Expression and function of multiple regulators of complement activation in autoimmune thyroid disease.
Membrane attack complexes of complement occur around thyroid follicles in Graves' disease and Hashimoto's thyroiditis. The lytic potential of such complexes is controlled by membrane-bound and fluid phase regulators and we have investigated the role of these in autoimmune thyroid disease. By immunohistochemical staining, clusterin and S-protein were found in all nine thyroid specimens from patients with Graves' disease and S-protein was found in one of two Hashimoto glands. CD46, CD55 and CD59 were found on thyroid cells in all specimens. CD46 and CD55 expression occurred on thyroid cells cultured in vitro and was increased significantly by culture with interleukin-1 (IL-1) and interferon-gamma (IFN-gamma), which are known to be released by the lymphocytic infiltrate in these conditions. Blocking CD55 had a weak and inconsistent effect on complement-mediated thyroid cell killing in vitro but, in four of five experiments, blocking CD46 enhanced killing. However, the effect of blocking CD59 was greater in all cases than blocking CD46 or CD55. Expression of these fluid phase and membrane-bound proteins may be important in determining the severity of thyroid damage produced by complement fixation in Graves' disease and Hashimoto's thyroiditis.
Tandon
N
N
Department of Medicine, University of Sheffield Clinical Sciences Centre, Northern General Hospital, U.K.
Yan
S L
SL
Morgan
B P
BP
Weetman
A P
AP
D015703:Antigens, CD / Q000032:analysis; D001327:Autoimmune Diseases / Q000276:immunology*; D018958:CD55 Antigens; D018957:CD59 Antigens; D002478:Cells, Cultured; D051152:Clusterin; D003167:Complement Activation / Q000276:immunology*; D003169:Complement Inactivator Proteins / Q000032:analysis*; D015938:Complement Membrane Attack Complex / Q000037:antagonists & inhibitors; D005434:Flow Cytometry; D006023:Glycoproteins / Q000032:analysis; D006111:Graves Disease / Q000276:immunology; D006801:Humans; D007124:Immunoenzyme Techniques; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000032:analysis; D018832:Molecular Chaperones; D013959:Thyroid Diseases / Q000276:immunology*; D013961:Thyroid Gland / Q000276:immunology*; D013967:Thyroiditis, Autoimmune / Q000276:immunology; D019096:Vitronectin
D015703:Antigens, CD; C497857:CD46 protein, human; D018958:CD55 Antigens; D018957:CD59 Antigens; C495242:CLU protein, human; D051152:Clusterin; D003169:Complement Inactivator Proteins; D015938:Complement Membrane Attack Complex; D006023:Glycoproteins; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D019096:Vitronectin