Dong J, et al. - In this pilot study, researchers studied the association of immunofluorescence (IF) intensity and serum values of immunoglobulin and complement in immunoglobulin A nephropathy (IgAN), membranous nephropathy (MN) and minimal-change disease (MCD) by integrating histopathological indicators into serum parameters. They also screened and investigated effective indicators in these 3 disease entities. They found expression patterns of immunoglobulin and complement differed in different pathological types of nephritis, this was especially true for IgA (immunoglobulin A) and IgG (immunoglobulin G); this suggested the implication of different pathogenesis in the development of IgAN and MN. Furthermore, all patients demonstrated a close association between increased IgA level, either in tissue or in serum, and renal function.

Methods

• This study included 236 cases with IgAN, MN or MCD.
• In these cases, researchers retrospectively analyzed renal tissue immunofluorescence (IF) intensity grades and serum levels of immunoglobulin and complements (IgG, IgA, IgM, C3 and C4).
• Groups of IF grades included negative (-), positive (+) or strong positive (++) with both high and low magnification of microscope.
• Among the groups, assessments of other serum indicators such as urea nitrogen (BUN), creatinine (Crea) and estimated glomerular filtration rate (eGFR) were also performed.

Results

• Among IgAN, MN and MCD groups, difference in IgA, IgG and C3 IF intensity grades was evident (p = 9.82E-43, 4.60E-39, 7.45E-15, respectively).
• Three groups had different serum values of BUN, Crea, eGFR, IgG, IgA, IgM and C4 (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).
• With respect to eGFR, they noted a trend towards its decline with enhanced IgA IF positive grades (p=8.99E-4); with both enhanced IgA and IgG IF intensity grades, Crea showed trends to decrease (p=2.06E-6, 2.94E-5, respectively).
• An inverse correlation of serum IgA levels with eGFR (r = - 0.216, p=0.001) and correlation with Crea levels (r = 0.189, p=0.004) was seen in all subjects; 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).
• An inverse correlation was observed, of IgG serum level with its IF grades (p=3.54E-5, p=7.08E-6, respectively); they found C3 serum levels had significantly difference between Neg and positive (+) group (p=0.0003).
• Findings revealed a positive correlation of IgA serum level with its IF grades (Neg-(+): p=0.0001; (+)-(++): p=0.022; Neg-(++): p=2.01E-10).
• Difference was observed in C3 Neg. group and C3 ++ group (*p=0.017) after matching comparison among C3 groups.
• C4 had all negative IF expression in all pathological groups.
• The pathological Neg and positive (+) group of IgAN subjects demonstrated statistical differences of serum C3 levels (p=0.026), and difference was also noted in serum IgA levels between IgA pathological positive(+) and (++)(p=0.007).
• Difference between IgG pathological IF grade positive (+) and (++)(p=0.044) was shown by sIgG levels in MN subjects; they found serum C3 levels demonstrated variance between C3 pathological IF grade Neg and positive(+)(p=0.005); and serum IgA levels showed difference between Neg and positive(+)(p=0.040).
• They observed that significant differences in serum IgA levels were demonstrated by eGFR among groups (p=0.007) and serum IgA levels had increasing trend with enhanced its IF grades(P_trend=0.016).
• In IgAN, they also noted difference between IgG group Neg and positive (+) (p=0.005, P_trend= 0.007).
• Findings revealed serum IgG levels had significant differences among IF groups (p=0.034) and had decreasing trend with its enhanced IF grades (P_trend=0.014) in MN.
• Among IF groups, distinctive serum C3 concentrations were found (p=0.016); these had in inverse correlation with its enhanced IF grades (P_trend=0.004).