title: Granulomatous and lymphocytic interstitial lung disease: a spectrum of pulmonary histopathologic lesions in common variable immunodeficiency--histologic and immunohistochemical analyses of 16 cases.
abstract: Common variable immunodeficiency is a primary immunodeficiency of unknown etiology characterized by low serum immunoglobulin G, a decreased ability to make specific antibodies, and variable T-cell defects. Approximately 10-30% of patients with common variable immunodeficiency develop clinical evidence of a diffuse parenchymal lung disease with a constellation of histopathologic findings termed granulomatous and lymphocytic interstitial lung disease. In this study, we characterized the histologic and immunohistochemical features in a series of 16 cases diagnosed by open lung biopsy. Peribronchiolar and interstitial lymphocytic infiltration, granulomatous inflammation, and organizing pneumonia were consistent features; interstitial fibrosis with architectural remodeling was also found in a subgroup of patients. By immunohistochemistry, a predominance of CD4+ T lymphocytes with variable numbers of CD8+ T cells and B cells was present, with a striking absence of FOXP3-positive T-regulatory cells. This heretofore unrecognized immunohistochemical finding needs further investigation for a potential role in the pathogenesis of the condition. The presence of interstitial fibrosis with or without architectural remodeling in a subset of patients also needs additional study, for effect on prognosis.
authors.affiliation: Department of Pathology, Medical College of Wisconsin, Milwaukee, WI 53226. Electronic address: arao@mcw.edu.
authors.forename: Nagarjun
authors.initials: N
authors.lastname: Rao
authors.affiliation: Department of Pathology, Medical College of Wisconsin, Milwaukee, WI 53226. Electronic address: amackinnon@mcw.edu.
authors.forename: A Craig
authors.initials: AC
authors.lastname: Mackinnon
authors.affiliation: Department of Pediatrics and Children's Research Institute, Medical College of Wisconsin, Milwaukee, WI 53226. Electronic address: jroutes@mcw.edu.
authors.forename: John M
authors.initials: JM
authors.lastname: Routes
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D017074:Common Variable Immunodeficiency / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D005260:Female; D015769:Granuloma, Respiratory Tract / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000276:immunology* / Q000473:pathology*; D017563:Lung Diseases, Interstitial / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D015415:Biomarkers
keywords: Common variable immunodeficiency; Granuloma; Immunohistochemistry; Lymphoid interstitial lung disease; Organizing pneumonia