Humoral immunodeficiencies: conferred risk of infections and benefits of immunoglobulin replacement therapy

Abstract

Primary immune deficiency diseases (PIDDs) result from genetic defects of the immune system that increase patients’ susceptibility to infections. The types of infections that occur in PIDD patients are largely dictated by the nature of the immune deficiency, which can be defined by dysfunction of cellular or humoral defenses. An increasing number of PIDDs, including those with both cellular and humoral defects, have antibody deficiency as a major feature and can benefit from immunoglobulin replacement therapy as a result. In fact, the most common PIDDs worldwide are antibody deficiencies and include common variable immunodeficiency, congenital agammaglobulinemia, hyper IgM syndrome, specific antibody deficiency, and Good syndrome. While immunoglobulin replacement therapy is the cornerstone of treatment for the majority of these conditions, a thorough understanding of the specific infections for which these patients are at increased risk can hasten diagnosis and guide additional therapies. Moreover, the infection trends in some PIDD patients with profound defects of cellular immunity, such as autosomal dominant hyper IgE syndrome (Job’s/Buckley’s Syndrome) or dedicator of cytokinesis 8 (DOCK8) deficiency, suggest that select patients might benefit from immunoglobulin replacement therapy even if their immune deficiency is not limited to antibody defects. In this review, we provide an overview of the predisposition to infections seen in PIDDs that may benefit from immunoglobulin replacement therapy.

Intrathymic differentiation of natural antibody-producing plasma cells in human neonates

“…Mouse B1 cell-derived antibodies react to pathogen-expressed molecules, including LPS and phosphorylcholine derived from Gram-negative and Gram-positive bacteria respectively 51 . Our studies also revealed that ~ 7% of recombinant monoclonal antibodies generated from CD138 + thymic plasma cells reacted to bacteria including Gram-negative bacteria such as H. in uenzae and Gram-positive bacteria such as S. aureus, two common pathogenic bacteria infecting children with agammaglobulinemia 52 .…”

“…These antibodies are essential elements of natural immunity at birth, providing an innate line of defense against prevalent pathogens 44,55 . Children born with agammaglobulinemia or other forms of antibody de ciency invariably suffer from recurrent bacterial infections unless they receive immunoglobulin replacement therapy 52 . Despite their importance, the origin of Nabs in human neonates has remained largely unknown.…”

Assuring immune globulin potency in a world of changing pathogen challenges

“…Workshop participants identified potential candidates based on ability to cause disease in patients with PI. These were mostly respiratory pathogens, and included Streptococcus pneumoniae , Haemophilus influenzae , Moraxella catarrhalis , respiratory syncytial virus, parainfluenza, influenza, adenovirus, mycoplasma, and rhinovirus . Nonrespiratory pathogens discussed included cytomegalovirus, herpes simplex virus, enteroviruses, and meningococcus.…”

“…These were mostly respiratory pathogens, and included Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, respiratory syncytial virus, parainfluenza, influenza, adenovirus, mycoplasma, and rhinovirus. 14,28,29 Nonrespiratory pathogens discussed included cytomegalovirus, herpes simplex virus, enteroviruses, and meningococcus. Relatively limited data are available on the viral respiratory infection epidemiology of patients with PI in part because diagnostic cultures are not routinely performed.…”

Seasonal Influenza Vaccine: Uptake, Attitude, and Knowledge Among Patients Receiving Immunoglobulin Replacement Therapy

“…Patients with hypogammaglobulinemia are particularly susceptible to disease affecting the respiratory tract [ 13 ]. Regular immunoglobulin replacement therapy (IgRT), intravenous or subcutaneous, is the mainstay of management for these patients.…”