Tissue transglutaminase autoantibodies in children with newly diagnosed type 1 diabetes are related to human leukocyte antigen but not to islet autoantibodies: A Swedish nationwide prospective population-based cohort study

Abstract

Objectives: This study explored the association between tissue transglutaminase autoantibody (tTGA), high-risk human leucocyte antigen (HLA) genotypes and islet autoantibodies in children with newly diagnosed type 1 diabetes (T1D).

Patients and methods: Dried blood spots and serum samples were taken at diagnosis from children <18 years of age participating in Better Diabetes Diagnosis (BDD), a Swedish nationwide prospective cohort study of children newly diagnosed with T1D. We analyzed tTGA, high-risk HLA DQ2 and DQ8 (DQX is neither DQ2 nor DQ8) and islet auto-antibodies (GADA, IA-2A, IAA, and three variants of Zinc transporter; ZnT8W, ZnT8R, and ZnT8QA).

Results: Out of 2705 children diagnosed with T1D, 85 (3.1%) had positive tTGA and 63 (2.3%) had borderline values. The prevalence of tTGA was higher in children with the HLA genotypes DQ2/2, DQ2/X or DQ2/8 compared to those with DQ8/8 or DQ8/X (p = .00001) and those with DQX/X (p ≤ .00001). No significant differences were found in relation to islet autoantibodies or age at diagnosis, but the presence of tTGA was more common in girls than in boys (p = .018).

Conclusion: tTGA at T1D diagnosis (both positive and borderline values 5.4%) was higher in girls and in children homozygous for DQ2/2, followed by children heterozygous for DQ2. Only children with DQ2 and/or DQ8 had tTGA. HLA typing at the diagnosis of T1D can help to identify those without risk for CD.

Keywords:

• Type 1 diabetes
• celiac disease
• tissue transglutaminase antibodies
• human leukocyte antigen
• islet autoantibodies

Acknowledgments

The authors are grateful to the children and parents who participated in the study and thank the BBD Group participants - listed in the supplementary appendix - for their excellent participation over the years. The authors also acknowledge Per Näsman, Ph.D., Senior Statistician at the Royal Institute of Technology, for his help with the statistical analysis. We would also like to pay tribute to our dear co-author Assistant Professor Lena Grahnquist, who has passed away, and dedicate this paper to her memory.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This study was supported by the Swedish Child Diabetes Foundation (Barndiabetesfonden) and Region Skåne, grants from the Sigurd and Elsa Golje Foundation, Sällskapet Baravård, Stiftelsen Samariten and HKH Kronprinsessan Lovisas Förening för Barnasjukvård.