Impaired caspase-3 expression by peripheral T cells in chronic autoimmune thyroiditis and in autoimmune polyendocrine syndrome-2.
BACKGROUND
Activation-induced cell death (AICD) is a major mechanism in the regulation of peripheral tolerance, and caspase-3 represents its major executioner. AICD impairment contributes to the persistence of autoreactive T cells, and defective AICD has been reported in autoimmune thyroiditis as well as in type 1 diabetes mellitus.


OBJECTIVE
The objective of this study was to evaluate the involvement of caspase-3 in the regulation of AICD resistance in thyroid and polyendocrine autoimmunity. DESIGN/SETTINGS/PATIENTS/INTERVENTION: Caspase-3 expression was analyzed in peripheral blood lymphocytes from 26 adults (A-AT) and 25 children (Y-AT) affected by autoimmune thyroiditis and 13 individuals affected by chronic autoimmune thyroiditis plus Addison's disease [autoimmune polyendocrine syndrome-2 (APS-2)] in comparison with 32 age-matched normal control subjects (NC).


METHODS
Caspase-3 mRNA expression in peripheral T cells was evaluated by quantitative real-time PCR; protein expression of both procaspase-3 and activated caspase-3 by Western blot analysis was followed by scanning densitometry.


RESULTS
Caspase-3 mRNA expression was significantly reduced in resting lymphocytes from both A-AT (P = 0.001) and Y-AT (P = 0.016) compared with NC. After lymphocyte activation, protein levels of caspase-3 active form were significantly reduced in A-AT (P = 0.023) and Y-AT (P = 0.001) compared with NC. The APS-2 group displayed characteristics similar to the A-AT group because both caspase-3 mRNA and protein active form levels were significantly reduced compared with NC (P = 0.004 and 0.002, respectively).


CONCLUSIONS
Our data show that peripheral lymphocytes of subjects affected by thyroid autoimmunity or APS-2 show defective expression of the major executioner of AICD, thus potentially contributing to AICD resistance and to the development of autoimmunity.
Vendrame
Francesco
F
Diabetes Unit, Department of Internal Medicine, University of Siena, Siena, Italy.
Segni
Maria
M
Grassetti
Daniele
D
Tellone
Valeria
V
Augello
Giovanni
G
Trischitta
Vincenzo
V
Torlontano
Massimo
M
Dotta
Francesco
F
D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D016022:Case-Control Studies; D053148:Caspase 3 / Q000378:metabolism*; D002648:Child; D002908:Chronic Disease; D005260:Female; D015870:Gene Expression; D015971:Gene Expression Regulation, Enzymologic; D020249:Hormone Replacement Therapy; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D016884:Polyendocrinopathies, Autoimmune / Q000201:enzymology* / Q000628:therapy; D013601:T-Lymphocytes / Q000201:enzymology*; D013967:Thyroiditis, Autoimmune / Q000201:enzymology* / Q000628:therapy
D053148:Caspase 3