A High Prevalence of Gastrointestinal Manifestations in Common Variable Immunodeficiency

Abstract

Objectives: Common variable immunodeficiency (CVID) is associated with a spectrum of autoimmune complications. We studied the prevalence of gastrointestinal (GI) manifestations and infections in patients with CVID.

Methods: Complete clinical data of 132 Finnish patients with CVID (106 probable and 26 possible CVID) followed up between 2007 and 2016 were collected to a structured database. Data on endoscopies, histology, and laboratory studies were retrieved from patient files.

Results: Most common referral indications were diarrhea and/or weight loss (47%-67%). Patients with probable CVID had higher fecal calprotectin and α1-antitrypsin and lower blood vitamin B12 than patients with possible CVID. Gastroscopy and colonoscopy were done to 71 (67%) and 63 (59%) patients with probable CVID, respectively. Endoscopies showed that 15% of them had chronic active gastritis and 17% atrophic gastritis and 3% had gastric adenocarcinoma. A celiac sprue-like condition was found in 7 patients (10%), of whom 3 responded to a gluten-free diet. Colonoscopies demonstrated unspecific colitis (14%), ulcerative colitis (8%), microscopic colitis (10%), and Crohn's disease (2%). Colonic polyps were noted in 30% of patients, and 3% had lower GI malignancies. Thirty-five patients with CVID had bacterial or parasitic gastroenteritis; chronic norovirus was detected in 4 patients with probable CVID. Patients with GI inflammation had higher levels of fecal calprotectin and blood CD8 T lymphocytes but lower counts of CD19CD27 memory B cells and/or CD19 B cells. Immunophenotype with low B-cell counts was associated with higher fecal calprotectin levels.

Discussion: Patients with CVID had a high prevalence of GI manifestations and infections of the GI tract. GI inflammation was associated with a distinct immunophenotype and elevated fecal calprotectin.

Figure 1.

Flowchart of patients with CVID. CVID, common variable immunodeficiency; ⁷⁵SeHCAT, selenium⁷⁵-labeled taurine salt absorption measurement for bile acid malabsorption.

Figure 2.

Fecal markers of patients with possible and probable CVID. (a) Fecal calprotectin levels in patients with probable CVID (n = 96, white bar) and in patients with possible CVID (n = 25, black bar). (b) Fecal α1-antitrypsin levels in patients with probable CVID (n = 96, white bar) and in patients with possible CVID (n = 19, black bar). Upper limits of laboratory reference ranges are marked with a dotted line: for fecal calprotectin 100 μg/g and for fecal α1-antitrypsin 268 μg/g. Results are shown for each bar (a and b) as average ± SEM. For statistical comparison between patients with possible and probable CVID, Mann-Whitney U test was used. **P < 0.0001; *P < 0.05. CVID, common variable immunodeficiency.

Figure 3.

Gastrointestinal infections in patients with CVID. Numbers of patients with GI infection and causing pathogens are shown with bars. We only show the number of patients who have had one or more infections by a pathogen, whereas the numbers of recurrent infections are not shown. Black bars mark probable CVID and white bars mark possible CVID. CVID, common variable immunodeficiency; CMV, cytomegalovirus; EAEC, enteroaggregative E. coli; EPEC, enteropathogenic E. coli; HSV, Herpes simplex virus.

Figure 4.

Inflammation of the colon, fecal markers, and immunophenotype. (a) Patients without histologic inflammation in colon biopsies (n = 50) had lower fecal calprotectin levels than patients with inflammation (n = 24). (b) Patients without histologic inflammation in the colon (n = 45) had no difference in fecal α1-antitrypsin levels compared with patients with histologic inflammation (n = 23). (c) Peripheral blood proportions of CD19⁺CD27⁺ memory B cells of CD19⁺ B cells (black bars) and CD3⁺CD8⁺ T lymphocytes of CD3⁺ T cells (white bars) in patients with or without inflammation in the colon. Histologic inflammation is indicated in the graphs with − (n = 54) and + (n = 25) signs below x axis. (d) Fecal calprotectin was higher in the subgroup of patients with a very low amount of CD19⁺ B lymphocytes (<2% of all lymphocytes; B−; n = 14) than in the rest of patients with CVID (B+; n = 107). The results are shown for each bar (a–d) as average ± SEM. For statistical comparison between patients with possible and probable CVID, Mann-Whitney U test was used. *P < 0.05.