title: Anti-ETAR and anti-AT1R autoantibodies are elevated in patients with endstage cystic fibrosis.
abstract: Autoantibodies against endothelin-1 type A receptor (ETAR) are present in systemic sclerosis complicated by lung fibrosis and pulmonary hypertension. As increased serum levels and local overproduction of endothelin-1 in the airways are reported in cystic fibrosis (CF) patients, we reasoned that anti-ETAR antibodies could be prevalent in endstage CF patients prior to lung transplantation (LTx). Also, ETAR autoantibodies are frequently associated with autoantibodies against the angiotensin II type 1 receptor (AT1R). We analyzed the presence of anti-ETAR and anti-AT1R autoantibodies in 43 LTx patients (chronic obstructive pulmonary disease (COPD), n=20; CF, n=13; interstitial lung disease (ILD), n=1). We observed overall higher anti-ETAR and anti-AT1R autoantibody titers in sera taken prior to LTx in the CF patient group as compared to COPD. No difference was found in autoantibody levels between patients with CF versus ILD. In sera taken post-LTx we found the same difference in anti-ETAR and anti-AT1R autoantibody titers between patients with CF versus COPD. No difference was found in antibody titers between sera taken prior to or 6 months after LTx. There was no association between autoantibody levels and other relevant demographic parameters, and we found no association between autoantibody titers and the development of the bronchiolitis obliterans syndrome. Both autoantibody titers were strongly correlated. We hypothesize that due to prolonged exposure to bacterial infection, increased levels of AT1R and ETAR result in a deregulated immune response causing autoantibody formation. Further research is expedient to elucidate the occurrence of autoantibodies against ETAR and AT1R and their role in disease progression.
authors.affiliation: Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: k.budding@umcutrecht.nl.
authors.forename: K
authors.initials: K
authors.lastname: Budding
authors.affiliation: Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: E A
authors.initials: EA
authors.lastname: van de Graaf
authors.affiliation: Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Hoefnagel
authors.affiliation: Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: J M
authors.initials: JM
authors.lastname: Kwakkel-van Erp
authors.affiliation: Center of Interstitial Lung Diseases, St. Antonius Hospital, Nieuwegein, The Netherlands.
authors.forename: D A
authors.initials: DA
authors.lastname: van Kessel
authors.affiliation: Department of Nephrology and Intensive Care Medicine, Medical Faculty of Charité, Berlin, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Dragun
authors.affiliation: Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Rheumatology, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Dermatology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: C E
authors.initials: CE
authors.lastname: Hack
authors.affiliation: Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: H G
authors.initials: HG
authors.lastname: Otten
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003550:Cystic Fibrosis / Q000097:blood / Q000276:immunology* / Q000601:surgery*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000097:blood / Q000276:immunology; D016040:Lung Transplantation / Q000379:methods; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D010865:Pilot Projects; D011379:Prognosis; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000276:immunology; D044140:Receptor, Angiotensin, Type 1 / Q000276:immunology / Q000378:metabolism*; D044022:Receptor, Endothelin A / Q000097:blood / Q000378:metabolism*; D012189:Retrospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D044140:Receptor, Angiotensin, Type 1; D044022:Receptor, Endothelin A
keywords: AT(1)R; Autoantibodies; Cystic fibrosis; ET(A)R; Lung transplantation