title: Immune responses to self-antigens in asthma patients: clinical and immunopathological implications.
abstract: Asthma leads to chronic airway inflammation that shares pathological features of chronic rejection after lung transplantation. Due to the significant role of autoimmunity in chronic rejection, we hypothesized that immunity to self-antigens may also be present in asthma. The goal was to define immune responses to self-antigens in patients with asthma. Blood and clinical data were collected from 99 asthmatics and 60 controls. Serum was analyzed for antibodies (Abs) to collagen V (ColV) by enzyme-linked immunosorbent assay and correlated with disease severity. Asthmatics' sera were tested in a human protein array to determine immune responses to other self-antigens. Asthmatics had higher concentrations of Abs to ColV (predominantly immunoglobulin G isotype) compared with controls (p < 0.01). These Abs correlated with severe asthma (p < 0.01) and corticosteroid use (p = 0.032). Additionally, Abs to novel self-antigens epidermal group factor receptor (EGFr), activin A type 1 receptor, and α-catenin were detected in asthmatics. We conclude that Abs to self-antigens (ColV, EGFr, activin A type 1 receptor, and α-catenin) are present in the sera of asthmatics, correlating with clinical disease. Epithelial damage from airway inflammation during asthma may result in the exposure of cryptic self-antigens or their determinants, resulting in immune response to self-antigens, which may contribute to the pathogenesis of asthma.
authors.affiliation: Department of Surgery, Washington University, St. Louis, MO 63110, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Liu
authors.forename: Vijay
authors.initials: V
authors.lastname: Subramanian
authors.forename: Chandrika
authors.initials: C
authors.lastname: Christie
authors.forename: Mario
authors.initials: M
authors.lastname: Castro
authors.forename: Thallachallour
authors.initials: T
authors.lastname: Mohanakumar
mesh_terms: D030201:Activin Receptors, Type I / Q000097:blood / Q000276:immunology; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000627:therapeutic use; D000328:Adult; D001249:Asthma / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D001324:Autoantigens / Q000097:blood* / Q000276:immunology; D015551:Autoimmunity; D016022:Case-Control Studies; D003094:Collagen / Q000097:blood / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D066246:ErbB Receptors / Q000097:blood / Q000276:immunology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D040081:Protein Array Analysis; D012137:Respiratory System / Q000276:immunology / Q000378:metabolism; D012720:Severity of Illness Index; D051178:alpha Catenin / Q000097:blood / Q000276:immunology
chemical_list: D000305:Adrenal Cortex Hormones; D001323:Autoantibodies; D001324:Autoantigens; D051178:alpha Catenin; D003094:Collagen; D066246:ErbB Receptors; C425423:ACVR1 protein, human; D030201:Activin Receptors, Type I