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Mutant CARD10 in a family with progressive immunodeficiency and autoimmunity

Cellular & Molecular Immunology volume 17, pages 782–784 (2020)Cite this article

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Autoimmunity and immunodeficiency were previously considered to be mutually exclusive conditions. However, an increased understanding of the complex immune regulatory systems and signaling mechanisms, coupled with the application of genetic analysis, has demonstrated the complex relationships between the two kinds of diseases.1 In recent years, several mild forms of primary immunodeficiencies have been discovered, presenting with opportunistic infections overlapping autoimmunity and/or allergy late in life.1

Caspase recruitment domain (CARD)-containing proteins, CARD9, CARD10 (CARMA3), CARD11 (CARMA1), and CARD14 (CARMA2), are members of the membrane-associated guanylate kinase family. These proteins function as molecular scaffolds by forming an intracellular complex with B-cell lymphoma protein 10 (BCL10) and mucosa-associated lymphoid tissue lymphoma translocation gene 1 (MALT1), which are critical for the activation of several signaling pathways, such as the nuclear factor binding near the κ light chain gene in B cells (NF-κB), c-Jun N-terminal kinase, and mammalian target of rapamycin pathways, during adaptive immunity.2,3 In addition, dominant or recessive mutations in the CARD9, CARD11, and CARD14 genes have been identified as genetic causes of immunodeficiencies in the presence/absence of autoimmune diseases and tumors in patients and families.4,5,6

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Fig. 1

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding authors on reasonable request.

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Acknowledgements

We thank all the patients and their family and the healthy volunteers for participating in the present study. We thank Long Ma, Wei-nian Shou, and Wen-jun Zhang for critical reading of the paper. This study was supported by the National Natural Science Foundation of China (81770002 to HL, 81470445 to Z-p.T., 81900002 to T.G., and 81570288 to Y-f.Y.), the Planned Science and Technology Project of Hunan Province, China (2015JC3032 to Y-f.Y.), the Science and Technology Program of Changsha, China (kq1901120 to H.L.), and the National Key Clinical Specialty Construction Projects of China.

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Author notes

  1. These authors contributed equally: Dan-hui Yang, Ting Guo

Authors and Affiliations

  1. Department of Respiratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China

    Dan-hui Yang, Ting Guo, Cheng Lei, Shui-zi Ding & Hong Luo

  2. Research Unit of Respiratory Disease, Central South University, Changsha, Hunan, 410011, China

    Dan-hui Yang, Ting Guo, Cheng Lei, Shui-zi Ding & Hong Luo

  3. Hunan Diagnosis and Treatment Center of Respiratory Disease, Changsha, Hunan, 410011, China

    Dan-hui Yang, Ting Guo, Cheng Lei, Shui-zi Ding & Hong Luo

  4. School of Life Sciences, Central South University, Changsha, Hunan, 410013, China

    Zhuang-zhuang Yuan

  5. Clinical Center for Gene Diagnosis and Therapy, Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China

    Yi-feng Yang & Zhi-ping Tan

Authors
  1. Dan-hui Yang
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  2. Ting Guo
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  6. Yi-feng Yang
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  8. Hong Luo
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Contributions

Conceived and designed the experiments: H.L. and Z-p.T. Performed the experiments: D-h.Y., T.G., and Z-z.Y., Collected samples: D-h.Y., T.G., and S-z.D. Analyzed the data: Z-p.T., H.L., D-h.Y., T.G., and Y-f.Y. Wrote the text of the main paper: D-h.Y., Z-p.T., and H.L. Prepared the figures: D-h.Y. and L.C. All authors reviewed and revised the paper.

Corresponding authors

Correspondence to Zhi-ping Tan or Hong Luo.

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Competing interests

The authors declare no competing interests.

Ethical approval

The present study was approved by the Ethics Committee of the Second Xiangya Hospital, Central South University (Changsha, China).

Informed consent

Written informed consent was obtained from the patient and his parents for publication.

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Yang, Dh., Guo, T., Yuan, Zz. et al. Mutant CARD10 in a family with progressive immunodeficiency and autoimmunity. Cell Mol Immunol 17, 782–784 (2020). https://doi.org/10.1038/s41423-020-0423-x

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