CD70 Gene

The CD70 gene is a protein coding gene(CD70 protein) located on chromosome 19p13.3.

The protein encoded by the CD70 gene is a cytokine belonging to the tumor necrosis factor (TNF) ligand family. The CD70/CD27 pathway plays an important role in the development and maintenance of T cell immunity, particularly in antiviral responses.

The cytokine CD70 is a ligand for TNFRSF27/CD27, which is a surface antigen on activated but not resting T and B lymphocytes. The cytokine CD70 induces proliferation of costimulated T cells, enhances the formation of cytolytic T cells, and contributes to T cell activation. This cytokine is also thought to play a role in regulating B cell activation, natural killer cell cytotoxic function, and immunoglobulin synthesis.

Diseases associated with CD70 include:

• Lymphoproliferative syndrome type 3, a rare autosomal recessive immunodeficiency syndrome (combined immunodeficiency/CID) caused by a mutation in the CD70 gene (602840) on chromosome 19p13. Immunodeficiency is characterized by increased susceptibility of B cells to Epstein-Barr virus (EBV) infections. Ghosh S et al (2020) identified a total of 16 different mutations in CD27 and 8 in CD70, respectively, based on clinical data from 49 patients from 29 families ( CD27 , n = 33; CD70, n = 16). The majority of patients (90%) were EBV positive at diagnosis, but only about 30% had manifest infectious mononucleosis. Lymphoproliferation and lymphoma were the major clinical manifestations (70% and 43%, respectively), and 9 of the CD27-deficient patients developed hemophagocytic lymphohistiocytosis. 21 patients (43%) developed autoinflammatory features such as uveitis, arthritis, and periodic fever (Ghosh S et al. 2020).

1. Abolhassani H et al. (2017) Combined immunodeficiency and Epstein-Barr virus-induced B cell malignancy in humans with inherited CD70 deficiency. J Exp Med 214: 91-106.
2. Ghosh S et al (2020) Extended clinical and immunological phenotype and transplant outcome in CD27 and CD70 deficiency. Blood 136:2638-2655.
3. Izawa K et al (2017) Inherited CD70 deficiency in humans reveals a critical role for the CD70-CD27 pathway in immunity to Epstein-Barr virus infection. J Exp Med 214: 73-89.