The MHC class I-like Fc receptor promotes humorally mediated autoimmune disease.
The MHC class I family-like Fc receptor, FcRn, is normally responsible for extending the life span of serum IgG Ab's, but whether this molecule contributes to autoimmune pathogenesis remains speculative. To determine directly whether this function contributes to humoral autoimmune disease, we examined whether a deficiency in the FcRn heavy chain influences autoimmune arthritis in the K/BxN mouse model. FcRn deficiency conferred either partial or complete protection in the arthritogenic serum transfer and the more aggressive genetically determined K/BxN autoimmune arthritis models. The protective effects of an FcRn deficiency could be overridden with excessive amounts of pathogenic IgG Ab's. The therapeutic saturation of FcRn by high-dose intravenous IgG (IVIg) also ameliorated arthritis, directly implicating FcRn blockade as a significant mechanism of IVIg's anti-inflammatory action. The results suggest that FcRn is a potential therapeutic target that links the initiation and effector phases of humoral autoimmune disease.
Akilesh
Shreeram
S
The Jackson Laboratory, Bar Harbor, Maine, USA.
Petkova
Stefka
S
Sproule
Thomas J
TJ
Shaffer
Daniel J
DJ
Christianson
Gregory J
GJ
Roopenian
Derry
D
D000818:Animals; D000906:Antibodies / Q000097:blood / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000473:pathology; D001327:Autoimmune Diseases / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D005121:Extremities / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011961:Receptors, Fc / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D044967:Serum / Q000378:metabolism; D019076:Transgenes
D000906:Antibodies; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D011961:Receptors, Fc