Immunodeficiencies with hypergammaglobulinemia: a review

Abstract

Primary immunodeficiencies (PID) can present with recurrent infections, autoimmunity, inflammation, or malignancy and each of these conditions can be associated with elevated immunoglobulin. A high level of immunoglobulin G (IgG) is an uncommon finding, especially in pediatrics, and does not rule out primary immunodeficiency. Deficiencies in varied aspects of immune response have been described with high IgG. Reported PID conditions with elevated IgG include defects in humoral, cellular, and innate immunity. Some of these immunodeficiencies can have fatal outcomes, some require hematopoetic stem cell transplantation, and some require systemic medications. The mechanisms driving elevated IgG are not well understood, but in some cases abnormal cytokine production has been proposed. The evaluation of a patient with high IgG is guided by the patient's history and a physical examination, with special attention to autoimmunity in pediatrics and malignancy and liver disease in adults. In the setting of autoimmunity, chronic gastrointestinal disease, or chronic infections, the measurement of specific antibodies to evaluate the function of the IgG should be considered. An increased appreciation of elevation in IgG reflecting immune dysregulation may lead to earlier PID diagnoses.