA detected by indirect immunofluorescence represent a heterogeneous group of autoantibodies targeting a series of biochemical autoantigens, such as the protein tyrosine phosphatase related islet antigen 2 (IA‐2), the 65 kD isoform of glutamic acid decarboxylase (GA65), and zinc transporter 8 (ZnT8) as well as currently unidentified autoantigens. The general view is that the diabetes‐associated autoantibodies are not directly involved in beta‐cell destruction but function as biomarkers of an ongoing destructive process. The diabetes‐associated autoantibodies remain the strongest predictive marker for future development of T1D. Positivity for multiple (≥2) autoantibodies is highly predictive of clinical disease both among first‐degree relatives and in the general population. Autoantibody titers are highly variable during the preclinical phase, but in many cases the titers tend to decrease before diagnosis. The first signs of beta‐cell autoimmunity may appear early during the first months of life. The majority of those individuals diagnosed with T1D before puberty seroconvert to autoantibody positivity before the age of 3 yr. The natural course and duration of preclinical diabetes vary substantially from one individual to another. The characteristics of the isotype‐specific response during preclinic...
Source: Pediatric Diabetes - Category: Endocrinology Authors: Tags: Review Article Source Type: research