| Background: Previous study suggested Ig G4 levels are associated with the development and grade of Graves’ ophthalmopathy(GO)in Graves’ disease(GD)patients.The aims of the present study were to analyze the possible correlations between serum Ig G4 levels and GO,and to investigate the role of Ig G4 levels for glucocorticoids(GC)treatment in GO patients.Methods: In this prospective study,fifty GO patients were enrolled.Serum thyroid hormones,thyroid autoantibodies,immunoglobulin G(Ig G),Ig G4,ophthalmological examinations and orbital MRI were performed.According to rigors screening,highdose intravenous glucocorticoids(500 mg for the first 6 weeks,250 mg for the last 6 weeks,once a week)were administrated to 31 GO patients.All the subjects underwent Ig G,Ig G4,thyroid-associated antibody,ophthalmological examinations and orbital MRI before and after treatment.The response rate(a composite response endpoint including Clinical Activity Score,exophthalmos,visual acuity,intraocular pressure,diplopia and lid width)was evaluated as the primary outcome,and adverse effects were recorded at each visit.Results: 1.The correlation between serum Ig G4 level and clinical and laboratory indicators In 50 GO patients were enrolled,according to the EUGOGO,these patients were divided into mild group,moderate-severe group and DON group.Ig G4 levels were significantly positively correlated with disease severity(r=0.300,P=0.034),TPOAb(r=0.292,P=0.040),TGAb(r=0.290,P=0.041),and TRAb(r=0.390,P=0.005),whereas no correlation was found between Ig G4 and age,smoking history,thyroid function,ophthalmic assessments results(CAS,exophthalmos,vision,intraocular pressure),or MRI results(EOM,T2 RT,lacrimal gland area)(P>0.05).2.The changes of clinical and laboratory parameters after GC therapy Thirty-one patients from part 1 underwent GC treatment.Compared with before treatment,Ig G4(W0 vs.W12,91.7±68.3 vs.61.2±39.9 mg/d L,P<0.001)and Ig G(W0 vs.W12,1218.2±298.3 vs.973.6±196.4 mg/d L,P<0.001)levels and the ratio of Ig G4/Ig G(W0 vs.W12,7.22±4.60 vs.6.16±3.57 %,P=0.002)were markedly decreased.While the antibodies,including TPOAb(W0 vs.W12,113.02±180.91 vs.76.13±157.85 IU/m L,P=0.007)and TRAb(W0 vs.W12,13.56±12.26 vs.5.31±6.20 IU/L,P<0.001),also decreased notably(P<0.05),there was almost no changes TGAb after 12 weeks of treatment(P>0.05).There were variable changes in the findings of MRI.The T2RT(W0 vs.W12,81.09±5.83 vs.77.85±4.44 ms,P=0.003),axial lacrimal gland area(W0 vs.W12,65.17±26.68 vs.50.69±16.82 mm2,P=0.002)and coronal lacrimal gland(W0 vs.W12,63.10±27.08 vs.48.21±19.92 mm2,P<0.001)area improved markedly(P<0.05),whereas there was no difference in EOM areas even after treatment(W0 vs.W12,55.07±14.00 vs.50.85±13.52 mm2,P=0.063).3.Analysis of the clinical outcomes in the normal Ig G4 and high Ig G4 groups after GC treatment Patients were divided into a normal Ig G4 group(n=17)and a high Ig G4 group(n=14)based on Ig G4 levels in these 31 patients.Compared with before treatment,the clinical outcomes,including the CAS,exophthalmos,vision,intraocular pressure,diplopia,and lid width were evaluated in both groups.The high Ig G4 group(85.7%)had a much higher percentage of improvement than the normal Ig G4 group(58.8%).Additionally,in the high Ig G4 group,EOM areas were significantly decreased(W0 vs.W12,56.32±14.07 vs.46.83±10.91,P=0.024),whereas this parameter were unchanged in the normal Ig G4 group.Conclusions: 1.Our results demonstrated that Ig G4 levels were increased in DON patients compared with patients with mild and moderate-severe GO.Furthermore,increasing Ig G4 levels were associated with thyroid antibodies and,the development and grade of GO but not with other parameters associated with the thyroid or eyes.2.After intravenous GC treatment,the Ig G4,Ig G,Ig G4/Ig G ratio,TPOAb and TRAb in GO patients were significantly decreased.In addition,we also found that the area of lacrimal gland in GO patients decreased significantly after treatment.3.After 12 weeks of GC therapy,our results demonstrated that GO patients with higher levels of Ig G4 might have a better curative effect.Our findings suggested that a possible have a subgroup of elevated Ig G4 GO patients with high Ig G4 levels,more severe,and better response to GC treatment compare. |
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