Autoimmunity-associated intronic SNP (rs2281808) detected by a simple phenotypic assay: Unique case or broader opportunity?

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2019-01, Vol.198, p.57-61
• Main Authors: Sinha, Sushmita, Renavikar, Pranav S., Crawford, Michael P., Rodgers, Jake W., Tsalikian, Eva, Tansey, Michael, Karandikar, Nitin J.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Antigens, Differentiation - genetics; Autoimmunity; Diabetes Mellitus, Type 1 - genetics; Diagnostic; Flow Cytometry; Genotype; Humans; Middle Aged; Phenotype; Polymorphism, Single Nucleotide; Receptors, Immunologic - genetics; SIRPγ; SNP rs2281808; Young Adult
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2018.12.018

Multiple genome-wide association studies have shown that the single-nucleotide polymorphism (SNP) rs2281808 TT variant, present within the signal regulatory protein gamma (SIRPG) gene, is associated with autoimmune diseases, such as type 1 diabetes. SIRPγ is the only SIRP expressed on T cells. The role of SIRPγ in human T-cells or the effect of the TT variant are poorly understood. In this short report, we demonstrate the rather unusual finding that this intronic SNP is associated with a reduction of SIRPγ expression on T cells, both in healthy subjects as well as patients with type 1 diabetes. Using this information, we propose that a simple flow cytometric detection of SIRPγ could be a potential diagnostic testing approach for the presence of SNP in the appropriate clinical context. •This is an interesting example of a phenotypic assay of protein expression tightly correlating with an intronic SNP.•A single-nucleotide polymorphism (SNP) in the SIRPG gene (rs2281808) is known to be associated with autoimmune disease.•SNP rs2281808 can be detected by a flow cytometric assay detecting the expression of the corresponding protein on T-cells.•The expression pattern may allow such detection to be utilized as a clinical diagnostic/prognostic test for rs2281808.