Recurrent Severe Infections and Bronchiectasis in a Heterozygous CFTR Mutation Carrier: A Case Report

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Introduction Cystic fibrosis (CF) is associated with impaired innate immune function, including dysfunction of circulating monocytes and macrophages, and is currently classified within group V inborn errors of immunity. Emerging evidence suggests that heterozygous CFTR variants may also contribute to immune dysregulation and increase susceptibility to recurrent respiratory infections and bronchiectasis. Case Presentation A previously healthy 5-year-old girl was admitted to the pediatric intensive care unit with bilateral pleuropneumonia complicated by distributive shock and multiorgan dysfunction syndrome. Streptococcal toxic shock syndrome associated with influenza A infection was diagnosed. Treatment included hemodynamic support, targeted antimicrobial therapy, invasive mechanical ventilation, renal replacement therapy, pleural drainage, and intravenous immunoglobulin (IVIG). After 39 days, she was discharged in good clinical condition. Subsequently, she developed protracted bacterial bronchitis requiring antibiotic therapy and, one year later, was readmitted with influenza B infection complicated by severe left-sided pleuropneumonia. Given her history of recurrent life-threatening respiratory infections, a comprehensive immunological and pulmonary evaluation was undertaken. Serum immunoglobulin levels, IgG subclasses, complement concentrations, and complement functional assays were within reference ranges. Lymphocyte immunophenotyping revealed a transient reduction in natural killer cell counts. Chest computed tomography demonstrated bronchiectasis of the right middle lobe. Whole-exome sequencing identified a heterozygous pathogenic CFTR variant, c.1521_1523del (p.Phe508del), while sweat chloride concentrations were within the normal range. Seasonal IVIG prophylaxis and annual influenza vaccination were initiated. No further severe infections were observed during follow-up. Conclusion This case adds to the emerging evidence that clinically relevant CFTR heterozygosity may contribute to susceptibility to recurrent severe respiratory infections and bronchiectasis. Evaluation of CFTR variants should be considered in patients with primary immunodeficiency-like respiratory phenotypes, particularly when standard immunological investigations are unrevealing. Further studies are needed to elucidate the underlying immunological mechanisms and establish evidence-based preventive strategies for this population.

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