A pilot and comparative study between pathological and serological levels of immunoglobulin and complement among three kinds of primary glomerulonephritis

Abstract Background Immunoglobulin A nephropathy (IgAN), membranous nephropathy (MN) and minimal-change disease (MCD) are three common types of glomerulonephritis in China. Pathological diagnosis based on renal biopsy is the criterion and the golden standard for diagnosing the sub-types of primary o...

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Main Authors: Jin Dong, Tianhao Peng, Jing Gao, Xingwang Jia, Guangtao Yan, Yong Wang
Format: Article
Language:English
Published: BMC 2018-06-01
Series:BMC Immunology
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Online Access:http://link.springer.com/article/10.1186/s12865-018-0254-z
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author Jin Dong
Tianhao Peng
Jing Gao
Xingwang Jia
Guangtao Yan
Yong Wang
author_facet Jin Dong
Tianhao Peng
Jing Gao
Xingwang Jia
Guangtao Yan
Yong Wang
author_sort Jin Dong
collection DOAJ
description Abstract Background Immunoglobulin A nephropathy (IgAN), membranous nephropathy (MN) and minimal-change disease (MCD) are three common types of glomerulonephritis in China. Pathological diagnosis based on renal biopsy is the criterion and the golden standard for diagnosing the sub-types of primary or secondary glomerulonephritis. Immunoglobulin and complements might be used in the differential diagnosis of glomerulonephritis without renal biopsies. However, the relationship between IF intensities of immune proteins and the corresponding serum levels remained unclear, and seldom studies combine histopathological examination results and blood tests together for a predictive purpose. This study was considered as a pilot study for integrating histopathological indicators into serum parameters for exploring the relationship of IF intensity and serum values of immunoglobulin and complement, and for screening and investigating effective indicators inIgAN, MN and MCD. Methods Renal tissue immunofluorescence (IF) intensity grades and serum levels of immunoglobulin and complements (IgG, IgA, IgM, C3 and C4) were retrospectively analyzed in 236 cases with IgAN, MN or MCD. IF grades were grouped as negative (−), positive (+) or strong positive (++) with both high and low magnification of microscope. Other serum indicators such as urea nitrogen (BUN), creatinine (Crea) and estimated glomerular filtration rate (eGFR) were also evaluated among the groups. Results There were difference in IgA, IgG and C3 IF intensity grades among IgAN, MN and MCD groups (p = 9.82E-43, 4.60E-39, 7.45E-15, respectively). Serum values of BUN, Crea, eGFR, IgG, IgA, IgM and C4 showed difference in three groups (BUN: p = 0.045, Crea: p = 3.45E-5, eGFR: p = 0.005, IgG: p = 1.68E-14, IgA: p = 9.14E-9, IgM: p = 0.014, C4: p = 0.026). eGFR had the trend to decrease with enhanced IgA IF positive grades (p = 8.99E-4); Crea had trends to decrease with both enhanced IgA and IgG IF intensity grades (p = 2.06E-6, 2.94E-5, respectively). In all subjects, serum IgA levels was inversely correlated with eGFR(r = − 0.216, p = 0.001) and correlated with Crea levels(r = 0.189, p = 0.004); serum IgG and Crea showed no correlation which were discordance with inverse correlation of IgG IF grade and Crea(r = 0.058,p = 0.379). IgG serum level was inverse correlated with its IF grades (p = 3.54E-5, p = 7.08E-6, respectively); C3 serum levels had significantly difference between Neg and positive (+) group (p = 0.0003). IgA serum level was positive correlated with its IF grades (Neg-(+): p = 0.0001; (+)-(++): p = 0.022; Neg-(++): p = 2.01E-10). After matching comparison among C3 groups, C3 Neg. group and C3 ++ group had difference (*p = 0.017). C4 had all negative IF expression in all pathological groups. In IgAN subjects, there were statistical differences of serum C3 levels between its pathological Neg and positive (+) group(p = 0.026), and serum IgA levels showed difference between IgA pathological positive(+) and (++)(p = 0.007). In MN subjects, sIgG levels showed difference between IgG pathological IF grade positive (+) and (++)(p = 0.044); serum C3 levels showed difference between C3 pathological IF grade Neg and positive(+)(p = 0.005); and serum IgA levels showed difference between Neg and positive(+)(p = 0.040). In IgAN, eGFR showed serum IgA levels had significant differences among groups (p = 0.007) and had increasing trend with enhanced its IF grades(Ptrend = 0.016). There were also difference between IgG group Neg and positive (+) (p = 0.005, Ptrend = 0.007) in IgAN. In MN, serum IgG levels had significant differences among IF groups (p = 0.034) and had decreasing trend with its enhanced IF grades (Ptrend = 0.014). Serum C3 concentrations also were found distinctive among IF groups (p = 0.016) and had in inverse correlation with its enhanced IF grades (Ptrend = 0.004). Discussion Our research cross contrasts several immunoprotein IF intensities and relevant serum levels in three kinds of primary glomerular nephritis, and finally acquired helpful results for understanding the relationships between pathological presentation and serological presentation of immunoproteins in kidney diseases. Furthermore, this pilot study is offering a possible method for the analysis of combination of pathology and serology. Conclusion Different pathological types of nephritis presented different expression patterns of immunoglobulin and complement, especially IgA and IgG, which suggested different pathogenesis involved in the development of IgAN and MN. Furthermore, either in tissue or in serum, increased IgA level was closely related with renal function in all of the patients.
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spelling doaj.art-15ab2a721ef34d5396928fcc0fcea0f02022-12-22T00:12:34ZengBMCBMC Immunology1471-21722018-06-0119111110.1186/s12865-018-0254-zA pilot and comparative study between pathological and serological levels of immunoglobulin and complement among three kinds of primary glomerulonephritisJin Dong0Tianhao Peng1Jing Gao2Xingwang Jia3Guangtao Yan4Yong Wang5Department of Clinical Biochemistry, Medical Laboratory Center, State Key Laboratory of Kidney Disease, Chinese PLA General HospitalTesting Center of Health Management Institute, Chinese PLA General HospitalDepartment of Clinical Biochemistry, Medical Laboratory Center, State Key Laboratory of Kidney Disease, Chinese PLA General HospitalDepartment of Clinical Biochemistry, Medical Laboratory Center, State Key Laboratory of Kidney Disease, Chinese PLA General HospitalDepartment of Clinical Biochemistry, Medical Laboratory Center, State Key Laboratory of Kidney Disease, Chinese PLA General HospitalDepartment of Nephrology, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Medical Institution Conducting Clinical Trials, Chinese PLA General HospitalAbstract Background Immunoglobulin A nephropathy (IgAN), membranous nephropathy (MN) and minimal-change disease (MCD) are three common types of glomerulonephritis in China. Pathological diagnosis based on renal biopsy is the criterion and the golden standard for diagnosing the sub-types of primary or secondary glomerulonephritis. Immunoglobulin and complements might be used in the differential diagnosis of glomerulonephritis without renal biopsies. However, the relationship between IF intensities of immune proteins and the corresponding serum levels remained unclear, and seldom studies combine histopathological examination results and blood tests together for a predictive purpose. This study was considered as a pilot study for integrating histopathological indicators into serum parameters for exploring the relationship of IF intensity and serum values of immunoglobulin and complement, and for screening and investigating effective indicators inIgAN, MN and MCD. Methods Renal tissue immunofluorescence (IF) intensity grades and serum levels of immunoglobulin and complements (IgG, IgA, IgM, C3 and C4) were retrospectively analyzed in 236 cases with IgAN, MN or MCD. IF grades were grouped as negative (−), positive (+) or strong positive (++) with both high and low magnification of microscope. Other serum indicators such as urea nitrogen (BUN), creatinine (Crea) and estimated glomerular filtration rate (eGFR) were also evaluated among the groups. Results There were difference in IgA, IgG and C3 IF intensity grades among IgAN, MN and MCD groups (p = 9.82E-43, 4.60E-39, 7.45E-15, respectively). Serum values of BUN, Crea, eGFR, IgG, IgA, IgM and C4 showed difference in three groups (BUN: p = 0.045, Crea: p = 3.45E-5, eGFR: p = 0.005, IgG: p = 1.68E-14, IgA: p = 9.14E-9, IgM: p = 0.014, C4: p = 0.026). eGFR had the trend to decrease with enhanced IgA IF positive grades (p = 8.99E-4); Crea had trends to decrease with both enhanced IgA and IgG IF intensity grades (p = 2.06E-6, 2.94E-5, respectively). In all subjects, serum IgA levels was inversely correlated with eGFR(r = − 0.216, p = 0.001) and correlated with Crea levels(r = 0.189, p = 0.004); serum IgG and Crea showed no correlation which were discordance with inverse correlation of IgG IF grade and Crea(r = 0.058,p = 0.379). IgG serum level was inverse correlated with its IF grades (p = 3.54E-5, p = 7.08E-6, respectively); C3 serum levels had significantly difference between Neg and positive (+) group (p = 0.0003). IgA serum level was positive correlated with its IF grades (Neg-(+): p = 0.0001; (+)-(++): p = 0.022; Neg-(++): p = 2.01E-10). After matching comparison among C3 groups, C3 Neg. group and C3 ++ group had difference (*p = 0.017). C4 had all negative IF expression in all pathological groups. In IgAN subjects, there were statistical differences of serum C3 levels between its pathological Neg and positive (+) group(p = 0.026), and serum IgA levels showed difference between IgA pathological positive(+) and (++)(p = 0.007). In MN subjects, sIgG levels showed difference between IgG pathological IF grade positive (+) and (++)(p = 0.044); serum C3 levels showed difference between C3 pathological IF grade Neg and positive(+)(p = 0.005); and serum IgA levels showed difference between Neg and positive(+)(p = 0.040). In IgAN, eGFR showed serum IgA levels had significant differences among groups (p = 0.007) and had increasing trend with enhanced its IF grades(Ptrend = 0.016). There were also difference between IgG group Neg and positive (+) (p = 0.005, Ptrend = 0.007) in IgAN. In MN, serum IgG levels had significant differences among IF groups (p = 0.034) and had decreasing trend with its enhanced IF grades (Ptrend = 0.014). Serum C3 concentrations also were found distinctive among IF groups (p = 0.016) and had in inverse correlation with its enhanced IF grades (Ptrend = 0.004). Discussion Our research cross contrasts several immunoprotein IF intensities and relevant serum levels in three kinds of primary glomerular nephritis, and finally acquired helpful results for understanding the relationships between pathological presentation and serological presentation of immunoproteins in kidney diseases. Furthermore, this pilot study is offering a possible method for the analysis of combination of pathology and serology. Conclusion Different pathological types of nephritis presented different expression patterns of immunoglobulin and complement, especially IgA and IgG, which suggested different pathogenesis involved in the development of IgAN and MN. Furthermore, either in tissue or in serum, increased IgA level was closely related with renal function in all of the patients.http://link.springer.com/article/10.1186/s12865-018-0254-zImmunoglobulin A nephropathyMembranous nephropathyMinimal change diseaseImmunoglobulinComplement
spellingShingle Jin Dong
Tianhao Peng
Jing Gao
Xingwang Jia
Guangtao Yan
Yong Wang
A pilot and comparative study between pathological and serological levels of immunoglobulin and complement among three kinds of primary glomerulonephritis
BMC Immunology
Immunoglobulin A nephropathy
Membranous nephropathy
Minimal change disease
Immunoglobulin
Complement
title A pilot and comparative study between pathological and serological levels of immunoglobulin and complement among three kinds of primary glomerulonephritis
title_full A pilot and comparative study between pathological and serological levels of immunoglobulin and complement among three kinds of primary glomerulonephritis
title_fullStr A pilot and comparative study between pathological and serological levels of immunoglobulin and complement among three kinds of primary glomerulonephritis
title_full_unstemmed A pilot and comparative study between pathological and serological levels of immunoglobulin and complement among three kinds of primary glomerulonephritis
title_short A pilot and comparative study between pathological and serological levels of immunoglobulin and complement among three kinds of primary glomerulonephritis
title_sort pilot and comparative study between pathological and serological levels of immunoglobulin and complement among three kinds of primary glomerulonephritis
topic Immunoglobulin A nephropathy
Membranous nephropathy
Minimal change disease
Immunoglobulin
Complement
url http://link.springer.com/article/10.1186/s12865-018-0254-z
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