Preliminary Study On The Relationship Between IgG4and Systemic Lupus Erythematosus

Backgrounds:Systemic lupus erythematosus (SLE) is an autoimmune diseases for theclinical features of multi-system and multi-organ involvement, which has awide range of immunological abnormalities. The cellular immunity andhumoral immune system disorders throughout the entireprocess of SLE, Bcells directly involved in the pathogenesis of SLE, the immune dysfunction ischaracterized by the body to produce a variety of autoantibodies.Immune globulin G (IgG) is the highest levels of immunoglobulin inserum, it is the primary antibody in the blood and extracellular fluid, play asignificant immunological effects, such as conditioning effect,antibody-dependent cell-mediatedcytotoxicity(ADCC), and anti-inflammatoryeffects. IgG can be divided into IgG1~IgG4four subclasses in accordancewith the different heavy chain amino acid, IgG1is the major subclasses, thecurrently detected autoantibodies of SLE mainly IgG1subtype; IgG4isrelatively rare expression subtype of the IgG, and it is low affinity for thetarget antigen, so can not bind to the C1q complement and to activate theclassical complement pathway, but it can suppression the immune complexesformed of the other subtypes.The generation of IgG4is similar as IgE, it is produced by B cells whichregulated by cytokines such as interleukin-4(IL-4), IL-13secreted by Th2,previous studies showed that the IgG4related to allergic diseases. Recentstudies have found that significantly higher levels of IgG4and IgG4-positiveplasma cell infiltration in IgG4-related diseases, such as autoimmune pancreatitis, sclerosing cholangitis, Mikulic disease, retroperitoneal fibrosis,hypophysitis, interstitial pneumonitis, interstitial nephritis, organinflammatory pseudotumor etc. There are a few reports found autoantibodiesof the IgG4subtype or IgG4-positive plasma cell infiltration in autoimmunediseases such as rheumatoid arthritis and systemic lupus erythematosus. Butthe etiology of IgG4-related disease and the function of IgG4inabove-mentioned diseases is not clear, so the study of IgG4with thepathogenesis of autoimmune diseases has become a hot topic.Objective:1. Through detecting the levels of IgG4in plasma of systemic lupuserythematosus (SLE), and plasma levels with healthy controls, to analyze andexplore the clinical significance of IgG4in patients of SLE.2. To investigate the significance of autoantibodies of IgG4subclass inthe pathogenesis of SLE by detecting serum autoantibodies of IgG4subclassin SLE patients.Methods:1. The levels of IgG4in plasma from57patients of SLE and41healthy controls were detected by enzyme linked immunosorbentassay(ELISA), and analysis the differences of clinical indicators in groups ofelevated levels of IgG4and normal.2. The serum autoantibodies of IgG4subclass from59patients of SLEand41healthy controls were detected by bands immunoblotting(IBT), furtherto explore the role of IgG4in the pathogenesis of SLE.Results:1. The plasma levels of IgG4in SLE patients was3.16±2.81g/L,significantly higher than that1.22±0.87g/L in healthy controls (P=0.000).2. With Interstitial pneumonia and elevated Pancreatic involvement(including elevated blood pancreatic amylase and lipaseenzymes) in SLEpatients which plasma levels of IgG4elevated were significantly higher thanplasma levels of IgG4normal (P=0.014, P=0.015).3. With autoantibodies of IgG4subclass positive in30of59patients ofSLE(including IgG4anti-Nucleosome antibodies, IgG4anti-snRNPantibodies, IgG4the anti-RibP-Prot antibodies, IgG4anti-Ro52antibodies,IgG4anti-SSA antibodies, IgG4anti-SmD antibodies, IgG4anti-SSBantibodies and IgG4anti-CENPB antibodies), neither the aboveautoantibodies of IgG4subclass positive in41healthy controls; Addition, itwas found that IgG4anti-dsDNA antibodies positive in all of the59patientsof SLE and41healthy controls.4. The incidence of Raynaud’s phenomenon, Haematologicalinvolvement and Interstitial pneumonia was significantly higher in patients ofSLE which autoantibodies of IgG4subclass positive than negative group (P=0.006, P=0.041, P=0.023).Conclusion:1. The plasma levels of IgG4in SLE patients was significantly higherthan in group of control, the patients of SLE which plasma levels of IgG4elevated are more vulnerable to occur Interstitial pneumonia and Pancreaticinvolvement, suggesting that IgG4may play a role in the pathogenesis ofSLE.2. The autoantibodies of IgG4subclass existed in SLE patients, thepatients of SLE which autoantibodies of IgG4subclass positive are morelikely to develop Raynaud’s phenomenon, Haematological involvement and Interstitial pneumonia.