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


OBJECTIVE
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.


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/m(2), 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.
Feghali-Bostwick
Carol A
CA
Division of Pulmonary, Allergy, and Critical Care, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Gadgil
Aneal S
AS
Otterbein
Leo E
LE
Pilewski
Joseph M
JM
Stoner
Michael W
MW
Csizmadia
Eva
E
Zhang
Yingze
Y
Sciurba
Frank C
FC
Duncan
Steven R
SR
D000368:Aged; D001323:Autoantibodies / Q000009:adverse effects / Q000097:blood*; D016022:Case-Control Studies; D003176:Complement C3 / Q000032:analysis; D004848:Epithelium / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007158:Immunologic Techniques; D008168:Lung / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology / Q000276:immunology*; D012907:Smoking / Q000276:immunology
D001323:Autoantibodies; D003176:Complement C3; D007074:Immunoglobulin G