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CVID-Associated Intestinal Disorders in the USIDNET Registry: An Analysis of Disease Manifestations, Functional Status, Comorbidities, and Treatment

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Abstract

Common variable immunodeficiency (CVID) has been subdivided into five phenotypes, including one marked by non-infectious enteropathies that lead to significant morbidity and mortality. We examined a large national registry of patients with CVID to better characterize this population and understand how the presence of enteropathy influences nutritional status, patient function, and the risk of additional non-infectious disorders in CVID patients. We also sought to illustrate the range of treatment strategies for CVID-associated enteropathies. We extracted patient data from the United States Immunodeficiency Network (USIDNET) database, which included 1415 patients with CVID, and compared those with and without intestinal disorders. Demographic and genetic profiles, functional status, and treatments targeting intestinal disorders are reported. Intestinal disorders were present in 20% of patients with CVID, including chronic diarrhea, inflammatory bowel disease, malabsorption, and others. Compared to those without enteropathies, this patient subset exhibited significantly lower Karnofsky-Lansky functional scores, greater reliance on nutritional support, higher rates of vitamin deficiencies, and increased prevalence of hematologic disorders, liver disease, pulmonary disease, granulomatous disease, and lymphoma. Genetic data were reported for only 5% of the cohort. No mutations segregated significantly to patients with or without intestinal disease. Corticosteroids were most frequently used for treatment. Patients with CVID-associated intestinal disorders exhibit higher rates of autoimmune and inflammatory comorbidities, lymphoma, malnutrition, and debility. We review recent studies implicating specific pathways underlying this immune dysregulation. Further studies are needed to evaluate the role of targeted immunomodulatory therapies for CVID-associated intestinal disorders.

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Funding

The U.S. Immunodeficiency Network (USIDNET), a program of the Immune Deficiency Foundation (IDF), is supported by a cooperative agreement, U24AI86837, from the National Institute of Allergy and Infectious Diseases (NIAID).

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  1. Department of Internal Medicine, Division of Allergy and Immunology, University of Texas Southwestern, Dallas, TX, USA

    Lauren E. Franzblau

  2. Department of Pediatrics, Division of Allergy, Immunology and Rheumatology, Columbia University Irving Medical Center, New York-Presbyterian Morgan Stanley Children’s Hospital, New York, NY, USA

    Ramsay L. Fuleihan

  3. Departments of Medicine and Pediatrics, Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Charlotte Cunningham-Rundles

  4. Departments of Internal Medicine and Pediatrics, Division of Allergy and Immunology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, F4.100B, Dallas, TX, 75390-8859, USA

    Christian A. Wysocki

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Franzblau, L.E., Fuleihan, R.L., Cunningham-Rundles, C. et al. CVID-Associated Intestinal Disorders in the USIDNET Registry: An Analysis of Disease Manifestations, Functional Status, Comorbidities, and Treatment. J Clin Immunol 44, 32 (2024). https://doi.org/10.1007/s10875-023-01604-6

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