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Published ahead of print on November 1, 2007, doi:10.1164/rccm.200701-014OC
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American Journal of Respiratory and Critical Care Medicine Vol 177. pp. 156-163, (2008)
© 2008 American Thoracic Society
doi: 10.1164/rccm.200701-014OC

Original Article

Autoantibodies in Patients with Chronic Obstructive Pulmonary Disease

Carol A. Feghali-Bostwick1,*, Aneal S. Gadgil1,*, Leo E. Otterbein2, Joseph M. Pilewski1, Michael W. Stoner1, Eva Csizmadia2, Yingze Zhang1, Frank C. Sciurba1 and Steven R. Duncan1

1 Division of Pulmonary, Allergy, and Critical Care, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; and 2 Transplant Center, Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts

Correspondence and requests for reprints should be addressed to Steven R. Duncan, M.D., Pulmonary, Allergy, and Critical Care Medicine, 628 NW MUH, 3459 Fifth Avenue, University of Pittsburgh, PA 15213. E-mail: duncsr{at}upmc.edu

Rationale: Adaptive immune responses are present in patients with chronic obstructive pulmonary disease (COPD), and it has been postulated that these processes could be autoreactive.

Objectives: To ascertain if humoral autoimmunity could play a role in COPD pathogenesis.

Methods: Circulating IgG autoantibodies were detected by immunofluorescence and immunoprecipitation. Immunohistochemistry and immunofluorescence were used to evaluate intrapulmonary IgG and complement (C3) deposition in human lung explants. Autoantibody pathogenicity was also investigated with an antibody-dependent cell-mediated cytotoxicity assay.

Measurements and Main Results: The prevalence of anti–HEp-2 epithelial cell autoantibodies in 47 smokers/former smokers with COPD (GOLD stages 1–4) was greater than among 8 subjects with a smoking history but normal spirometry and 21 healthy control subjects who had never smoked (68 vs. 13 vs. 10%, respectively; P < 0.0001). Antibodies against primary pulmonary epithelial cells were found in 12 of 12 patients with COPD versus 3 of 12 never-smoked control subjects (P < 0.001). Self-antigens immunoprecipitated from 34 of 35 (97%) of COPD plasmas (vs. 0/12 never-smoked controls). Antibodies against a particular 130-kD autoantigen (n = 7) were associated with decreased body mass index (23.2 ± 2.1 vs. 29.5 ± 1.0 kg/m2, P = 0.007). Intrapulmonary immune complexes were present in six of six and C3 was seen in five of six COPD lung explants, unlike zero of six and one of six normals, respectively. Cytotoxicity of pulmonary epithelial cells by allogeneic mononuclear cells also increased 46% after incubation with COPD plasmas (n = 10), compared with identical treatments with eight normal specimens (P = 0.03).

Conclusions: IgG autoantibodies with avidity for pulmonary epithelium, and the potential to mediate cytotoxicity, are prevalent in patients with COPD. Autoreactive adaptive immune responses may be important in the etiology of this disease.

Key Words: autoimmunity • humoral immunity • B cells • emphysema


AT A GLANCE COMMENTARY

Scientific Knowledge on the Subject
The pathologic mechanisms involved in progression of chronic obstructive pulmonary disease (COPD) remain unknown, but immunologic processes have been implicated.

What This Study Adds to the Field
IgG autoantibodies with avidity for pulmonary epithelium, and the potential to mediate cytotoxicity, are prevalent in patients with COPD. Autoreactive adaptive immune responses may be important in the etiology of this disease.

 



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