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Expression of Humoral Autoimmunity is Related to Androgen Receptor CAG Repeat Length in Men with Systemic Lupus Erythematosus

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Abstract

We sought to explore whether inherited differences in androgen sensitivity conferred by variation in the length of a CAG repeat in exon 1 of the androgen receptor gene could be correlated with differing manifestations of humoral autoimmunity in men with lupus. In a sample of 15 men with lupus, AR CAG repeat length was linearly correlated with levels of antibodies against extractable nuclear antigens and with the number of diagnostic criteria for lupus. Protein microarrays were used to assess levels of 86 different IgG and IgM autoantibodies in the sera of these patients. IgG autoantibodies were more frequently observed in male lupus patients with longer AR CAG repeat length (>23), while IgM autoantibodies were more prevalent in subjects with shorter CAG repeat length (≤23). These data support a potential role for androgen signaling in the modulation of immunoglobulin class switching processes, with consequent impact on the autoimmune phenotype in men with lupus.

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Acknowledgments

Pilot funding for this project was awarded to AHT with WJK as mentor from NIH grant RR024982 (North Central Texas Clinical and Translational Science Initiative, Milton Packer, M.D., Principal Investigator). Fellowship support for AHT was provided by NIH training grant T32 DK007307 (WJK, Principal Investigator). The Dallas Regional Autoimmune Disease Registry is directed by David Karp, M.D., Ph.D. and supported by NIH grant P50 AR055503 (C Mohan, P.I.). We appreciate the advice and guidance of Quan Li, Ph.D., Director of the UT Southwestern Microarray Core Facility. Expert technical assistance was provided by Michelle Christadoss.

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Correspondence to William J. Kovacs.

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Tessnow, A.H., Olsen, N.J. & Kovacs, W.J. Expression of Humoral Autoimmunity is Related to Androgen Receptor CAG Repeat Length in Men with Systemic Lupus Erythematosus. J Clin Immunol 31, 567–573 (2011). https://doi.org/10.1007/s10875-011-9519-5

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