The Characteristics And Clinical Significance Of Elevated Serum IgG4/IgG Levels In Patients With Graves’ Disease

Background and Purpose:IgG4-related disease(IgG4-RD)is a systemic disease involving various organs in the whole body,and the thyroid is also one of the organs involved.Previous studies have shown that Graves with elevated IgG4 levels is one of the subtypes of IgG4-related thyroid diseases.Graves’disease(GD)with high serum IgG4 levels and GD without high serum IgG4 levels have different clinical and laboratory characteristics,but there are differences in research results.This study aims to further explore the clinical and laboratory characteristics of GD patients with high serum IgG4 based on IgG4/IgG ratio,longitudinally analyze the changes in IgG4 levels and cytokines in GD patients before and after treatment,and the correlation between various experimental parameters.Mothods:This study is a prospective observational study.A total of 20 non-GD patients were enrolled as the control group and 84 newly diagnosed GD patients were enrolled as the case group.among which 66 GD patients completed the 3-month follow-up in the case group.All the enrolled experimental group patients and the experimental group patients who completed the 3-month follow-up and the control group need to be tested for thyroid hormones(FT3,FT4,TSH),thyroid immune resistance(TPOAb,TGAb,TRAb),IgG,IgG4,And cytokines(IL-1β,IL-4,IL-10,IL-17,TNF-α).The case groups were treated with the same dose of antithyroid drugs(ATD).Patients who were followed up for 1 month and 2 months of treatment only tested thyroid hormones and thyroid immune antibodies.With the IgG4/IgG ratio of 8%as the cut-off value,GD patients were divided into two groups:high IgG4/IgG group and low IgG4/IgG group.Compare the general conditions,baseline levels of thyroid hormones,thyroid immune antibodies,cytokines,and treatment effects between the two groups,and observe before and after treatment The changes between the two groups of indicators.Results:(1)The differences in thyroid hormone levels,thyroid immune antibody titer,IgG4,IgG4/IgG and IL-17 between the GD group and the normal control group were statistically significant(P<0.05),while IgG and cytokines(IL-1β,IL-4,IL-10,TNF-α)were not statistically different between the two groups(P>0.05).(2)In 84GD patients,25 in the high IgG4/IgG group and 59 in the low IgG4/IgG group,the differences in age,IL-1β,IL-17 and eosinophil count between the two groups were statistically significant(P values were respectively 0.022,0.037,0.007,0.021);while gender,IL-4,IL-10,TNF-α,thyroid hormone levels and thyroid immune antibody levels were not significantly different between the two groups(P>0.05).The results of correlation analysis showed that age was significantly negatively correlated with IgG4(r=-0.270,P=0.013)and IgG4/IgG levels(r=-0.292,P=0.007);while eosinophils were significantly positively correlated with IgG4(r=0.236,P=0.046)and IgG4/IgG levels(r=0.279,P=0.030).(3)After ATD treatment,some patients developed allergies.Among them,there were 9 cases in the high IgG4/IgG group(37.5%,9/24),and 9 cases in the low IgG4/IgG group(16.1%,9/56).The difference was statistically significant(χ~2=4.424,P=0.035).(4)After 3 months of treatment in GD patients,the levels of IgG and TRAb in the low IgG4/IgG group were significantly lower than before(P<0.05);while the TRAb levels in the high IgG4/IgG group were lower than before treatment,but the difference was not statistically significant(P>0.05);The differences in IgG4 and IgG4/IgG between the high IgG4/IgG level group and the low IgG4/IgG level group were statistically significant(P<0.05),while the differences in thyroid hormone levels,TRAb,IgG,and cytokines were not statistically significant between the two groups.Conclusions:The IgG4 and IgG4/IgG levels of GD patients were significantly higher than those of non-GD normal controls.Compared with GD patients with low IgG4/IgG levels,GD patients with high IgG4/IgG levels have different characteristics:they are younger,have higher eosinophils,IL-1βand IL-17,are not easily relieved after ATD treatment,and are more prone to allergic reactions to ATD,which may be related to the instability of Th17/Treg cell balance.