Expression of human PTPN22 alleles

Area of Science:

• Immunogenetics
• Autoimmune Diseases

Background:

• The PTPN22 Trp620 variant is associated with autoimmune disorders, which predominantly affect females.
• The mechanisms underlying this female predominance and the variant's influence on immune tolerance are complex.

Purpose of the Study:

• To investigate if allele-specific expression of the PTPN22 Arg620Trp polymorphism is influenced by cis-acting factors or sex-specific trans-acting factors, such as sex hormones.
• To determine the role of allele-specific expression in the female predominance observed in autoimmune diseases linked to PTPN22.

Main Methods:

• Utilized allele-specific transcript quantification of the PTPN22 1858T polymorphism.
• Analyzed peripheral blood mononuclear cells (PBMCs) from non-pregnant females, males, and pregnant females (first and third trimesters).
• Assessed PTPN22 expression in both non-stimulated and anti-CD3/anti-CD28 stimulated PBMCs at 48 and 72 hours.

Main Results:

• No significant difference was found in the expression of the PTPN22 1858C and 1858T alleles in non-stimulated PBMCs across all subject groups (P=0.70).
• While PTPN22 transcription increased significantly upon stimulation, the expression of both alleles increased proportionally (P=0.64).
• This indicates that allele-specific expression is not affected by cis-acting or sex-specific trans-acting factors in the studied conditions.

Conclusions:

• The study's findings exclude allele-specific expression differences as a partial explanation for the female predominance in autoimmune disorders associated with the PTPN22 Trp620 variant.
• The observed female bias in autoimmune diseases linked to PTPN22 likely stems from mechanisms other than differential allele expression.