A Patient with Novel ICOS Mutation Presented with Progressive Loss of B Cells

Excerpt

The inducible T cell co-stimulator (ICOS) is an important co-stimulatory molecule for the T cells that belongs to the immunoglobulin superfamily of co-receptor molecules like CD28 and cytotoxic T lymphocyte–associated antigen 4 (CTLA4) [1]. ICOS plays an important role in the regulation of the T cell-mediated immune responses and it is expressed only on activated T cells, while its ligand (ICOS-L) is expressed on antigen presenting cells [2, 3]. Co-stimulation via ICOS improves helper T cell functions that is important for the differentiation and proliferation of lymphocyte subsets such as T_H1, T_H2, T_H17, T follicular helper (TFH), and regulatory T (Treg) cells [2, 4]. Moreover, ICOS mediates T and B cells’ interaction, which results in the formation of germinal centers and thus differentiates B cells into memory and long-lived plasma cells [2, 3]. The ICOS deficiency is classified as a combined immunodeficiency (CID) and encompasses broad patient phenotypes with hypogammaglobulinemia, recurrent infections, enteropathies, autoimmunity, lymphoproliferation, and malignancy [5]. …