Abstract

BackgroundThe soluble form of CTLA-4 (sCTLA-4) is associated with several autoimmune diseases. The aim of the study is to measure the serum sCTLA-4 levels in type I diabetic (T1DM) patients and to assess the presence of autoantibodies for a possible association.MethodsOne hundred forty-two T1DM patients were enrolled in the study. Fifty of them were serologically positive for co-existing autoantibodies. One hundred and five subjects were enrolled in the study, as non-diabetic controls (1–17 years of age; median age—10 years). The serum samples of all the subjects were analyzed with ELISA to detect the concentration of sCTLA-4 and anti-GAD/IA2 IgG. Standard statistical analysis was conducted as required.ResultsNinety-four (66%) subjects of T1DM patients and five (4.7%) subjects of the non-diabetic group had antibodies positive for anti-GAD/IA2. Serum sCTLA-4 was low in most of the subjects of both the diabetic and control groups (p = 0.18). In the control group, nine individuals (8.6%) were positive for sCTLA-4. Similarly, only seven patients (4.9%) in the T1DM group had high levels of sCTLA-4, of which two were found to be double positive for anti-thyroid peroxidase and anti-thyroglobulin antibodies. In addition, among the T1DM patients, no significant relationships were observed between sCTLA-4 levels and age of onset (p = 0.43), disease duration (p = 0.09), or glycemic control (p = 0.32).ConclusionDespite the previous findings of high sCTLA-4 levels in autoimmune diseases, serum levels of sCTLA-4 are not significantly different between T1DM patients and non-diabetic adolescents. Furthermore, we did not observe any association with autoantibody presence, glycemic control, or disease duration.

Highlights

  • The soluble form of cytotoxic T lymphocyte antigen-4 (CTLA-4) is associated with several autoimmune diseases

  • Despite previous studies that reported increased soluble form of CTLA-4 (sCTLA-4) serum concentrations in autoimmune diseases, the current study reports that sCTLA-4 expression is low in Type I diabetes mellitus (T1DM) patients, with no significant difference compared to that in the non-diabetic control population

  • In conclusion, our study demonstrated that serum sCTLA-4 does not correlate with T1DM in adolescents and is not associated with the coexistence of antibodies

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Summary

Introduction

The soluble form of CTLA-4 (sCTLA-4) is associated with several autoimmune diseases. The aim of the study is to measure the serum sCTLA-4 levels in type I diabetic (T1DM) patients and to assess the presence of autoan‐ tibodies for a possible association. Type I diabetes (T1DM) is a chronic autoimmune condition characterized by progressive β-cell destruction and insufficient insulin production [1]. Similar to other autoimmune diseases, autoimmune reactivity in T1DM occurs as a result of multiple facets, including, genetic, environmental, and other aspects [2]. Despite extensive genomic studies on genetic associations, only few genes have been strongly linked with T1DM. The identified genes include cytotoxic T lymphocyte antigen-4 (CTLA-4), which might be associated with T1DM and many autoimmune diseases such as Graves’ disease, and autoimmune hypothyroidism [4]

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