Gastrointestinal Disorders Associated with Common Variable Immune Deficiency (CVID) and Chronic Granulomatous Disease (CGD)

Abstract

Common variable immune deficiency (CVID) and chronic granulomatous disease (CGD) are two of the well-characterized primary immune deficiencies with distinct pathologic defects. While CVID is predominantly a disorder of the adaptive immune system, in CGD, innate immunity is impaired. In both syndromes, the clinical manifestations include an increased susceptibility to infections and a number of non-infectious, inflammatory conditions including systemic autoimmunity, as well as organ-specific pathology. Among the organ-associated disorders, gastrointestinal (GI) manifestations are one of the most intractable. As such, non-infectious inflammatory disorders of the GI tract are clinically challenging as they have protean manifestations, often resembling inflammatory bowel disease (IBD) or celiac disease, are notoriously difficult to treat, and hence are associated with significant morbidity and mortality. Therefore, assessing the pathogenesis and defining appropriate therapeutic approaches for GI disease in patients with CVID and CGD is imperative.

Keywords: Chronic enteropathy; Chronic granulomatous disease (CGD); Common variable immune deficiency (CVID); Gastrointestinal tract; Inflammatory bowel diseases; Primary immune deficiency; Villous atrophy.

Figure 1. Pathological cases of CGD and CVID duodenal biopsies

This duodenal mucosa exhibits small aggregates of pale, lightly pigmented macrophages (white arrows) present in the lamina propria, consistent with GI lesions of CGD (x200 magnification, hematoxylin and eosin stain) (A and B). Giardia lamblia organisms are seen between red arrows on this duodenal biopsy of a CVID patient (x600, hematoxylin and eosin stain). Intraepithelial lymphocytosis of the duodenal epithelium is also present (black arrows) (C). This biopsy shows duodenal mucosa with active inflammation characterized by a prominent neutrophil infiltrate in the lamina propria. There is blunting of the villi with mild intraepithelial lymphocytosis (D, x100 and E, x200; hematoxylin and eosin stains). Immunohistochemical stain for CD138 (plasma cell marker) shows that the lamina propria is entirely devoid of plasma cells (duodenal epithelium is a positive control) (F, x100). D, E and F biopsies are from patient 2.