A role for autoantibodies in enhancement of pro-inflammatory cytokine responses to a self-antigen, thyroid peroxidase.
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.
Nielsen
Claus H
CH
Department of Clinical Immunology, section 7631, Rigshospitalet University Hospital, Copenhagen, Denmark. c.h.nielsen@rh.regionh.dk
Brix
Thomas H
TH
Leslie
R Graham Q
RG
Hegedüs
Laszlo
L
D000328:Adult; D000368:Aged; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D050031:Hashimoto Disease / Q000276:immunology*; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007453:Iodide Peroxidase / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010586:Phagocytes / Q000276:immunology / Q000378:metabolism; D017452:Receptors, IgG / Q000037:antagonists & inhibitors / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013745:Tetanus Toxoid / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000906:Antibodies; D001323:Autoantibodies; D001324:Autoantigens; D016207:Cytokines; C508609:IL10 protein, human; C508598:IL4 protein, human; C508600:IL6 protein, human; D007106:Immune Sera; D007074:Immunoglobulin G; D015850:Interleukin-6; D017452:Receptors, IgG; D013745:Tetanus Toxoid; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D007453:Iodide Peroxidase