Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency in adults; non-infectious gastrointestinal involvement may be present in up to 50% of patients, with the small intestine and colon being the most frequently affected areas. Studies have evaluated the effectiveness of biological therapy in this setting. Experience with infliximab is limited, and to the best of our knowledge, there are no published reports on the use of the subcutaneous infliximab biosimilar CT-P13. We describe the clinical, endoscopic, and histological findings of a 55-year-old man with a history of CVID-associated enteropathy involving the small intestine and colon, who has shown a satisfactory clinical, endoscopic, and histological response after three years of treatment with infliximab.

This article highlights advances in the phenotyping and management of common variable immunodeficiency (CVID). Advances in phenotyping include the use of cell-based, soluble, and genetic profiling, combined with novel applications like machine learning, to better define high-risk (complicated CVID) and low-risk (uncomplicated CVID) patient populations. Advances in management include first-in-class clinical trials to treat noninfectious disease manifestations based on convergent pathways of immune dysregulation in CVID.

Common variable immunodeficiency disease (CVID) is the most prevalent symptomatic inborn errors of immunity, determined by defective B cell function, impaired antibody production, and susceptibility to frequent respiratory infections, enteropathy, autoimmunity, and malignancy. Due to the importance of autoimmunity in CVID and the probable role of regulatory B lymphocytes, we aimed to determine the frequency of B10 cells in CVID patients with and without autoimmunity. A total of 24 CVID patients and 12 healthy controls were enrolled in the study. Patients were divided into two equal groups, with and without autoimmunity. Peripheral blood cells were stained with monoclonal antibodies (mAbs) to identify CD24hiCD38hi B cells, CD27int CD38+ (plasmablasts), and CD24hiCD27+ B cells by flow cytometry. The percentages of B10, CD24hiCD27+ and CD27int CD38+ cells were significantly lower in total CVID patients, CVID patients with autoimmunity and CVID patients without autoimmunity compared to healthy controls (mean±standard deviation (SD) percentage of B10 cells: 6.36±9.21(total CVID), 2.81±5.00 (CVID with autoimmunity), and 3.25±3.5 (CVID without autoimmunity) vs. 13.02±12.45 (healthy controls); CD24hiCD27+ cells: 2.39±3.89, 3±5.20 and 1.78±1.94 vs. 20.38±14.27; CD27int CD38+ cells: 6.80±18.49, 7.40±20.24 and 6.20±17.45 vs. 11.84±5.71). CVID patients without autoimmunity had a higher percentage of CD24hiCD38hi cells than CVID patients with autoimmunity (4.73±4.14 vs. 2.62±5.02). The defect of regulatory B cells plays a significant role in the pathogenesis of autoimmunity in CVID. Further multicenter studies with higher sample sizes are suggested to determine the role of Breg cells in the clinical course of autoimmunity.

Transient hypogammaglobulinemia of infancy (THI) is one of the most common primary antibody deficiencies presenting in early childhood and is characterized by delayed maturation of humoral immunity with spontaneous normalization of immunoglobulin G (IgG) levels in most patients. Although THI has traditionally been considered a benign, self-limited disorder, increasing evidence suggests that it represents a heterogeneous immunologic condition with variable clinical manifestations, immune abnormalities, and long-term outcomes.

The pathogenesis of pediatric Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is increasingly recognized as an immunometabolic process driven by chronic low-grade inflammation (metainflammation). While nutritional surplus and visceral adiposity are established primary drivers, the contribution of underlying subclinical host immune variations remains largely unexplored. This mini-review investigates the intersection between childhood obesity and subclinical humoral immune dysfunctions, specifically variants of Common Variable Immunodeficiency (CVID). We propose that subtle defects in adaptive immunity-such as partial secretory IgA or IgG subclass deficiencies-compromise mucosal barrier integrity, triggering a breakdown of the gut-liver axis. This barrier failure allows an influx of pathogen-associated molecular patterns (PAMPs) into the portal circulation, overwhelming hepatic immune tolerance. Within the liver, this persistent microbial exposure primes Toll-like receptor pathways and activates the NLRP3 inflammasome within Kupffer cells, accelerating hepatocyte pyroptosis and tissue damage. Concurrently, the T-cell dysregulation characteristic of CVID variants interacts with hepatic lipotoxicity, changing the disease phenotype from simple steatosis to aggressive tissue remodeling. Identifying these subclinical immunodeficiencies in progressive pediatric MASLD is essential for developing personalized, targeted immunometabolic therapies for at-risk youth.

The basal ganglia comprise a metabolically active group of nuclei implicated in refining movement and emotion. We present the case of a 52-year-old man with common variable immunodeficiency (CVID) who presented to the hospital with severe thrombocytopenia and concern for recurrent basal ganglia stroke. Three months prior, the patient presented for acute confusion and mydriasis and underwent MRI brain, revealing restricted diffusion in the right basal ganglia. Two months prior, he experienced difficulty speaking, and repeat MRI brain revealed new left basal ganglia diffusion restriction. During this admission, MRI brain was obtained again after presentation for urinary incontinence, hypophonia, and flat affect, showing bilateral basal ganglia diffusion restriction. He subsequently underwent closure of his patent foramen ovale (PFO) and had a repeat MRI brain demonstrating new enhancing lesions in the right external capsule and left lentiform nucleus. Lymph node biopsy confirmed a diagnosis of diffuse large B-cell lymphoma (DLBCL) and his basal ganglia lesions were diagnosed as secondary CNS lymphoma that was responsive to chemotherapy. In retrospect, several salient features of the presentation could have raised suspicion for an etiology other than stroke, notably the recurrence of subcortical lesions, dearth of evidence suggesting hypercoagulability of malignancy, and increased risk of lymphoma in the setting of the patient's longstanding history of CVID. Making the diagnosis of lymphoma more promptly would have enabled sooner treatment and prevented unnecessary procedures and exposure to long-term anticoagulation.

Immune effector cell (IEC) therapies using chimeric antigen receptor T cells (CAR-T) targeting B-cell maturation antigen or CD19 are FDA-approved treatments for refractory B -cell lymphoma, B-lymphoblastic leukemia, and multiple myeloma. Increasing evidence has suggested that these therapies can induce gastrointestinal injury, but the clinicopathologic spectrum and its association with clonal T-cell proliferation remain poorly defined. We retrospectively analyzed 42 GI biopsy specimens from 11 CAR-T-treated patients (8 with multiple myeloma, 2 diffuse large B-cell lymphoma, 1 acute B-lymphoblastic leukemia), comprising 4 women and 7 men (median age 68 years), with diarrhea as the predominant symptom (94%), arising at a median 4.9 months post CAR-T. Histologic evaluation, particularly of the duodenum, revealed a distinctive four-component composite histologic signature, termed a "CVID-peptic-celiac-autoimmune enteropathy-like" enteritis, characterized by plasma cell paucity (CVID-like), gastric foveolar metaplasia and Brunner gland hyperplasia (peptic duodenitis-like), intraepithelial lymphocytosis (celiac-like), and goblet cell loss with villous blunting and increased crypt epithelial apoptosis (autoimmune enteropathy-like), accompanied with atypical lamina propria lymphoid infiltrates. Those changes were most prominent in the duodenum and jejunum, less so in the ileum, and were generally mild to absent in the stomach, colon, and esophagus. Integration of histology with T-cell clonality analysis stratified the cases into two groups: the not tested/likely non-clonal group (n = 6) showed limited histologic features with isolated CVID-, peptic-, and/or autoimmune enteropathy-like changes, milder, transient symptoms, and favorable outcomes. The clonal group (n = 5) demonstrated more severe enteritis with a full composite CVID-peptic-celiac-autoimmune enteropathy-like enteritis, persistent symptoms, repeat biopsies, and higher mortality (40%). Our findings suggest a spectrum of histopathologic features of IEC-associated enteritis, characterized by a composite histologic signature that may progress to atypical lymphocytosis, often in association with clonal T-cell expansion. Recognition of this histologic pattern and incorporation of clonality testing may aid in diagnosis, risk stratification, and prognostication.