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Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by decreased immunoglobulins and recurrent infections, with non-infectious complications such as granulomatous-lymphocytic interstitial lung disease (GLILD) affecting up to 30% of patients. Using high-throughput 16S rRNA gene sequencing, salivary, sputum, and fecal microbiome from CVID patients with GLILD, comparing them to CVID patients without GLILD-with immune dysregulation (dCVID) and only infections (iCVID)-and healthy controls was analyzed. A total of 41 CVID patients, 7 with GLILD, and 15 healthy donors were included. Global fecal biodiversity was significantly lower in GLILD patients compared to CVID subgroups and controls. GLILD patients harbored different specific bacterial communities in all niches, with some keystone species common to dCVID. , , and are more frequent in the sputum of GLILD patients. Saliva in GLILD shows higher frequencies of and . Fecal samples from GLILD patients have higher levels of , , and . A non-assigned spp. is consistently associated with GLILD across different niches and could be a potential pathobiont or relevant microbiological marker for GLILD. Cluster network and correlation analyses show profound dysbiosis in the sputum, saliva, and feces of GLILD patients. These findings highlight significant microbiome alterations in CVID patients with GLILD, particularly in the respiratory tract, suggesting a possible link to both local and systemic immune dysregulation.
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http://dx.doi.org/10.3390/biomedicines12102239 | DOI Listing |
Eur J Case Rep Intern Med
July 2025
Servicio de Alergia e Inmunología, Hospital Británico de Buenos Aires, Argentina.
Introduction: Interstitial lung disease is a major complication in patients with common variable immunodeficiency. There are some publications that try to shed light on the pathophysiology of this non-infectious complication, most of them highlight the role of follicular T cells and CD21 B cells. Moreover, there are no guidelines based on randomized controlled studies on the treatment of patients with interstitial lung disease and the published case series or small uncontrolled studies describe a wide range of response rates to treatment.
View Article and Find Full Text PDFExpert Rev Respir Med
September 2025
Department of Molecular Medicine, "Sapienza" University of Rome, Rome, Italy.
Introduction: Predominantly antibody deficiencies (PADs) represent the most common inborn errors of immunity (IEIs), constituting over 50% of all IEIs detected globally. Compared to other IEIs, PADs are linked to a more favorable long-term prognosis and are typically diagnosed in adulthood. We analyzed the most recent literature on lung involvement in PAD using PUBMED Central.
View Article and Find Full Text PDFFront Immunol
May 2025
Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.
Background: Common variable immune deficiency (CVID) is the most prevalent inborn error of immunity (IEI), marked by diverse clinical-immunological phenotypes and significant immune-dysregulation, including granulomatous lymphocytic interstitial lung disease (GLILD). GLILD is a severe manifestation of CVID, contributing to reduced life expectancy and a challenging diagnosis due to its insidious and non-specific clinical course. Current management strategies for GLILD rely on expert opinion due to a lack of randomized controlled trials (RCTs).
View Article and Find Full Text PDFRespirol Case Rep
February 2025
Department of Thoracic Medicine Peninsula Health Melbourne Victoria Australia.
Granulomatous-lymphocytic interstitial lung disease (GL-ILD) is a rare pulmonary complication associated with common variable immunodeficiency (CVID), complicating diagnosis due to overlapping symptoms with other chronic respiratory conditions. This case involves a 33-year-old male with a history of sarcoidosis, presenting with recurrent sino-pulmonary infections, mediastinal and axillary lymphadenopathy, and significant splenomegaly. Despite initial treatment with prednisolone, his symptoms persisted, and FDG-PET imaging showed metabolic activity in the sinuses and lymph nodes.
View Article and Find Full Text PDFJ Allergy Clin Immunol
March 2025
Department of Medicine, DIMED, University of Padova, Padova, Italy; Internal Medicine 1, Ca' Foncello University Hospital, AULSS2, Treviso, Italy.
Background: Respiratory disease is a frequent cause of morbidity and mortality in common variable immunodeficiencies (CVIDs); however, lung function trajectories are poorly understood.
Objective: We sought to determine lung physiology measurements in CVIDs, their temporal trajectory, and their association with clinical and immunologic parameters.
Methods: This retrospective study from 5 Italian centers included patients with CVIDs who had longitudinal pulmonary function tests (PFTs) and chest computed tomography scan available.