Jolanda Steininger, Austria
Immunology Outpatient Clinic Research DepartmentPresenter of 1 Presentation
ANALYSIS OF SOMATIC AND GERMLINE MUTATIONS OF PID GENES IN PATIENTS WITH CVID.
Abstract
Background and Aims
Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency with the majority of patients diagnosed in adulthood. So far, monogenic causes as well as risk-associated genes have been identified only in a limited number of patients. Despite tremendous efforts, for the majority of patients the genetic background is still unknown. Several studies indicate a polygenic and complex genetic background of the disease. A combination of germline and somatic mutations may play an essential role in the pathogenesis.
Methods
In this study, we have analysed next generation targeted resequencing data of 63 patients diagnosed with CVID to identify the influence of germline and somatic mutations in known PID genes on disease ontogeny and progression.
Results
We could detect a higher frequency of germline mutations in the CTLA-4 gene in patients with CVID compared to the controls, a gene which has been indicated to play a role in disease ontology in previous studies. 6 out of these 10 patients (60 %) had autoimmune manifestations including rheumatoid diseases, thrombocytopenia and inflammatory bowel disease. In addition, we found a significant reduction of global somatic mutation burden as well as potentially pathogenic somatic variants in blood leucocytes from patients with CVID. Leukocyte numbers and age at time of sequencing did not correlate with somatic mutation burden.
Conclusions
Non-infectious complications in CVID, such as autoimmune manifestations are common. We extend previous studies and confirm that germline mutations in CTLA-4 are associated with CVID.