Assessment of serological markers (interleukin-37, interleukin-40, antinuclear antibody and PA-Ab) and protein tyrosine phosphatase nonreceptor type 22 genetic profiles in children with immune thrombocytopenia: A case–control study

Abstract: BACKGROUND: Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by reduced platelet count; this condition ranges from mild symptoms to life-threatening bleeding. The protein tyrosine phosphatase nonreceptor type 22 ( PTPN22) gene codes for an enzyme called phosphatase, which controls cell signals in immune responses, specifically in T-cells. Mutations within this gene could impact the functioning of the immune system and have been considered risk factors in ITP patients. OBJECTIVES: To assess immune biomarkers (interleukin [IL]-37, IL-40, Antinuclear antibody (ANA) and PA-Ab) and PTPN22 expression and polymorphisms in children with ITP. MATERIALS AND METHODS: A case–control study was conducted involving 29 pediatric subjects with ITP and 29 healthy controls. PTPN22 expression was quantified by reverse transcription quantitative polymerase chain reaction (PCR) using the 2 −ΔΔCt method, while variants were analyzed by PCR amplification followed by Sanger sequencing. Group comparisons, receiver operating characteristic analysis, genotype and allele frequency assessment, Hardy–Weinberg equilibrium, linkage disequilibrium (LD) analysis, and correlation analysis were performed. RESULTS: Platelet count was significantly lower in ITP subjects than controls (44.31 vs. 286 × 10 3 /μL; P < 0.0001), with reductions in other hematological parameters. No significant differences were found for ANA, IL-37, IL-40, or PA-Ab. PTPN22 expression was significantly decreased in ITP subjects (0.299-fold vs. 1.0-fold; P = 0.0171) and represented moderate diagnostic value (area under the curve = 0.6813; P = 0.0177). Neither rs2488457 nor rs1395448650 was significantly associated with ITP, and LD between them was low. CONCLUSIONS: In cases of subjects with ITP, there was a marked reduction in the counts and indices of platelets and expression of the PTPN22 gene. On the other hand, other indicators, including ANA, IL-37, IL-40, PA-Ab, rs2488457, and rs1395448650, were not significantly linked to ITP.