RESUMO
OBJECTIVE: Iodide transport across thyrocytes constitutes a critical step for thyroid hormone biosynthesis, mediated mainly by the basolateral sodium-iodide-symporter (NIS (SLC5A5)) and the apical anion exchanger pendrin (PDS (SLC26A4)). Both transmembrane proteins have been described as autoantigens in thyroid disease, yet the reports on autoantibody (aAb) prevalence and diagnostic usefulness are conflicting. Reasons for the inconclusive findings may be small study groups and principle differences in the technologies used. DESIGN: We decided to re-evaluate this important issue by establishing novel non-radioactive tests using full-length antigens and comparable protocols, and analyzing a large cohort of thyroid patients (n = 323) and control samples (n = 400). METHODS: NIS and PDS were recombinantly expressed as fusion protein with firefly luciferase (Luc). Stably transfected HEK293 cells were used as reproducible source of the autoantigens. RESULTS: Recombinant NIS-Luc showed iodide transport activity, indicating successful expression and correct processing. Commercial antibodies yielded dose-dependent responses in the newly established assays. Reproducibility of assay signals from patient sera was verified with respect to linearity, stability and absence of matrix effects. Prevalence of PDS-aAb was similar in thyroid patients and controls (7.7% vs 5.0%). NIS-aAb were more prevalent in patients than controls (7.7% vs 1.8%), especially in Graves' Disease (12.3%). Neither NIS-aAb nor PDS-aAb concentrations were related to TPO-aAb or TSH-receptor-aAb concentrations, or to serum zinc or selenium status. CONCLUSIONS: Our data highlight a potential relevance of autoimmunity against NIS for thyroid disease, whereas an assessment of PDS-aAb in thyroid patients seems not to be of diagnostic value (yet).
Assuntos
Autoimunidade/fisiologia , Transportadores de Sulfato/sangue , Simportadores/sangue , Doenças da Glândula Tireoide/sangue , Adulto , Estudos de Coortes , Estudos Transversais , Feminino , Células HEK293 , Humanos , Masculino , Transportadores de Sulfato/imunologia , Simportadores/imunologia , Doenças da Glândula Tireoide/imunologia , Hormônios Tireóideos/sangue , Hormônios Tireóideos/imunologia , Adulto JovemRESUMO
OBJECTIVES: To define the clinical association of serum prestin autoantibodies and their impact on prognosis, as specific serum diagnostic markers in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). DESIGN: Sera from 63 patients with ISSNHL were screened prospectively for the presence of prestin autoantibodies by an enzyme-linked immunosorbent assay (Elisa) test. Serum was assayed for anti-prestin IgG antibodies using recombinant human prestin (SLC26 A5). Demographic, clinical, and audiometric variables were analyzed. RESULTS: Two patients (3.17%) had demonstrable anti-prestin antibodies in serum (exact 95% CI: -1.16% to 7.5%). No statistically significant association was found between prestin autoantibodies and demographic or audiologic parameters. CONCLUSIONS: This preliminary and novel study does not support the presence of an active humoral immune reaction against prestin in ISSNHL.
Assuntos
Autoanticorpos/sangue , Perda Auditiva Neurossensorial/imunologia , Perda Auditiva Súbita/imunologia , Imunoglobulina G/sangue , Transportadores de Sulfato/imunologia , Adolescente , Adulto , Idoso , Audiometria , Biomarcadores/sangue , Feminino , Perda Auditiva Neurossensorial/sangue , Perda Auditiva Súbita/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Adulto JovemRESUMO
OBJECTIVE: This is the first report dealing with immune-mediated inner ear disease (IMIED) hearing loss in a group of patients affected with autoimmune thyroid disease (AITD), whose treatment required corticosteroids, despite being treated with levothyroxine. Immunopathology linking the inner ear and the thyroid gland is also presented. PATIENTS: A total of 220 patients were selected with sensorineural hearing loss (SNHL) of causes other than presbycusis. Audiometry was performed and pure tone average was calculated before and after treatment with corticosteroids. RESULTS: Eighty-four (84) patients had SNHL of autoimmune origin, and 15 patients were diagnosed with AITD (Hashimoto's disease). Bilateral hearing loss was observed in 10 patients (66.5%). Sudden sensorineural hearing loss was the most frequent clinical form of presentation. Nine patients showed a hearing recovery greater than 10dB after corticosteroid treatment. CONCLUSIONS: Acquired hypothyroidism is thought to affect hearing due to different mechanisms. Although specific hormonal therapy may improve peripheral or central auditory disorders associated with hypothyroidism, the presence of IMIED in AITD patients requires another approach. Altered immune regulatory mechanisms involving Treg cells and CD4+CD45RO cells have been suggested in patients with AITD and IMIED. In the present study, although all the patients with hypothyroidism and subclinical hypothyroidism were being treated with levothyroxine, immune-mediated hearing loss was observed. Therapy with corticosteroids could achieve hearing recovery. Since inner ear and thyroid gland share possible antigen targets, we highlight the existence of IMIED in AITD patients and the importance of implementing appropriate therapy with corticosteroids.