Description of ICOS and ICOS-L Mutations in CVID Patients

Abstract

Common variable immunodeficiency (CVID) is a humoral immunodeficiency. Recently the discovery of genes related to the cause of CVID has been reported, among them ICOS. ICOS is a co-stimulatory molecule expressed in T cells and interacts with ICOS-L, expressed in B and antigen-presenting cells. We selected 20 CVID and 20 controls. We evaluated CD154 in T cells, surface markers in B cells (CD19, CD20, CD21, CD40, BAFF-R, CD5, CD27, IgM and IgD), PBMC cultures, and sequencing of ICOS and ICOS-L genes. All patients had low Ig levels, recurrent infections and in 30%, autoimmune manifestations. CVID patient may present higher T CD8+ counts, as well as reduced expression of CD27+ in B cells. We found, in ICOS gene, an intronic allele variant in intron 3 (nt 2729G>A), predicted as non-pathogenic, in one patient. Another non-pathogenic allelic variant (nt 11843 A>G) was found in intron 7 in two sisters, homozygous in one and heterozygous in the other. This same genetic variant was found in one patient from another family (homozygous). We found another genetic variant in intron 7 (Nt 11859C>G), not previously described and predicted as pathogenic in two patients of the same family.