Granulomatous and lymphocytic interstitial lung disease: a spectrum of pulmonary histopathologic lesions in common variable immunodeficiency--histologic and immunohistochemical analyses of 16 cases

Hum Pathol. 2015 Sep;46(9):1306-14. doi: 10.1016/j.humpath.2015.05.011. Epub 2015 Jun 1.

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.

Keywords: Common variable immunodeficiency; Granuloma; Immunohistochemistry; Lymphoid interstitial lung disease; Organizing pneumonia.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Biomarkers / analysis
  • Biopsy
  • Common Variable Immunodeficiency / diagnosis*
  • Common Variable Immunodeficiency / immunology
  • Common Variable Immunodeficiency / pathology
  • Female
  • Granuloma, Respiratory Tract / diagnosis*
  • Granuloma, Respiratory Tract / immunology
  • Granuloma, Respiratory Tract / pathology
  • Humans
  • Immunohistochemistry*
  • Lung / immunology*
  • Lung / pathology*
  • Lung Diseases, Interstitial / diagnosis*
  • Lung Diseases, Interstitial / immunology
  • Lung Diseases, Interstitial / pathology
  • Lymphocyte Subsets / immunology*
  • Lymphocyte Subsets / pathology
  • Male
  • Middle Aged
  • Young Adult

Substances

  • Biomarkers