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Necrotizing enterocolitis: diagnosis with plasma IgG anti-tissue transglutaminase antibodies

Pediatric Research (2025)Cite this article

Abstract

Background

Necrotizing enterocolitis (NEC) is a severe inflammatory gastrointestinal disease in neonates. We aimed to evaluate the potential of IgG anti-tissue transglutaminase antibodies (IgG tTG) as early biomarkers for NEC.

Method

We conducted a prospective observational study, collecting plasma from 60 neonates with abdominal distension (AD), which were divided into the NEC (n = 30) and the controls (n = 30) according to the follow-up results, and used the autoantigen microarray to identify for NEC-associated autoantibodies. An Enzyme-linked immunosorbent assay (ELISA) was utilized to measure plasma IgG tTG levels in a validation study (NEC n = 43, controls n = 20).

Results

Microarray analysis indicated significantly elevated IgG tTG levels in neonates with NEC compared to controls (P < 0.001). ELISA further confirmed the significant elevation of IgG tTG in neonates with NEC (P < 0.001). IgG tTG effectively distinguished neonates with NEC from the controls, with an area under the curve (AUC) of 0.8674 (sensitivity of 72.09% and specificity of 95%). Encouragingly, IgG tTG levels were significantly higher in neonates with NEC I than in controls (P < 0.001). Additionally, as clinical conditions of neonates with NEC improved, the IgG tTG levels declined (P = 0.0159).

Conclusion

IgG tTG has potential as a biomarker for early diagnosis of NEC and predicting its prognosis after treatment.

Impact

  • Our results demonstrate that IgG anti-tissue transglutaminase antibodies possess significant diagnostic value for NEC.

  • IgG anti-tissue transglutaminase antibodies can serve as a biomarker for early diagnosis NEC and its prognosis of treatment.

  • The relationship between IgG anti-tissue transglutaminase antibodies and immune diseases may shed light on the pathogenesis of NEC, potentially opening new therapeutic avenues for preventing and treating neonates with NEC.

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Fig. 1
Fig. 2: Screening of neonate IgG autoantigen microarray and analysis of differential autoantibodies.
Fig. 3: Plasma IgG tTG can effectively diagnose NEC.
Fig. 4: Plasma IgG tTG has good diagnostic value for early NEC.

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Data availability

Data included in this manuscript are available upon request by contacting the corresponding author and will be freely available to any researcher wishing to use them for non-commercial purposes, without breaching participant confidentiality.

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Acknowledgements

The authors would like to thank Guangzhou Women and Children’s Medical Center for providing clinical samples. This study was supported by grant from the Scienceand Technology Research Project of Education Department of Jiangxi Province (Grant NO. GJJ2203559), National Natural Science Foundation of China (Grant NO. 82460317), National Natural Science Funds (Grant NO.8217060280), Natural Science Foundation of Guangdong Province (Grant NO.2114050002084), Science and Technology Program of Guangzhou (Grant NO.SL2024A03J01319, SL2024A04J00240), Jiangxi Provincial Children’s Hospital 2024 First Batch Qingmiao Scientific Research Projects (Grant NO.2024JXEYQM02), The Jiangxi Provincial Natural Science Foundation (Grant NO. 20242BAB20357), The Guangdong Basic and Applied Basic Research Foundation (Grant NO. 2024A1515013190), The Guangxi Basic and Applied Basic Research Foundation (Grant NO. 2024JJB140724) and National Natural Science Foundation of China (Grant NO. 82301955).

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Author notes

  1. These authors contributed equally: Hua Li, Chaoting Lan, Shuo Chen.

Authors and Affiliations

  1. Department of Child Healthcare, Department of Pediatric Surgery, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China

    Hua Li, Chaoting Lan, Bowen Tian, Lin Li, Yide Mu, Shenwei Huang, Jiemei Liang, Liqiong Zhu & Junjian Lv

  2. Emergency Department, the 1st affiliated hospital, Jiangxi Medical College, Nanchang University, Nanchang, China

    Shuo Chen

  3. Center for Medical Research on Innovation and Translation, Guangzhou First People’s Hospital, Guangzhou, China

    Chun Yan, Shuchen Huangfu & Yufeng Liu

  4. Department of Anesthesiology, Jiangxi Provincial Children’s Hospital, Nanchang Medical College, Nanchang, Jiangxi, China

    Yan Tian

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Contributions

Yan Tian was responsible for the writing of the article. Hua Li, Yufeng Liu, and Shuo Chen were responsible for the design of the article. Junjian Lv and Chaoting Lan reviewed the literature and collected clinical samples. Lin Li, Yide Mu, Shengwei Huang, Jiemei Liang, and Liqiong Zhu performed the experiments and collected the data. Chun Yan, Shuchen Huangfu, and Bowen Tian analyzed the data. All authors have reviewed and approved the final manuscript.

Corresponding authors

Correspondence to Junjian Lv, Yufeng Liu or Yan Tian.

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The authors declare no competing interests.

Ethics approval and consent to participate

The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was approved by the Medical Ethics Committees of Guangzhou Women and Children’s Medical Center (NO. 2018052406).

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The manuscript has been read and its submission approved by all co-authors. According to the Chinese law, the patients' kin were informed about the inclusion of their anonymized data in the database, and none declined participation.

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Li, H., Lan, C., Chen, S. et al. Necrotizing enterocolitis: diagnosis with plasma IgG anti-tissue transglutaminase antibodies. Pediatr Res (2025). https://doi.org/10.1038/s41390-025-04040-x

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