Primary immunodeficiency

Christine Mccusker,Richard Warrington

doi:10.1186/1710-1492-7-s1-s11

Abstract

Primary immunodeficiency disorder (PID) refers to a heterogeneous group of over 130 disorders that result from defects in immune system development and/or function. PIDs are broadly classified as disorders of adaptive immunity (i.e., T-cell, B-cell or combined immunodeficiencies) or of innate immunity (e.g., phagocyte and complement disorders). Although the clinical manifestations of PIDs are highly variable, most disorders involve at least an increased susceptibility to infection. Early diagnosis and treatment are imperative for preventing significant disease-associated morbidity and, therefore, consultation with a clinical immunologist is essential. PIDs should be suspected in patients with: recurrent sinus or ear infections or pneumonias within a 1 year period; failure to thrive; poor response to prolonged use of antibiotics; persistent thrush or skin abscesses; or a family history of PID. Patients with multiple autoimmune diseases should also be evaluated. Diagnostic testing often involves lymphocyte proliferation assays, flow cytometry, measurement of serum immunoglobulin (Ig) levels, assessment of serum specific antibody titers in response to vaccine antigens, neutrophil function assays, stimulation assays for cytokine responses, and complement studies. The treatment of PIDs is complex and generally requires both supportive and definitive strategies. Ig replacement therapy is the mainstay of therapy for B-cell disorders, and is also an important supportive treatment for many patients with combined immunodeficiency disorders. The heterogeneous group of disorders involving the T-cell arm of the adaptive system, such as severe combined immunodeficiency (SCID), require immune reconstitution as soon as possible. The treatment of innate immunodeficiency disorders varies depending on the type of defect, but may involve antifungal and antibiotic prophylaxis, cytokine replacement, vaccinations and bone marrow transplantation. This article provides a detailed overview of the major categories of PIDs and strategies for the appropriate diagnosis and management of these rare disorders.

Highlights

Primary immunodeficiency disorder (PID) refers to a heterogeneous group of disorders characterized by poor or absent function in one or more components of the immune system
Less severe CIDs that do not characteristically lead to early mortality include Wiskott-Aldrich syndrome, DiGeorge syndrome, ataxia-telangiectasia, and X-linked lymphoproliferative disease
PID refers to a heterogeneous group of disorders that result from defects in immune system development and/ or function

Summary

Introduction

Primary immunodeficiency disorder (PID) refers to a heterogeneous group of disorders characterized by poor or absent function in one or more components of the immune system. Less severe CIDs that do not characteristically lead to early mortality include Wiskott-Aldrich syndrome, DiGeorge syndrome, ataxia-telangiectasia, and X-linked lymphoproliferative disease Patients with these disorders often present later in childhood with recurrent infections and clinical findings that vary depending on the specific syndrome (see Table 1). The disorder affects males and females and usually has a later age of onset than other antibody-deficiency disorders (i.e., > 10 years of age) It is associated with recurrent sinopulmonary infections, autoimmune and granulomatous disease, gastrointestinal complications and an enhanced risk of malignancy (e.g., lymphoma and gastric carcinoma). Of all the PIDs, complement deficiencies account for less than 1% of identified cases Patients with these disorders tend to present with systemic autoimmune disease that resembles lupus erythematosus or with severe or recurrent infections with encapsulated organisms (see Table 1) [3,5,8].

Frequency of hospitalizations before diagnosis

Findings

Conclusions