Persistent systemic inflammation and atypical enterocolitis in patients with NEMO syndrome

Abstract

The NEMO syndrome is a primary immunodeficiency with immune and non-immune manifestations. The immune deficiency is heterogeneous showing defects in humoral, innate, and cell-mediated immunity. While the clinical aspects of the immunodeficiency are increasingly well understood, little is known about autoimmune manifestations in NEMO patients. We therefore sought to examine serologic markers of systemic inflammation and intestinal pathology in a kindred of patients with the NEMO syndrome. We observed persistent elevation of erythrocyte sedimentation rates in five patients, and two were symptomatic, with a chronic but atypical enterocolitis. Though pathologic lesions in these two patients were consistent with acute inflammation, sustained clinical improvement was only achieved with systemic and/or topical glucocorticoid therapy. Our data suggest that some patients with the NEMO syndrome exhibit persistent elevation of inflammatory markers similar to systemic autoimmune diseases and may subsequently develop an atypical enterocolitis.

Figure 1

Partial pedigree of the NEMO kindred. Symbols are as follows: open square (unaffected male), circle with black dot (carrier female), closed square (affected male). The patient numbers are depicted within the square of each affected male.

Figure 2

Persistent elevation of ESR despite an asymptomatic clinical course for patients 2-7. A) ESR levels depicted for each patient over the examined intervals. Data from each patient correspond to the following colored lines: Patient 2 (Purple), 3 (Red), 4 (Orange), 5 (Light blue), 6 (Brown), and 7 (Black). B) Control ESR levels from 2 female patients with a combined immunodeficiency (Gray line and Blue dashed line) and 2 male patients with CD40 ligand deficiency (Red line and Black dots). These patients were between 8 and 28 years of age.

Figure 3

Colonoscopy images from NEMO enterocolitis. A) Representative images from a study at Patient 3's initial presentation with abdominal symptoms, showing exudate (left frame) and mucosal inflammation (right frame). B) Two months after initiation of anti-inflammatory therapy, images were obtained from the same segment of bowel.

Figure 4

Comparison between NEMO colitis and typical colitis in IBD. A) Histopathology specimens from an IBD control. B) Histopathology from NEMO patient 3. Descriptors are noted below each image with corresponding arrows or circles.