Showing papers by "Francesco Latrofa published in 2003"

Disappearance of humoral thyroid autoimmunity after complete removal of thyroid antigens.

Abstract: Le malattie autoimmuni della tiroide sono caratterizzate dalla presenza di anticorpi diretti contro la tireoperossidasi (TPO), la tireoglobulina (Tg) e il recettore per l’ormone tireotropo (TSH-R). Questo studio ha valutato se la rimozione completa degli antigeni tiroidei fosse in grado di indurre la scomparsa dei segni di autoimmunita tiroidea circolante. Lo studio e basato su una revisione retrospettiva delle cartelle cliniche di pazienti che erano stati seguiti e trattati secondo un protocollo standard. Sono stati studiati 182 pazienti affetti da tumore differenziato della tiroide i quali, per la coesistenza di una tiroidite cronica autoimmune, di un morbo di Basedow o di una tiroidite focale autoimmune, risultavano positivi per anticorpi anti-TPO (TPOAb), anti-Tg (TgAb) o anti-TSH-R (TRAb). Dei 182 soggetti, 151 erano di sesso femminile e 31 di sesso maschile; l’eta media era di 39,7±13,7 anni, con un range da 6 a 81 anni. Tutti i pazienti sono stati sottoposti a tiroidectomia totale e a trattamento con iodio radioattivo allo scopo di ablare il tessuto tiroideo residuo o metastatico. Il follow-up e stato effettuato mediante scintigrafie corporee totali con radioiodio e dosaggio della Tg circolante. La media del follow-up era di 10,1±4,1 anni, con un range di 4–20 anni. A seguito del trattamento con tiroidectomia totale e iodio radioattivo, si e verificata la scomparsa dei TgAb, TPOAb e TRAb. La mediana di scomparsa e stata di 6,3 anni per iTPOAb e di 3,0 anni per i TgAb. La scomparsa del tessuto tiroideo e quella degli anticorpi antitiroide erano correlate in modo statisticamente significativo. La persistenza di TPOAb e TgAb non veniva influenzata dal sesso, dall’eta e dalla concomitanza della tiroidite autoimmune o del morbo di Basedow.

The thyrotropin receptor autoantigen in Graves disease is the culprit as well as the victim

Abstract: Graves disease, a common organ-specific autoimmune disease affecting humans, differs from all other autoimmune diseases in being associated with target organ hyperfunction rather than organ damage. Clinical thyrotoxicosis is directly caused by autoantibodies that activate the thyrotropin receptor (TSHR). The etiology of Graves disease is multifactorial, with nongenetic factors playing an important role. Of the latter, there is the intriguing possibility that the molecular structure of the target antigen contributes to the development of thyroid-stimulatory autoantibodies (TSAb's). Among the glycoprotein hormone receptors, only the TSHR undergoes intramolecular cleavage into disulfide-linked subunits with consequent shedding of some of the extracellular, autoantibody-binding A subunits. Functional autoantibodies do not arise to the noncleaving glycoprotein hormone receptors. Recently, TSAb's were found to preferentially recognize shed, rather than attached, A subunits. Here we use a new adenovirus-mediated animal model of Graves disease to show that goiter and hyperthyroidism occur to a much greater extent when the adenovirus expresses the free A subunit as opposed to a genetically modified TSHR that cleaves minimally into subunits. These data show that shed A subunits induce or amplify the immune response leading to hyperthyroidism and provide new insight into the etiology of Graves disease.

Thyroglobulin-thyroperoxidase autoantibodies are polyreactive, not bispecific: analysis using human monoclonal autoantibodies.

Abstract: Autoantibodies (Ab) to thyroglobulin (Tg) and to thyroid peroxidase (TPO) are reported to share common epitopes, and an assay for bispecific TgPOAb has been developed that may distinguish between different clinical presentations of thyroid autoimmunity. We sought to clone TgPOAb from an Ig gene combinatorial library constructed from B cells infiltrating the thyroid of a patient with TgPOAb. As described for isolating serum TgPOAb, we panned the phage display library by alternating from Tg- to TPO-coated ELISA wells. After panning, the library was enriched for TgPO-binding phage. Of 526 clones tested for expressed Ab, most were negative; 3 clones were specific for Tg, and 5 clones specifically recognized TPO. Antibody from a single clone, encoded by a non-Tg, non-TPO Ig heavy chain gene, bound both Tg and TPO (TgPO activity). However, this antibody also bound equally well to nonthyroid antigens. In conclusion, enrichment for Tg- and TPO-binding phage was largely attributable to phage specific for either Tg or TPO. This finding, albeit from a single patient, questions previous observations of serum TgPOAb prepared by affinity chromatography. Combined with the isolation of a polyreactive monoclonal antibody, our data provide powerful evidence against shared, cross-reactive epitopes on 2 major thyroid autoantigens.