The Effect of Immunoglobulin Levels on CVID Enteropathy Pathogenesis and Clinical Severity
Saturday, March 5, 2016
South Exhibit Hall H (Convention Center)
Meng Chen, MD, Edith Schussler, MD, Mabel Ko, MD, Paul J. Maglione, M.D., Ph.D., Charlotte Cunningham-Rundles, M.D., Ph.D.

Mechanisms leading to enteropathy in common variable immunodeficiency (CVID) are not well understood, and treatment guidelines are yet to be defined. As immunoglobulin (Ig) replacement therapy has unclear penetrance into intestinal mucosa, we hypothesized that Ig levels noted at CVID diagnosis may impact progression of enteropathy.


We conducted a retrospective review of all patients at our institution with CVID enteropathy confirmed by intestinal biopsy showing characteristic pathology of plasma cell depletion (PCD) and/or intraepithelial lymphocytosis (IEL). We then compared Ig levels at CVID diagnosis with pathologic findings, clinical symptoms, and B cell phenotype quantification.


Fourteen CVID patients with intestinal biopsies were identified for inclusion and divided into two groups based on IgG levels: (1) IgG <200mg/dL at CVID diagnosis (n=8, IgG range 9-149 mg/dL) and (2) IgG >200 mg/dL at diagnosis (n=6, IgG range 250-393 mg/dL). Group 1 had more pathologic evidence of enteropathy as 100% of patients had PCD and 75% had IEL, versus Group 2, in which 50% had PCD and 50% had IEL. Mean weight loss in Group 1 was also greater than Group 2 (10.7 kg vs. 3.4 kg, P=0.002). Though not statistically significant, Group 1 had fewer class-switched CD27+IgM-IgD- memory B cells (2.15% vs. 5.38%, P=0.21) and lower average IgA levels than Group 2 (4.43 mg/dL vs. 14.17 mg/dL, P=0.086).


The extent of IgG deficiency at CVID diagnosis may be predictive of symptom severity and pathologic findings in CVID enteropathy. Further analysis is underway investigating the effect of Ig replacement on disease course.