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18.07.2022 | Original Article

Novel CD81 Mutations in a Chinese Patient Led to IgA Nephropathy and Impaired BCR Signaling

verfasst von: Lu Yang, Ping Liu, Hongqiang Du, Ran Chen, Bo Zhou, Yanan Li, Lina Zhou, Xiangli Wang, Cuihua Liu, Yuan Ding, Xuemei Tang, Yongwen Chen, Yunfei An, Xiaodong Zhao

Erschienen in: Journal of Clinical Immunology | Ausgabe 8/2022

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Abstract

Purpose

CD81 deficiency is an extremely rare primary immunodeficiency disease characterized by severe and recurrent infections, IgA-related nephropathy, and profound hypogammaglobulinemia. Only one patient has been reported so far, and the pathogenesis remains unclear. Here, we identified a new case of CD81 deficiency and described its pathogenesis.

Methods

We analyzed the clinical, genetic, and immunological features of the patient with CD81 deficiency, and explored the pathogenesis of her antibody deficiencies.

Results

The major manifestation of this patient was unexpectedly not recurrent infections but IgA nephropathy with aberrant serum galactose-deficient IgA1. Whole-exome sequencing revealed novel biallelic mutations in CD81 gene that abolished the surface expression of CD81. B cells from the patient lack membrane CD19 and showed reduced switched memory B cells and transitional B cells. Decreased expression of key molecules pY and pBTK in BCR signaling were demonstrated by confocal microscopy. RNA sequencing revealed that genes associated with BCR signaling and immunoglobulins were downregulated in CD81-deficient B cells. In addition, the patient showed increased frequency of T follicular helper cells that biased to Th1-like subsets.

Conclusion

We reported the second patient with CD81 deficiency in the world and illustrated aberrant BCR signaling in the patient, therefore helping to unravel the mechanism of antibody deficiency in CD81-deficient patients.

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Titel: Novel CD81 Mutations in a Chinese Patient Led to IgA Nephropathy and Impaired BCR Signaling
verfasst von: Lu Yang
Ping Liu
Hongqiang Du
Ran Chen
Bo Zhou
Yanan Li
Lina Zhou
Xiangli Wang
Cuihua Liu
Yuan Ding
Xuemei Tang
Yongwen Chen
Yunfei An
Xiaodong Zhao
Publikationsdatum: 18.07.2022
Verlag: Springer US
Erschienen in: Journal of Clinical Immunology / Ausgabe 8/2022
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-022-01333-2

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Novel CD81 Mutations in a Chinese Patient Led to IgA Nephropathy and Impaired BCR Signaling

Abstract

Purpose

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Conclusion

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