Novel autoantigens immunogenic in COPD patients.
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is a respiratory inflammatory condition with autoimmune features including IgG autoantibodies. In this study we analyze the complexity of the autoantibody response and reveal the nature of the antigens that are recognized by autoantibodies in COPD patients.


METHODS
An array of 1827 gridded immunogenic peptide clones was established and screened with 17 sera of COPD patients and 60 healthy controls. Protein arrays were evaluated both by visual inspection and a recently developed computer aided image analysis technique. By this computer aided image analysis technique we computed the intensity values for each peptide clone and each serum and calculated the area under the receiver operator characteristics curve (AUC) for each clone and the separation COPD sera versus control sera.


RESULTS
By visual evaluation we detected 381 peptide clones that reacted with autoantibodies of COPD patients including 17 clones that reacted with more than 60% of the COPD sera and seven clones that reacted with more than 90% of the COPD sera. The comparison of COPD sera and controls by the automated image analysis system identified 212 peptide clones with informative AUC values. By in silico sequence analysis we found an enrichment of sequence motives previously associated with immunogenicity.


CONCLUSIONS
The identification of a rather complex humoral immune response in COPD patients supports the idea of COPD as a disease with strong autoimmune features. The identification of novel immunogenic antigens is a first step towards a better understanding of the autoimmune component of COPD.
Leidinger
Petra
P
Department of Human Genetics, Medical School, Saarland University, Building 60, 66421 Homburg/Saar, Germany. p.leidinger@mx.uni-saarland.de
Keller
Andreas
A
Heisel
Sabrina
S
Ludwig
Nicole
N
Rheinheimer
Stefanie
S
Klein
Veronika
V
Andres
Claudia
C
Hamacher
Jürg
J
Huwer
Hanno
H
Stephan
Bernhard
B
Stehle
Ingo
I
Lenhof
Hans-Peter
HP
Meese
Eckart
E
D000328:Adult; D000917:Antibody Formation; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D008297:Male; D008875:Middle Aged; D040081:Protein Array Analysis; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology*; D012372:ROC Curve; D012815:Signal Processing, Computer-Assisted
D001323:Autoantibodies; D001324:Autoantigens; D007074:Immunoglobulin G