TY - JOUR
T1 - Characterization of immunologic defects in patients with common variable immunodeficiency (CVID) with intestinal disease
AU - Agarwal, Shradha
AU - Smereka, Paul
AU - Harpaz, Noam
AU - Cunningham-Rundles, Charlotte
AU - Mayer, Lloyd
PY - 2011/1
Y1 - 2011/1
N2 - Background: 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. Methods: Peripheral 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. Results: CVID/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. Conclusions: Intestinal 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.
AB - Background: 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. Methods: Peripheral 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. Results: CVID/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. Conclusions: Intestinal 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.
KW - antibody deficiency
KW - common variable immunodeficiency
KW - gastrointestinal disease
KW - inflammatory bowel disease
UR - http://www.scopus.com/inward/record.url?scp=78650159721&partnerID=8YFLogxK
U2 - 10.1002/ibd.21376
DO - 10.1002/ibd.21376
M3 - Article
C2 - 20629103
AN - SCOPUS:78650159721
SN - 1078-0998
VL - 17
SP - 251
EP - 259
JO - Inflammatory Bowel Diseases
JF - Inflammatory Bowel Diseases
IS - 1
ER -