RESUMO
A cohort of 10 Hashimoto's encephalopathy (HE) patients, 33 patients with unrelated neurological symptoms, 12 Hashimoto's thyroiditis patients and 4 healthy adult donors was studied to explore the neurological targets of anti-thyroperoxidase (TPO) autoantibodies (aAb) in HE. High levels of anti-TPO aAb were only detected in HE group's cerebrospinal fluids. In immunofluorescence assays on monkey brain cerebellum sections, both HE patients' sera and anti-TPO monoclonal antibodies (mAb) were able to bind cerebellar cells expressing glial fibrillary acid protein. Normal human astrocytes from primary cultures also reacted with anti-TPO mAb. Specific astrocyte binding of anti-TPO aAb suggests a role of these aAb in the HE pathogenesis.
Assuntos
Astrócitos/metabolismo , Autoanticorpos/análise , Cerebelo/patologia , Doença de Hashimoto/imunologia , Iodeto Peroxidase/imunologia , Tireoglobulina/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Autoanticorpos/imunologia , Células Cultivadas , Cerebelo/metabolismo , Feminino , Feto , Proteína Glial Fibrilar Ácida/metabolismo , Doença de Hashimoto/patologia , Humanos , Iodeto Peroxidase/sangue , Iodeto Peroxidase/líquido cefalorraquidiano , Masculino , Pessoa de Meia-Idade , Radioimunoensaio , Tireoglobulina/sangue , Tireoglobulina/líquido cefalorraquidiano , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia , Fatores de TempoRESUMO
Deiodinases (D1, D2, and D3) are selenoproteins involved in thyroid hormone metabolism. Generation of the active hormone T(3), from T(4), is carried out by D1 and D2, whereas D3 degrades both hormones. The identity of the cloned D2 as a selenoprotein is well supported by biochemical and physiological data. However, an alternative view has proposed that type 2 deiodinase is a nonselenoprotein complex containing a putative T(4) binding subunit called p29, with an almost identity in sequence with the Dickkopf protein Dkk3. To explore a possible functional relationship between p29 and D2, we have compared their mRNA expression patterns in the rat brain. In brain, parenchyma p29 was expressed in neurons. High expression levels were found in all the regions of the blood-cerebrospinal fluid (CSF) barrier. p29 was present in different types of cells than D2, with the exception of the tanycytes. Our data do not support that p29 has a functional relationship with D2. On the other hand, expression of p29 in the blood-CSF barrier suggests that it might be involved in T(4) transport to and from the CSF, but further studies are needed to substantiate this hypothesis.