A role for autoantibodies in enhancement of pro-inflammatory cytokine responses to a self-antigen, thyroid peroxidase

TY - JOUR

T1 - A role for autoantibodies in enhancement of pro-inflammatory cytokine responses to a self-antigen, thyroid peroxidase

AU - Nielsen, Claus H

AU - Brix, Thomas H

AU - Leslie, R Graham Q

AU - Hegedüs, Laszlo

N1 - Keywords: Adult; Aged; Antibodies; Autoantibodies; Autoantigens; Cytokines; Female; Hashimoto Disease; Humans; Immune Sera; Immunoglobulin G; Interferon-gamma; Interleukin-10; Interleukin-4; Interleukin-6; Iodide Peroxidase; Leukocytes, Mononuclear; Male; Middle Aged; Phagocytes; Receptors, IgG; T-Lymphocytes; Tetanus Toxoid; Tumor Necrosis Factor-alpha

PY - 2009

Y1 - 2009

N2 - The role of thyroid peroxidase (TPO) antibodies (TPOAbs) in the pathogenesis of autoimmune thyroid disease is unclear. We selected sera with a high concentration of TPOAbs from eleven patients with Hashimoto's thyroiditis (HT), ten healthy monozygotic co-twins to HT patients, and twelve healthy individuals with no familiar disposition to AITD, and mixed each serum with normal mononuclear cells (MNCs). Following challenge with TPO, the MNCs' production of the pro-inflammatory cytokines TNF-alpha, IL-6 and IFN-gamma, and the anti-inflammatory cytokine IL-10, correlated with the TPOAb content of the serum present in the culture (p=0.0002-0.05). Enrichment of foetal calf serum-containing media with IgG with a high content of TPOAbs enhanced the TPO-elicited production of TNF-alpha, IL-6 and IFN-gamma by normal MNCs in a dose- and Fcgamma-receptor dependent manner (p<0.0002-0.05). The data indicate that TPO-induced release of pro-inflammatory cytokines from phagocytic cells and T-cell responses to TPO are promoted by TPOAbs.

AB - The role of thyroid peroxidase (TPO) antibodies (TPOAbs) in the pathogenesis of autoimmune thyroid disease is unclear. We selected sera with a high concentration of TPOAbs from eleven patients with Hashimoto's thyroiditis (HT), ten healthy monozygotic co-twins to HT patients, and twelve healthy individuals with no familiar disposition to AITD, and mixed each serum with normal mononuclear cells (MNCs). Following challenge with TPO, the MNCs' production of the pro-inflammatory cytokines TNF-alpha, IL-6 and IFN-gamma, and the anti-inflammatory cytokine IL-10, correlated with the TPOAb content of the serum present in the culture (p=0.0002-0.05). Enrichment of foetal calf serum-containing media with IgG with a high content of TPOAbs enhanced the TPO-elicited production of TNF-alpha, IL-6 and IFN-gamma by normal MNCs in a dose- and Fcgamma-receptor dependent manner (p<0.0002-0.05). The data indicate that TPO-induced release of pro-inflammatory cytokines from phagocytic cells and T-cell responses to TPO are promoted by TPOAbs.

U2 - 10.1016/j.clim.2009.07.014

DO - 10.1016/j.clim.2009.07.014

M3 - Journal article

C2 - 19726232

SN - 1521-6616

VL - 133

SP - 218

EP - 227

JO - Clinical Immunology

JF - Clinical Immunology

IS - 2

ER -