| BackgroundsIgA nephropathy(IgAN)is the most common primary glomerular disease.About 40%of patients with IgAN can develop end stage renal disease(ESRD)within 20 years.Although there is an absence of a thorough understanding of its pathogenesis,Galactose-deficient IgAl(Gd-IgAl)is detected in both serum and glomeruli of patients with IgAN,which may participate in pathogenesis of IgAN.Patients with IgAN had higher levels of serum Gd-IgAl compared to healthy controls,but immunosuppressive therapy may interfere with this conclusion and cause deviation.Meanwhile,the relationship between serum Gd?IgAl and clinical and pathological severity of IgAN is currently controversial in previous researches.The clinical manifestations of some cases of IMN are similar to those of IgAN,There is no research about whether serum Gd-IgAl could help the initial differentiation between IMN and IgAN.What' s more,it' s worthy to further research whether serum Gd-IgAl at baseline correlates to curative effects and prognosis of IgAN.Objects1.To confirm whether there is difference among the serum Gd-IgAl levels in IgAN,MN and healthy controls.To evaluate the ability of serum Gd-IgAl to distinguish IgAN from IMN;2.To explore the relationship between serum Gd-IgAl and the clinical manifestations and renal pathological severity of IgAN;3.To explore whether serum Gd-IgAl at baseline can predict the clinical manifestations of IgAN after short-term therapy.And to evaluate the relationship between changes of serum Gd-IgAl and changes of IgAN severity.MethodsPatients with biopsy proven IgAN and MN and healthy controls from PUMCH between May.2018 and May.2019 were enrolled.The inclusion criteria for healthy controls are eGFR?60ml/min/1.73m2 and negative urine protein and blood.The exclusion criteria for IgAN are diabetes mellitus,immunosuppressive therapy whthin 1 month and factors for secondary renal IgA deposits including HSPN,Hepatitis B virus,Hepatitis C virus and HIV.The exclusion criteria for IMN are diabetes mellitus,immunosuppressive therapy for more than 2 weeks,renal IgA deposits and factors for secondary membranous nephropathy,we measure serum Gd-IgAl of enrolled IgAN,MN and healthy controls with anti-Gd-IgAl antibody ELISA kit.Meanwhile we collected the the clinical and pathological parameters at baseline and the clinical parameters during the follow-up period.Results56 IgAN patients,17 IMN patients and 22 healthy controls were enrolled.44 IgAN patients and 17 IMN patients tested serum anti-PLA2R antibody.anti-PLA2R antibody of 11 IMN patients were positive and the rest were negative.1.Serum Gd-IgAl levels were significantly elevated in patients with IgAN compared with healthy controls(4.27(3.46,5.45)vs 2.34(1.87,3.04)ug/ml,P<0.001)and IMN(3.44(2.59,3.98)ug/ml,P=0.009).Among IgAN and healthy controls,the area under curve(AUC)of serum Gd-IgAl as a diagnostic test is 0.877 and when the cut-off value is 2.93ug/ml,the sensitivity is 94.6%,with specificity 77.3%.Among IgAN and IMN,the area under curve(AUC)of serum Gd-IgAl as a diagnostic test is 0.721 and when the cut-off value is 3.99ug/ml,the sensitivity is 60.7%,with specificity 82.4%.Through crosstab,we identify that when combination of serum Gd-IgAl?3.99 ug/ml and anti-PLA2R antibody is a diagnosis test,the sensitivity for distinguishing IgAN from IMN is 56.8Y with specificity 94-1%.2.In IgAN,serum Gd-IgAl has positive correlation with serum IgA(r=0.34,P<0.05).Gd-IgAl/C3 has positive correlation with C3 deposits in glomeruli(r=0.27,P=0.047)and don' t correlate with Scr,Alb,24hUPro,eGFR,glomerular IgA and IgG deposits and the Oxford classification of IgAN(P>0.05).Serum Gd-IgAl and serum Gd-IgAl/IgA don,t correlate with Scr,Alb,24hUPro,eGFR,glomerular IgA,IgG and C3 deposits and the Oxford classification of IgAN(P?0.05).3.The baseline value of serum Gd-IgAl don' t correlate with TA-UP,24 hUPro,change rate of 24hUPro after immunosuppressive therapy and after non-immunosuppressive therapy(P>0.05).When 24hUPro decreased(2.02(0.63,2.88)g/d to 0.55(0.18,0.92)g/d,/P<0.05)and Alb improved(38.9±3.9g/L to 43.8±3.1g/L,P?0.05)significantly after treatment(P?0.05),serum Gd-IgAl don' t change significantly(P=0.13).And the change rate of ser um Gd-IgAl don' t correlate with the change rate of Alb,24hUPro and Scr(P>0.05).Conclusions1. When the cut-off value of serum Gd-IgAl is 2,93ug/ml,the sensitivity is high with limited specificity for distinguishing IgAN from healthy controls,,which indicates serum Gd-IgAl is a suitable marker for eliminating IgAN.2.The combination of serum Gd-IgAl?3.99ug/ml and anti-PLA2R antibody could distinguish IgAN from IMN with higher specificity than using serum Gd-IgAl alone.3.We don' t find correlation between serum Gd-IgAl and the clinical manifestations and renal pathological severity of IgAN.4.We don' t find correlation between serum Gd-IgAl at baseline and clinical manifestations of IgAN after short-term therapy.And we don' t find correlation between changes of serum Gd-IgAl and IgAN progression. |
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