Tumor necrosis factor induced protein 3 gene polymorphism and the susceptibility to chronic primary immune thrombocytopenia in Egyptian children: a case-control study

Abstract

Background Primary immune thrombocytopenia (PIT) is an acquired auto-immune disease characterized by decreased platelet count with increased bleeding tendency. The tumor necrosis factor associated induced protein-3 (TNFAIP3) codes for the ubiquitin-modifying enzyme that is indispensable for limiting inflammation. TNFAIP3 single-nucleotide polymorphisms (SNP) has been implicated in the susceptibility to multiple auto-immune diseases. We aimed to study the distribution of TNFAIP3 (rs5029939 C>G) SNP and the possible association of the studied polymorphism with the susceptibility to chronic PIT and the response to treatment in a sample of the Egyptian pediatric chronic PIT patients. This is a case-control study performed on 40 chronic PIT patients and 50 age- and gender-matched healthy controls. DNA samples from both groups were tested for TNFAIP3 (rs5029939 C>G) SNP using polymerase chain reaction-restriction fragment length polymorphism assay. Results TNFAIP3 (rs5029939 C>G) genotype distribution showed no statistically significant difference between PIT cases and controls [CC 77.5% vs. 82.5%, and CG 22% vs. 18%, respectively; OR (95% CI), 1.323 (0.470–0.723); p, 0.596]. The minor allele frequency (MAF) of rs5029939-G was comparable between the 2 groups (0.11 vs. 0.09) [OR (95% CI), 1.282 (0.484–3.397); p, 0.617]. No statistically significant difference was observed between chronic PIT patients carrying the mutant heterozygous genotype (CG) achieving complete response and those with no response [OR (95% CI), 1.667 (0.165-16.810); p > 0.05]. The MAF of rs5029939-G was comparable between both groups [OR (95% CI), 1.571 (0.175–14.111); p > 0.05]. Conclusion This study showed no liability of patients carrying TNFAIP3 (rs5029939 C>G) polymorphism to develop chronic course of the disease or to achieve complete response to treatment. TNFAIP3 (rs5029939 C < G) SNP plays no role in either susceptibility to chronic PIT in the studied sample of Egyptian pediatric population or their response to treatment.

Upregulation of necroptosis markers RIPK3/MLKL and their crosstalk with autophagy-related protein Beclin-1 in primary immune thrombocytopenia

“…The proposed mechanism of the upregulated necroptosis markers in ITP patients is related mainly to the defective clearance of necroptotic cells and release of their contents as DAMPs that induce sterile inflammatory response and release of cytokines such as type I and type III IFNs [ 40 ] leading to cytokine imbalance which is a form of the immune cellular dysregulations participating in ITP pathogenesis [ 41 ]. High levels of TNF-α, the major trigger of necroptosis, were detected in ITP patients [ 42 , 43 ]. This indicates that necroptosis may provoke ITP through the initiation of inflammatory response and cytokines imbalance nevertheless necroptosis pathway may be triggered by the high TNF-α in ITP patients, creating a feedback loop in the progression of ITP.…”