Viral infection in primary antibody deficiency syndromes

Abstract

Patients with primary antibody deficiency syndromes such as X-linked agammaglobulinemia (XLA) and common variable immunodeficiency (CVID) are at increased risk of severe and invasive infection. Viral infection in these populations has been of increasing interest as evidence mounts that viruses contribute significant morbidity and mortality: this is mediated both directly and via aberrant immune responses. We explain the importance of the humoral immune system in defence against viral pathogens before highlighting several significant viral syndromes in patients with antibody deficiency. We explore historical cases of hepatitis C via contaminated immunoglobulin products, the predisposition to invasive enteroviral infections, prolonged excretion of vaccine-derived poliovirus, the morbidity of chronic norovirus infection, and recent literature revealing the importance of respiratory viral infections. We discuss evidence that herpesviruses may play a role in driving the inflammatory disease seen in a subset of patients. We explore the phenomenon of within-host evolution during chronic viral infection and the potential emergence of new pathogenic strains. We highlight novel and emerging viruses identified via deep sequencing techniques. We describe the treatment strategies that have been attempted in all these scenarios and the urgent outstanding questions for research.

Keywords: enterovirus; herpesvirus; immunodeficiency; norovirus; primary immune deficiency.