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Case Reports
. 2022 Nov;42(8):1672-1684.
doi: 10.1007/s10875-022-01333-2. Epub 2022 Jul 18.

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

Lu Yang  1   2   3 , Ping Liu  4 , Hongqiang Du  1   2   3 , Ran Chen  1   2 , Bo Zhou  5 , Yanan Li  1   2   3 , Lina Zhou  1   2   3 , Xiangli Wang  4 , Cuihua Liu  4 , Yuan Ding  1   2   3 , Xuemei Tang  1   2   3 , Yongwen Chen  6 , Yunfei An  7   8   9 , Xiaodong Zhao  10   11   12   13
Affiliations
Case Reports

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

Lu Yang et al. J Clin Immunol. 2022 Nov.

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.

Keywords: Antibody deficiency; BCR signaling; CD19; CD81 deficiency; IgA nephropathy.

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References

    1. Oren R, Takahashi S, Doss C, Levy R, Levy S. TAPA-1, the target of an antiproliferative antibody, defines a new family of transmembrane proteins. Mol Cell Biol. 1990;10(8):4007–15. https://doi.org/10.1128/mcb.10.8.4007 . - DOI - PubMed - PMC
    1. Fearon DT, Carter RH. The CD19/CR2/TAPA-1 complex of B lymphocytes: linking natural to acquired immunity. Annu Rev Immunol. 1995;13:127–49. https://doi.org/10.1146/annurev.iy.13.040195.001015 . - DOI - PubMed
    1. Carter RH, Fearon DT. CD19: lowering the threshold for antigen receptor stimulation of B lymphocytes. Science. 1992;256(5053):105–7. https://doi.org/10.1126/science.1373518 . - DOI - PubMed
    1. Shoham T, Rajapaksa R, Boucheix C, Rubinstein E, Poe JC, Tedder TF, et al. The tetraspanin CD81 regulates the expression of CD19 during B cell development in a postendoplasmic reticulum compartment. J Immunol. 2003;171(8):4062–72. https://doi.org/10.4049/jimmunol.171.8.4062 . - DOI - PubMed
    1. Vences-Catalan F, Kuo CC, Sagi Y, Chen H, Kela-Madar N, van Zelm MC, et al. A mutation in the human tetraspanin CD81 gene is expressed as a truncated protein but does not enable CD19 maturation and cell surface expression. J Clin Immunol. 2015;35(3):254–63. https://doi.org/10.1007/s10875-015-0148-2 . - DOI - PubMed

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