FCgammaRII (CD32)-dependent induction of interferon-alpha by serum from patients with lupus erythematosus.
Interferon-alpha (IFN-alpha) is detected in the serum of 70-80% of patients with systemic lupus erythematosus (SLE). Furthermore, soluble factors in SLE serum can induce peripheral blood mononuclear cells (PBMC) to produce IFN-alpha. The purpose of this work was to investigate the mechanism of this IFN-alpha induction. In eleven of fifteen SLE serum samples, an IFN-alpha inducing activity was detected, whereas serum from healthy controls, patients with other autoimmune disease and patients with viral infections were ineffective under the same conditions. After gel filtration of the serum, the inducing activity was found in the same fraction as IgG. The IFN-alpha inducing activity was inhibited by native monoclonal antibodies to the receptors for the Fc portion of IgG: FcgammaRIIA/C and FcgammaRIIB subclasses (CD32) and by their F(ab)'2 fragments. Purified Fc fragments of human IgG were also effective in abolishing the IFN-alpha-inducing activity. Since no anti-CD32 autoantibodies were found in SLE serum, this IFN-alpha-inducing activity may be due to immune complex antibodies. Such results may allow better understand the origin of endogenous IFN-alpha, which has a deleterious effect on the course of this autoimmune disease. The inhibition of this function by the CD32 antibody could lead to new therapeutic approach in SLE.
Batteux
F
F
Hopital Saint-Vincent-de-Paul, 82, avenue Denfert-Rochereau, 75014 Paris Cedex 14, France.
Palmer
P
P
Daëron
M
M
Weill
B
B
Lebon
P
P
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000936:Antigen-Antibody Complex / Q000276:immunology; D001323:Autoantibodies / Q000032:analysis / Q000276:immunology; D001327:Autoimmune Diseases / Q000097:blood; D001798:Blood Proteins / Q000737:chemistry / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology*; D002478:Cells, Cultured; D002850:Chromatography, Gel; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007141:Immunoglobulin Fc Fragments / Q000276:immunology / Q000494:pharmacology; D007074:Immunoglobulin G / Q000276:immunology / Q000302:isolation & purification; D016898:Interferon-alpha / Q000096:biosynthesis* / Q000097:blood / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000276:immunology / Q000378:metabolism*; D018448:Models, Immunological; D017452:Receptors, IgG / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*; D012995:Solubility
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D001798:Blood Proteins; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D016898:Interferon-alpha; D017452:Receptors, IgG