The ZAP-70 (zeta-associated protein 70) deficiency is characterized by an impaired T-cell activation, which is caused by a malfunction of signal transduction.
ZAP-70 deficiency is a primary immunodeficiency disease which includes cellular immune deficiencies. Inheritance occurs as an autosomal recessive. The ZAP-70 protein plays an essential role in T-cell signaling and T cell selection in the thymus. A ZAP-70 deficiency leads to defects in T cell activation. Patients with ZAP-70 deficiency diagnosed in infancy and during early childhood, recurrent infections, similar to those in severe combined immunodeficiency (SCID); However, they live longer, and the fault may not be diagnosed until they are several years old.
The patients have normal, low or increased immunoglobulin serum levels and a normal or increased number of circulating CD4 + T cells, but essentially no CD8 T cells. Their CD4 T cells do not respond to mitogens or allogeneic cells in vitro and do not form cytotoxic T cells. In contrast, the activity of natural killer cells is normal. The diagnosis of ZAP-70 deficiency is similar to the SCID. Without hematopoietic stem cell transplantation, the disease leads to death.
How common is ZAP70
ZAP70-;inked SCID is a rare disorder. Only about 20 impact individuals have been classified. The predominance of SCID from all genetic reasons combined is approximately 1 in 50,000.
As the name indicates, this condition is triggered by mutations in the ZAP70 gene. The ZAP70 gene contributes instructions for making a protein referred to as zeta-chain-linked protein kinase. This protein is part of a signaling pathway that leads the development of and turns on (activates) immune system cells called T cells. T cells distinguish foreign substances and protect the body against infection.
The ZAP70 gene is essential for the development and function of several types of T cells. These encompass cytotoxic T cells (CD8+ T cells), whose functions include damaging cells infected by viruses. The ZAP70 gene is also implicated in the activation of helper T cells (CD4+ T cells). These cells direct and support the functions of the immune system by regulating the activities of other immune system cells.
Mutations in the ZAP70 gene inhibit the production of zeta-chain-associated protein kinase or result in a protein that is variable and cannot accomplish its function. A loss of functional zeta-chain-link protein kinase leads to the absence of CD8+ T cells and an abundance of inactive CD4+ T cells. The resulting deficit of active T cells causes people with ZAP70-related SCID to be more susceptible to infection.
This condition is inherited in an autosomal recessive pattern, which indicates both copies of the gene in every cell have mutations. The parents of an person with an autosomal recessive condition each hold one copy of the mutated gene, but they gnernerally do not show signs and symptoms of the condition.