Original Article

Role of anti-tissue transglutaminase IgA antibody titer and HLA-DQ typing in the diagnosis of type 1 diabetes mellitus with celiac disease

  • Huiling HAO ,
  • Gaixiu ZHANG ,
  • Mei FENG
Expand
  • Department of Endocrinology, Shanxi Children's Hospital, Taiyuan 030013, Shanxi, China

Received date: 2023-12-05

  Online published: 2024-12-02

Abstract

Objective To investigate the predictive value of anti-tissue transglutaminase IgA (IgA-anti-tTG) antibody titers and human leukocyte antigen (HLA) -DQ typing in the occurrence of type 1 diabetes mellitus (T1DM) associated with celiac disease (CD). Methods All T1DM children<18 years old who visited the endocrinology department from November 2019 to November 2023 and healthy children who underwent physical examination during the same period were selected as the study objects. All participants underwent serological analysis and detection of CD-related HLA alleles (DQ2 and DQ8). All children with positive IgA-anti-tTG antibody underwent duodenal pathological biopsy (Marsh grade). The correlation between IgA-anti-tTG titer and Marsh classification was analyzed. ROC curve was used to evaluate the diagnostic value of IgA-anti-tTG in predicting CD. Results A total of 577 patients with T1DM were enrolled, of whom 314 (54.4%) were females with a median age of 10.0 (5.0 to 16.0) years. The control group consisted of 150 patients, including 72 females (48.0%), with a median age of 9.5 (6.0 to 17.0) years. In the T1DM group, 77 patients (13.3%) had a positive IgA-anti-tTG antibody response (>18 IU/L), of whom 60 (77.6%) had positive duodenal histopathology. Nineteen children were in Marsh 2 stage, 4 were in Marsh 3a stage, 18 were in Marsh 3b stage, 19 were in Marsh 3c stage, and all of whom were diagnosed with CD. The remaining 17 patients had negative duodenal histopathology, and after other tests, they were finally diagnosed with wheat allergy or gluten sensitivity. Duodenal pathological biopsy was also performed in 46 children in the T1DM group who were negative for IgA-anti-tTG antibody but still had glut-dependent symptoms. Among them, 21 patients were found to be Marsh stage 2 or 3 and were also diagnosed as CD. Finally, a total of 81 children were identified as having T1DM combined with CD. Spearman correlation analysis showed a significant positive correlation between IgA-anti-tTG antibody level and Marsh stage in 81 children with T1DM and CD (rs=0.76, P<0.001). The area under ROC curve (AUC) of IgA-anti-tTG antibody titers predicting CD-positive was 0.83 (95%CI: 0.72-0.93). The optimal cutoff threshold for IgA-anti-tTG antibody titer was 87.65 IU/L, and its sensitivity and specificity for predicting CD were 83.19% and 92.20%. The serum IgA-anti-tTG antibody reaction in the control group was negative. There was no significant difference in HLA-DQ typing distribution between T1DM group with CD and without CD (P>0.05). Conclusions The titer of IgA-anti-tTG antibody has a certain value in the diagnosis of T1DM children complicated with CD, and HLA typing may be an auxiliary screening method for serum antibody detection results.

Cite this article

Huiling HAO , Gaixiu ZHANG , Mei FENG . Role of anti-tissue transglutaminase IgA antibody titer and HLA-DQ typing in the diagnosis of type 1 diabetes mellitus with celiac disease[J]. Journal of Clinical Pediatrics, 2024 , 42(12) : 1025 -1031 . DOI: 10.12372/jcp.2024.23e1154

References

[1] Catassi C, Verdu EF, Bai JC, et al. Coeliac disease[J]. Lancet, 2022, 399(10344): 2413-2426.
[2] Roldán Martín MB, Márquez Romero C, Guerra Vilches E, et al. Celiac disease screening in children and adolescents with type1 diabetes mellitus: what test should be performed?[J]. Endocrinol Diabetes Nutr (Engl Ed), 2021, 68(3): 153-158.
[3] Santi E, Tascini G, Toni G, et al. Linear growth in children and adolescents with type 1 diabetes mellitus[J]. Int J Environ Res Public Health, 2019, 16(19): 3677.
[4] Husby S, Koletzko S, Korponay-Szabó I, et al. European society paediatric gastroenterology, hepatology and nutrition guidelines for diagnosing coeliac disease 2020[J]. J Pediatr Gastroenterol Nutr, 2020, 70(1): 141-156.
[5] Hujoel IA, Reilly NR, Rubio-Tapia A. Celiac disease: clinical features and diagnosis[J]. Gastroenterol Clin North Am, 2019, 48(1): 19-37.
[6] Jimenez J, Loveridge-Lenza B, Horvath K. Celiac disease in children[J]. Pediatr Clin North Am, 2021, 68(6): 1205-1219.
[7] 中华医学会儿科学分会内分泌遗传代谢学组, 中华儿科杂志编辑委员会. 中国儿童1型糖尿病标准化诊断与治疗专家共识(2020版)[J]. 中华儿科杂志, 2020, 58(6): 447-454.
[8] Horton RK, Hagen CE, Snyder MR. Pediatric celiac disease: a review of diagnostic testing and guideline recommendations[J]. J Appl Lab Med, 2022, 7(1): 294-304.
[9] Aboulaghras S, Piancatelli D, Taghzouti K, et al. Meta-analysis and systematic review of HLA DQ2/DQ8 in adults with celiac disease[J]. Int J Mol Sci, 2023, 24(2): 1188.
[10] Poddighe D, Capittini C. The role of HLA in the association between IgA deficiency and celiac disease[J]. Dis Markers, 2021, 2021: 8632861.
[11] Kurppa K, Laitinen A, Agardh D. Coeliac disease in children with type 1 diabetes[J]. Lancet Child Adolesc Health, 2018, 2(2):133-143.
[12] Zhou WY, Liu XY, Wang MM, et al. Prevalence of celiac disease in China: meta-analysis and serological survey in high-risk populations[J]. J Dig Dis, 2021, 22(11): 645-655.
[13] Joshi R, Madvariya M. Prevalence and clinical profile of celiac disease in children with type 1 diabetes mellitus[J]. Indian J Endocrinol Metab, 2015, 19(6): 797-803.
[14] Cataldo F, Lio D, Marino V, et al. IgG(1) antiendomysium and IgG antitissue transglutaminase (anti-tTG) antibodies in coeliac patients with selective IgA deficiency[J]. Gut, 2000, 47(3): 366-369.
[15] Cerqueiro Bybrant M, Udén E, Frederiksen F, et al. Celiac disease can be predicted by high levels of tissue transglutaminase antibodies in children and adolescents with type 1 diabetes[J]. Pediatr Diabetes, 2021, 22(3): 417-424.
[16] Horton RK, Hagen CE, Snyder MR. Pediatric celiac disease: a review of diagnostic testing and guideline recommendations[J]. J Appl Lab Med, 2022, 7(1): 294-304.
[17] Yl?nen V, Lindfors K, Repo M, et al. Non- biopsy serology- based diagnosis of celiac disease in adults is accurate with different commercial kits and pre-test probabilities[J]. Nutrients, 2020, 12: 2736.
[18] Al-Hussaini A, Troncone R, Khormi M, et al. Mass screening for celiac disease among school-aged children: toward exploring celiac iceberg in Saudi Arabia[J]. J Pediatr Gastroenterol Nutr, 2017, 65(6): 646-651.
[19] 李礼, 侯新琳, 姜毅. 儿童乳糜泻筛查与预后研究进展[J]. 中华实用儿科临床杂志, 2019, 34(15): 1196-1200.
[20] Husby S, Murray JA, Katzka DA. AGA clinical practice update on diagnosis and monitoring of celiac disease-changing utility of serology and histologic measures: expert review[J]. Gastroenterology, 2019, 156(4): 885-889.
Outlines

/