Immune thrombocytopenic purpura (ITP) is an autoimmune disease in which the body increases antibody production against surface antigens on platelets, leading to platelet destruction and thrombocytopenia. The exact pathogenesis of ITP is unknown; potential causes range from inflammatory responses and reactions to single nucleotide polymorphisms that cause defective genomic changes.
The Cytokine Polymorphisms
Some disease states may cause substitution of nucleotides in the human genome, leading to an imbalance of T-helper-1 (Th1) and Th2 cells. Th1/Th2 imbalance may lead to an overproduction of inflammatory cytokines that can cause conditions such as ITP.
Tumor necrosis factor (TNF)-α is an inflammatory cytokine that upregulates the activity of phagocytes and can cause ITP. Polymorphisms such as Rs1800629 can increase the expression of this cytokine. ITP patients can overexpress TNF- α on T-cytotoxic (TCD8+) cells, which leads to secretions of perforin, granzyme, and increased apoptosis, resulting in platelet destruction. The identification and normalization of apoptotic pathways and TNF-α receptors are potential therapeutic approaches for ITP.
Activated natural killer cells, B-lymphocytes and T-lymphocytes are responsible for the production of TNF-β. The +252(G/G) polymorphism in TNF-β gene increases the concentration of TNF- β, and can contribute to the incidence of ITP and response to therapy. The presence of this polymorphism in patients infected with Helicobactor pylori may be a good prognostic factor.
Th1 cells produce another proinflammatory cytokine called interferon (IFN-ɣ), which activates macrophages and switches antibody isotypes to immunoglobulin G (IgG). The polymorphism IFN-ɣ +874A/T can lead to the AT, AA, and TT genotypes that impact levels of IFN- ɣ production. The TT genotype in particular may be more commonly seen in patients leading to a higher risk of ITP incidence. Targeting pathways that suppress the factors that negatively impact platelet production can reduce the duration of thrombocytopenia and improve platelet levels in patients with ITP.
This article originally appeared on ONA