Clinical aspects of Common Variable Immunodeficiency : There is more to the image than meets the eye

Abstract

Common variable immunodeficiency (CVID) is the most common and most diverse primary antibody deficiency. The heterogeneous group consists of patients with variable (recurrent) infections andnon-infectious complications such as autoimmunity, lymphoproliferative (granulomatous) disease, chronic lung disease, enteropathy, lymphoma and other malignancies. The largest problem for CVID patients is the development of the non-infectious complications that are associated with excess morbidity and mortality due to organ dysfunction and failure. In the current thesis we set out to identify clinical and therapeutic aspects and B- and T cell parameters that might predict which patients are prone to complications in order to improve clinical follow up and treatment of CVID patients. Our research has shown that the clinical spectrum in CVID patients is divers and that the development of infectious and non-infectious complications continues despite Ig therapy. Common complications are autoimmune, gastrointestinal disease and lymphoproliferative disease. This is probably due to the combined immune dysregulation in the B and T cell compartment in CVID patients.We have showed that the prevalence of structural airway disease (bronchiectasis) increased during follow-up despite adequate IgG trough levelsand despite the reduction of respiratory infections. Interstitial lung disease was associated with the presence of autoimmunity and distinct cellular distribution of T and B cell subpopulations. Both chronic pulmonary and gastrointestinal disease have been associated with excess morbidity and early mortality in CVID patientsTherefore, early detection and monitoring of progression of such conditions is essential. Finally, we found a considerable diagnostic delay for CVID patients, especially in those patients who were dominated by non-infectious complications. Failure to diagnose CVID and therefore delaying the start of adequate therapy for specific conditions can cause considerable morbidity. It remains important to increase awareness among doctors for the variable clinical presentations and manifestations of CVID.