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Serum Iron and Ferritin Levels Are Correlated with Complement C3

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Abstract

Iron is one of the most important trace elements in the body, and its homeostasis is essential to the normal function of the immune system. Complement component C3, which is the converging of three main pathways of complement system activation, plays a key role in the innate immunity. However, the relationship between iron homeostasis and complement C3 remains unknown. The aim of our study was to analyze the relationship between serum iron and ferritin level and complement C3 and C4. A total of 590 healthy individuals were recruited in our study. Higher serum complement C3 level (p < 0.001) was found in individuals with higher serum ferritin level (> 104.0 μg/L). Moreover, serum iron level and serum ferritin level were positively correlated with complement C3 (r = 0.133, p = 0.001; r = 0.221, p < 0.001) and complement C4 (r = 0.117, p = 0.004; r = 0.123, p = 0.003). The linear regression analysis displayed that both serum iron level and serum ferritin level were linearly correlated with serum complement C3 level (adjusted beta: 2.382, 95% CI: 0.841–3.923; adjusted beta: 42.911, 95% CI: 29.070–56.751). To explore the relationship between iron homeostasis and complement C3 further, the serum samples from C3−/− mice and the wild-type (WT) control mice were obtained. Significantly lower serum iron level and higher ferritin level were found in C3−/− mice than those in WT mice (p < 0.001; p < 0.001), indicating that complement C3 might influence iron distribution and utilization. Overall, these data suggested that serum iron and ferritin levels were correlated with complement C3. The deficiency of complement C3 may disrupt the regular iron metabolism in the body.

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Acknowledgments

We thank Professor Hong Zhou for his generous support.

Funding

This study was supported by The Natural Science Foundation of the Jiangsu Higher Education Institutions of China (Grant No. 19KJB310007).

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Author notes

  1. Shuang Wen, Yeqin Sha and Yinling Li contributed equally to this work.

Authors and Affiliations

  1. Department of Immunology, Nanjing Medical University, Nanjing, 211166, Jiangsu, China

    Shuang Wen, Yeqin Sha, Yinling Li, Yuning Zhou, Fengfeng Yan, Bicheng Wang, Jingming Hu, Xu Han & Dongyan Shi

  2. Department of Laboratory Medicine, Liyang People’s Hospital, Liyang, 213300, Jiangsu, China

    Zhilian Rui

  3. Department of Pediatrics, Liyang Women and Children Health Hospital, Liyang, 213000, Jiangsu, China

    Chenhong Si

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  1. Shuang Wen
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Contributions

Dongyan Shi and Yeqin Sha contributed to the design of the project. Zhilian Rui, Yuning Zhou, Fengfeng yan, Jingming Hu, Chenhong Si, and Xu Han contributed to data collection. Yeqin Sha, Shuang Wen, and Yinling Li contributed to data analysis. Yeqin Sha and Bicheng Wang wrote the first draft of the manuscript. All authors reviewed the manuscript.

Corresponding author

Correspondence to Dongyan Shi.

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The studies were approved by the Institutional Research Board of Nanjing Medical University and were performed in accordance with the principles of the Declaration of Helsinki. All experimental protocols were approved by the Laboratory Animal Care and Use Committee at Nanjing Medical University (NJMUAC No. 053/2016).

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Wen, S., Sha, Y., Li, Y. et al. Serum Iron and Ferritin Levels Are Correlated with Complement C3. Biol Trace Elem Res 199, 2482–2488 (2021). https://doi.org/10.1007/s12011-020-02379-2

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