alexa Single-nucleotide polymorphisms of T cell receptor zeta chain in patients with systemic lupus erythematosus.


Journal of Clinical & Cellular Immunology

Author(s): Wu J, Edberg JC, Gibson AW, Tsao B, Kimberly RP

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Abstract OBJECTIVE: Signaling molecules from the T cell receptor zeta/Fcepsilon receptor gamma (TCRzeta/FcRgamma) family play a critical role in the function of Fcgamma receptors and the TCR and are located on human chromosome 1, where lupus susceptibility genes are located. This study was undertaken to investigate the possibility of polymorphisms and/or mutations of TCRzeta in systemic lupus erythematosus (SLE). METHODS: We amplified the whole coding region of TCRzeta by reverse transcriptase-polymerase chain reaction (PCR) and directly sequenced the PCR products with a dye primer technique to facilitate heterozygote detection. RESULTS: An alternative splicing form of TCRzeta, with a CAG codon (glutamine) inserted at the splice junction of exons 4 and 5, was found both in SLE and in non-SLE subjects. Both splice isoforms of TCRzeta occurred in human mixed peripheral blood mononuclear cells, natural killer cells, and Jurkat T cells. In TCRzeta, 2 silent and 2 missense mutations were found, but neither coding change occurred in the immunoreceptor tyrosine-activation motif. No unique mutations were found in Caucasian, African American, Hispanic, Chinese, or Japanese SLE patients living in North America. CONCLUSION: The uncommon and equal occurrence of novel single-nucleotide polymorphisms in both SLE patients and normal subjects makes it improbable that they play important roles in genetic susceptibility to SLE. This article was published in Arthritis Rheum and referenced in Journal of Clinical & Cellular Immunology

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