title: Tertiary lymphoid neogenesis is a component of pulmonary lymphoid hyperplasia in patients with common variable immunodeficiency.
abstract: BACKGROUND
  Despite reducing pneumonia and other infections, antibody replacement does not appear to treat pulmonary lymphoid hyperplasia (PLH) in patients with common variable immunodeficiency (CVID). The pathogenesis and optimal treatments remain to be clarified.
  
  
  OBJECTIVE
  We aimed to better understand the pathology of CVID-associated lung disease. Tertiary lymphoneogenesis, although a component of interstitial lung disease associated with autoimmune diseases, has not previously been explored in patients with CVID.
  
  
  METHODS
  We examined the clinical characteristics and pathologic findings of 6 patients with CVID with nodular/infiltrative lung disease who had biopsy specimens demonstrating PLH.
  
  
  RESULTS
  In these subjects regions of PLH contained distinct B- and T-cell zones, with B-cell predominance in 1 patient and T-cell predominance in the others. Colocalization of Ki67, Bcl6, and CD23 within this ectopic lymphoid architecture demonstrated tertiary lymphoneogenesis with active centers of cellular proliferation. One patient received rituximab with improved pulmonary radiologic findings.
  
  
  CONCLUSIONS
  Ectopic lymphoid tissue forming germinal centers suggest tertiary lymphoneogenesis in CVID-associated lung disease. B cell-targeted therapy might disrupt CVID-associated lymphoid hyperplasia.
authors.affiliation: Immunology Institute, Mount Sinai School of Medicine, New York, NY; Department of Medicine, Mount Sinai School of Medicine, New York, NY.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Maglione
authors.affiliation: Department of Pathology, Mount Sinai School of Medicine, New York, NY.
authors.forename: Huaibin M
authors.initials: HM
authors.lastname: Ko
authors.affiliation: Department of Medicine, Mount Sinai School of Medicine, New York, NY; Department of Pathology, Mount Sinai School of Medicine, New York, NY.
authors.forename: Mary B
authors.initials: MB
authors.lastname: Beasley
authors.affiliation: Department of Medicine, Mount Sinai School of Medicine, New York, NY; Department of Pathology, Mount Sinai School of Medicine, New York, NY.
authors.forename: James A
authors.initials: JA
authors.lastname: Strauchen
authors.affiliation: Immunology Institute, Mount Sinai School of Medicine, New York, NY; Department of Medicine, Mount Sinai School of Medicine, New York, NY; Department of Pediatrics, Mount Sinai School of Medicine, New York, NY. Electronic address: Charlotte.Cunningham-Rundles@mssm.edu.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Cunningham-Rundles
mesh_terms: D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D015703:Antigens, CD / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D001706:Biopsy; D017074:Common Variable Immunodeficiency / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000276:immunology; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D007136:Immunoglobulins / Q000097:blood; D007155:Immunologic Factors / Q000627:therapeutic use; D019394:Ki-67 Antigen / Q000276:immunology; D008168:Lung / Q000473:pathology; D008171:Lung Diseases / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D008232:Lymphoproliferative Disorders / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D051560:Proto-Oncogene Proteins c-bcl-6; D000069283:Rituximab; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D015703:Antigens, CD; C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; D007136:Immunoglobulins; D007155:Immunologic Factors; D019394:Ki-67 Antigen; D051560:Proto-Oncogene Proteins c-bcl-6; D000069283:Rituximab
keywords: CT; CVID; Common variable immunodeficiency; Computed tomography; Diffusing capacity of the lung for carbon monoxide; Dlco; GLILD; Granulomatous-lymphocytic interstitial lung disease; LIP; Lymphocytic interstitial pneumonia; PLH; Pulmonary lymphoid hyperplasia; chronic lung disease; ectopic follicle; germinal center; lymphoid neogenesis; pulmonary hyperplasia