title: IgG1 deficiency exacerbates experimental autoimmune myasthenia gravis in BALB/c mice.
abstract: Myasthenia gravis is an autoimmune disease characterized by muscle weakness due to neuromuscular junction (NMJ) damage by anti-acetylcholine receptor (AChR) auto-antibodies and complement. In experimental autoimmune myasthenia gravis (EAMG), which is induced by immunization with Torpedo AChR in CFA, anti-AChR IgG2b and IgG1 are the predominant isotypes in the circulation. Complement activation by isotypes such as IgG2b plays a crucial role in EAMG pathogenesis; this suggested the possibility that IgG1, which does not activate complement through the classical pathway, may suppress EAMG. In this study, we show that AChR-immunized BALB/c mice genetically deficient for IgG1 produce higher levels of complement-activating isotypes of anti-AChR, especially IgG3 and IgG2a, and develop increased IgG3/IgG2a deposits at the NMJ, as compared to wild type (WT) BALB/c mice. Consistent with this, AChR-immunized IgG1(-/-) BALB/c mice lose muscle strength and muscle AChR to a greater extent than AChR-immunized WT mice. These observations demonstrate that IgG1 deficiency leads to increased severity of EAMG associated with an increase in complement activating IgG isotypes. Further studies are needed to dissect the specific role or mechanism of IgG1 in limiting EAMG and that of EAMG exacerbating role of complement activating IgG3 and IgG2a in IgG1 deficiency.
authors: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555-1070, USA. Electronic address: rhuda@utmb.edu.
authors: Ruksana
authors: R
authors: Huda
authors: Division of Emergency Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45267, USA.
authors: Richard T
authors: RT
authors: Strait
authors: Department of Neuroscience, Institute for Experimental Medical Research, University of Istanbul, Istanbul 34390, Turkey.
authors: Erdem
authors: E
authors: Tüzün
authors: Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, University of Cincinnati, College of Medicine, Cincinnati, OH 45267, USA; Department of Medicine, Cincinnati Veterans Affairs Medical Center, Cincinnati, OH 45220, USA.
authors: Fred D
authors: FD
authors: Finkelman
authors: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555-1070, USA. Electronic address: pchrista@utmb.edu.
authors: Premkumar
authors: P
authors: Christadoss
mesh_terms: D000818:Animals; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism*; D014101:Torpedo
chemical_list: D007074:Immunoglobulin G
keywords: Acetylcholine receptor; Autoimmunity; Experimental autoimmune myasthenia gravis; IgG1; IgG3; Myasthenia gravis