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Aberrant HS1 molecule in a patient with systemic lupus erythematosus

Genes & Immunity volume 4, pages 122–131 (2003)Cite this article

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the activation of autoreactive B lymphocytes, which are supposed to carry aberrant signal transduction after the stimulation of B-cell receptor (BCR). To investigate abnormalities in BCR-mediated signaling pathway in lupus B lymphocytes, we analyzed HS1, a molecule downstream of BCR, in 80 Japanese SLE patients. We identified 37 amino acid deletion of HS1 in a 25-year-old female patient, and the aberrant HS1 lacked a part of a functional motif. Analysis of genomic DNA revealed that the aberrant HS1 was caused by exon skipping. Family study showed that the patient as well as her father and sister are heterozygous for the abnormality. WEHI-231 cell, a mouse B cell line, transfected with the aberrant HS1 displayed a significantly increased cell death upon cross-linking of BCR. Additionally, peripheral B lymphocytes from the patient exerted increased apoptosis after BCR stimulation compared to those from control SLE patients. These data suggest that the aberrant HS1 molecule may transmit an accelerated signal after BCR stimulation and may play a role in the activation of autoreactive B lymphocytes.

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Acknowledgements

We wish to thank Dr Jun-ichi Miyazaki for providing plasmid vector, pCXN-2, and Dr Takeshi Tsubata for WEHI-231 cells.

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Authors and Affiliations

  1. Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan

    T Sawabe, T Horiuchi, H Tsukamoto, T Kojima, S Harashima, Y Kikuchi, J Otsuka, H Mitoma, S Yoshizawa & Y Niho

  2. Department of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan

    T Sawabe, R Koga & T Watanabe

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  1. T Sawabe
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Correspondence to T Horiuchi.

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Sawabe, T., Horiuchi, T., Koga, R. et al. Aberrant HS1 molecule in a patient with systemic lupus erythematosus. Genes Immun 4, 122–131 (2003). https://doi.org/10.1038/sj.gene.6363932

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