Journal Article

Characterization of immunologic defects in patients with common variable immunodeficiency (CVID) with intestinal disease

Harpaz, Noam, Smereka, Paul, Mayer, Lloyd, Cunningham-Rundles, Charlotte, Agarwal, Shradha

2011

Overview

Common variable immunodeficiency (CVID) is a heterogeneous disorder commonly presenting with recurrent sinopulmonary infections. In all, 6%–10% of CVID patients develop an inflammatory bowel disease (IBD)-like disorder, making these patients a unique population to investigate immune-mediated gastrointestinal disease. This study examined whether defects in peripheral and/or intestinal lymphocytes are involved in disruption of the intestinal mucosa in CVID patients with inflammatory intestinal diseases.MethodsPeripheral blood (PB) T cells from healthy controls; CD or UC; CVID; and CVID with IBD were stimulated for 48 hours with anti-CD3+CD28 or phytohemagglutinin (PHA) + phorbol 12-myristate 13-acetate (PMA); cytokine production was measured by enzyme-linked immunosorbent assay (ELISA). Cytokine expression from unstimulated lamina propria lymphocytes (LPLs) was compared by real-time polymerase chain reaction (PCR). Immunohistochemistry of mucosal biopsies was performed. Cell populations were quantified by morphometry.ResultsCVID/IBD PB T cells stimulated by anti-CD3+CD28 had trends for reduced IL-2, IL-10, IFN-γ, and TNF-α compared to controls. These differences were not apparent following stimulation by PHA/PMA. Constitutive production of inflammatory cytokines by LPLs was not detected. Histologically, CVID patients had reduced/absent plasma cells with reductions in intestinal IgM and IgA. CVID patients with and without gastrointestinal (GI) disease exhibited increased CD3+ T cells, specifically CD8+, in the colon compared to normal and IBD controls, suggesting immune dysregulation.ConclusionsIntestinal inflammation in CVID patients with IBD-like disease may be mediated by abnormal cytokine production through a T-cell receptor-mediated pathway. However, the variability observed suggests multiple, rather than singular, mechanisms are involved. Histologic features such as reduced intestinal plasma cells and lack of intestinal immunoglobulins may be useful markers in diagnosing CVID in a patient with GI disease refractory to conventional therapies. (Inflamm Bowel Dis 2011;)

• Publisher: Oxford University Press,Wiley Subscription Services, Inc., A Wiley Company
• Subject: antibody deficiency / Biopsy / CD3 antigen / CD8 antigen / Colitis, Ulcerative - etiology / Colitis, Ulcerative - metabolism / Colitis, Ulcerative - pathology / Colon / Common variable immunodeficiency / Common Variable Immunodeficiency - complications / Common Variable Immunodeficiency - immunology / Common Variable Immunodeficiency - metabolism / Crohn Disease - etiology / Crohn Disease - metabolism / Crohn Disease - pathology / Cytokines / Cytokines - metabolism / Disease / Enzyme-Linked Immunosorbent Assay / Fluorescent Antibody Technique / gastrointestinal disease / Gastrointestinal tract diseases / Humans / Immune system / Immunoenzyme Techniques / Immunoglobulin A / Immunoglobulin M / Immunohistochemistry / Inflammatory bowel disease / Inflammatory bowel diseases / Interferon / Interleukin 10 / Interleukin 2 / Intestinal Diseases - etiology / Intestinal Diseases - metabolism / Intestinal Diseases - pathology / Intestine / lamina propria / Lymphocytes / Lymphocytes T / Morphometry / Mucosa / Peripheral blood / phorbol 12-myristate 13-acetate / Phorbol esters / phytohemagglutinins / Plasma cells / Polymerase chain reaction / Recurrent infection / T-Lymphocytes - immunology