Gastrointestinal manifestations in common variable immunodeficiency (CVID) are associated with an altered immunophenotype including B- and T-cell dysregulation

Barmettler, Sara; Ong, Mei-Sing; Farmer, Jocelyn R.; Yang, Nancy; Cobbold, Mark; Walter, Jolán E.; Long, Aidan A.; Camargo, Carlos A.

doi:10.1016/j.jaip.2019.10.024

Cited by 8 publications

(6 citation statements)

References 9 publications

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Section: Resultsmentioning

confidence: 77%

“…In keeping with previous reports, phenotyping of B-cell subpopulations has been used to demonstrate a severe reduction of switched memory B cells (CD19+ CD27+IgM-IgD-), defined as less than 2% of CD19+ cells, and expansion of CD21low B cells (more than 10% of B cells) have been associated with autoimmune or inflammatory manifestations (15,25). Although the differences were not statistically significant, a higher percentage of patients with liver disease was observed to have expanded CD21low B lymphocytes (63%) and reduced numbers of switched memory B lymphocytes (52%) when compared to patients without liver disease (35%).…”

Section: Immunologic Findingsmentioning

confidence: 79%

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Clinical manifestations and approach to the management of patients with common variable immunodeficiency and liver disease

Daza-Cajigal,

Segura-Guerrero,

López-Cueto

et al. 2023

Front. Immunol.

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PurposeThe clinical spectrum of common variable immunodeficiency (CVID) includes predisposition to infections, autoimmune/inflammatory complications and malignancy. Liver disease is developed by a proportion of patients with CVID, but limited evidence is available about its prevalence, pathogenesis and prognostic outcome. This lack of evidence leads to the absence of guidelines in clinical practice. In this study, we aimed at defining the characteristics, course and management of this CVID complication in Spain.MethodsSpanish reference centers were invited to complete a cross-sectional survey. Thirty-eight patients with CVID-related liver disease from different hospitals were evaluated by a retrospective clinical course review.ResultsIn this cohort, abnormal liver function and thrombocytopenia were found in most of the patients (95% and 79% respectively), in keeping with the higher incidence of abnormal liver imaging and splenomegaly. The most common histological findings included nodular regenerative hyperplasia (NRH) and lymphocytic infiltration, which have been associated with portal hypertension (PHTN) leading to a poorer prognosis. Autoimmune/inflammatory complications occurred in 82% of the CVID patients that developed liver disease and 52% of the patients treated with immunomodulators showed a reduction in the liver function tests’ abnormalities during treatment. Among the experts that conducted the survey, there was 80% or more consensus that the workup of CVID-related liver disease requires liver profile, abdominal ultrasound and transient elastography. The majority agreed that liver biopsy should be essential for diagnosis. There was 94% consensus that endoscopic studies should be performed in the presence of PHTN. However, there was 89% consensus that there is insufficient evidence on the management of these patients.ConclusionLiver disease varies in severity and may contribute substantially to morbidity and mortality in patients with CVID. Hence the importance of close follow-up and screening of this CVID complication to prompt early targeted intervention. Further research is needed to evaluate the pathophysiology of liver disease in patients with CVID to identify personalized treatment options. This study emphasizes the urgent need to develop international guidelines for the diagnosis and management of this CVID complication.

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Section: Resultsmentioning

confidence: 77%

Section: Immunologic Findingsmentioning

confidence: 79%

Clinical manifestations and approach to the management of patients with common variable immunodeficiency and liver disease

Daza-Cajigal,

Segura-Guerrero,

López-Cueto

et al. 2023

Front. Immunol.

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“…This is supported by the findings of intraepithelial lymphocytes, predominantly CD8 + T cells, and proinflammatory cytokines that are often identified on histology (21,22). Previous studies have also demonstrated serum immunological abnormalities, including low total B cells, low switched memory B cells, and T-cell abnormalities associated with autoimmune/inflammatory GI manifestations in CVID (23,24). This evidence of inflammatory infiltrates and immune dysregulation indicates why Ig replacement alone is typically insufficient to treat the noninfectious GI complications in these patients.…”

Section: Pathogenesis Of Cvid and Gi Manifestationsmentioning

confidence: 99%

An Expert Opinion/Approach: Clinical Presentations, Diagnostic Considerations, and Therapeutic Options for Gastrointestinal Manifestations of Common Variable Immune Deficiency

et al. 2022

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Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency. It is characterized by impaired B-cell differentiation. Although patients can be diagnosed with CVID anytime during their lifetime, most patients have symptoms for 5–9 years before their diagnosis. The diagnosis of CVID starts with a detailed history focusing on the infectious and noninfectious manifestations of the disease. In patients who are suspected to experience CVID, quantitative immunoglobulins (Ig) should be checked to confirm the diagnosis. IgG should be at least 2 times less than the age-specific SD along with either a low IgA or IgM and with evidence of impaired vaccine response. CVID is usually associated with infectious and/or noninfectious conditions, the latter of which can be inflammatory, autoimmune, lymphoproliferative, or malignant, among other manifestations. Ig therapy has positively affected the disease course of patients with infectious complications but has limited effect on the noninfectious manifestations because the noninfectious complications are related to immune dysregulation involving B cells and T cells rather than primarily due to antibody deficiency. When the gastrointestinal (GI) system is involved, patients with CVID may display signs and symptoms that mimic several GI conditions such as celiac disease, pernicious anemia, or inflammatory bowel diseases. The inflammatory bowel disease–like condition is usually treated with steroids, 5-aminosalicylates, thiopurines, or biologic agents to control the inflammation. In this review, the clinical presentations, diagnostic considerations, and therapeutic options for GI manifestations of CVID will be discussed to facilitate the individualized management of these often-complex patients.

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“…Diagnosis requires low IgG combined with low IgA/IgM, impaired vaccine response, and the exclusion of secondary causes. While individuals with CVID typically present with recurrent or atypical infections, more than 30% demonstrate non-infectious, autoinflammatory GI manifestations [20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Predominant Antibody Deficiency and Risk of Microscopic Colitis: a Nationwide Case–Control Study in Sweden

et al. 2023

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Purpose Predominant antibody deficiency (PAD) disorders, including common variable immunodeficiency (CVID), have been linked to increased risk of gastrointestinal infections and inflammatory bowel diseases. However, there are limited data on the relationship between PAD, specifically CVID, and risk of microscopic colitis (MC). Methods We performed a nationwide case–control study of Swedish adults with MC diagnosed between 1997 and 2017 (n = 13,651). Data on biopsy-verified MC were retrieved from all of Sweden’s pathology departments through the Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) study. We defined predominant antibody deficiency using International Union of Immunologic Societies (IUIS) phenotypic classification. Individuals with MC were matched to population controls by age, sex, calendar year, and county. We used logistic regression to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Results The prevalence of PAD in MC was 0.4% as compared to 0.05% in controls. After adjustment for potential confounders, this corresponded to an aOR of 7.29 (95%CI 4.64–11.63). The magnitude of the association was higher for CVID (aOR 21.01, 95% 5.48–137.44) compared to other antibody deficiencies (aOR 6.16, 95% CI 3.79–10.14). In exploratory analyses, the association between PAD and MC was particularly strong among males (aOR 31.73, 95% CI 10.82–135.04). Conclusion In this population-based study, predominant antibody deficiency was associated with increased risk of MC, particularly among males. Clinicians who encounter these patients should consider a detailed infectious history and screening for antibody deficiency.

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Gastrointestinal manifestations in common variable immunodeficiency (CVID) are associated with an altered immunophenotype including B- and T-cell dysregulation

Cited by 8 publications

References 9 publications

Clinical manifestations and approach to the management of patients with common variable immunodeficiency and liver disease

Clinical manifestations and approach to the management of patients with common variable immunodeficiency and liver disease

An Expert Opinion/Approach: Clinical Presentations, Diagnostic Considerations, and Therapeutic Options for Gastrointestinal Manifestations of Common Variable Immune Deficiency

Predominant Antibody Deficiency and Risk of Microscopic Colitis: a Nationwide Case–Control Study in Sweden

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