To understand the mechanisms responsible for homeostasis in the human immune system, IMS sought to identify novel causative genes for common variable immunodeficiency (CVID), through a collaboration with Tokyo Medical and Dental University (TMDU). CVID is the most frequent symptomatic primary immunodeficiency encountered in adults.

To this end, the collaborative teams have carried out whole exome analysis (WEA) of DNA samples obtained from five patients with CVID and their family members. After conventional WEA with HiSeq 2000, variant calling, gene annotation, and elimination of single nucleotide variants at IMS, the teams identified one to eight potential somatic changes for each patient. One of the genes identified as disease-causing was a gene that has been reported as responsible for a severe type of CVID.

The teams also identified a few candidate heterologous mutations that were each only found in a single patient or in a patient and the mother. These mutations have not been reported in the literature, and their function in the human immune system is yet to be explored. TMDU will sequence the identified candidate genes in the >200 CVID samples in their cohort, and IMS investigators are in the process of determining their functions in the immune system by using different models.