Increased frequencies of cochlin-specific T cells in patients with autoimmune sensorineural hearing loss.
Autoimmune sensorineural hearing loss (ASNHL) is the most common cause of sudden hearing loss in adults. Although autoimmune etiopathogenic events have long been suspected in ASNHL, inner ear-specific Ags capable of targeting T cell autoreactivity have not been identified in ASNHL. In this study, we show by ELISPOT analysis that compared with normal hearing age- and sex-matched control subjects, ASNHL patients have significantly higher frequencies of circulating T cells producing either IFN-gamma (p = 0.0001) or IL-5 (p = 0.03) in response to recombinant human cochlin, the most abundant inner ear protein. In some patients, cochlin responsiveness involved both CD4+ and CD8+ T cells whereas other patients showed cochlin responsiveness confined to CD8+ T cells. ASNHL patients also showed significantly elevated cochlin-specific serum Ab titers compared with both normal hearing age- and sex-matched control subjects and patients with noise- and/or age-related hearing loss (p < 0.05 at all dilutions tested through 1/2048). Our study is the first to show T cell responsiveness to an inner ear-specific protein in ASNHL patients, and implicates cochlin as a prominent target Ag for mediating autoimmune inner ear inflammation and hearing loss.
Baek
Moo-Jin
MJ
Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Park
Hyun-Min
HM
Johnson
Justin M
JM
Altuntas
Cengiz Z
CZ
Jane-Wit
Daniel
D
Jaini
Ritika
R
Solares
C Arturo
CA
Thomas
Dawn M
DM
Ball
Edward J
EJ
Robertson
Nahid G
NG
Morton
Cynthia C
CC
Hughes
Gordon B
GB
Tuohy
Vincent K
VK
D000368:Aged; D001327:Autoimmune Diseases / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D016326:Extracellular Matrix Proteins; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
C110668:COCH protein, human; D018984:Epitopes, T-Lymphocyte; D016326:Extracellular Matrix Proteins; D011506:Proteins; D011994:Recombinant Proteins