Diagnostic value of pathological features of atypical membranous nephropathy

Objective To evaluate the diagnostic value of pathological features of atypical membranous nephropathy (AMN). Methods Ninety-one patients with AMN diagnosed by renal biopsy during 2011 and 2017 were enrolled in this study. On the basis of M-type phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A protein (THSD7A) by immunohistochemistry, patients were divided into AMN group (25 cases without PLA2R and THSD7A) and idiopathic membranous nephropathy (IMN) group (66 cases with positive PLA2R or THSD7A). The results of immunofluorescence (IF), light microscopy (LM) and electron microscopy (EM) of these two groups were compared, and the parameters with statistical difference were screened out in order to assess their value in the diagnosis of AMN in fourfold table. Results IF results showed that in AMN group the proportions of IgG deposition on capillary wall and mesangial area as well as positive other IgG subclasses and complement C1q but negative IgG4 were significantly higher than those in IMN group (respectively, 56.0% vs 12.1%, 44.0% vs 0, both P＜0.05). Their diagnostic specificities for AMN were 87.9% and 100.0%, respectively. However, the positive rates of IgG accompanied with IgA and/or IgM, predominant IgG4 with other IgG subclasses and complement C1q in two groups were not significantly different (all P＞0.05). LM results showed that the proportions of false double track sign on basement membrane and fuchsinophilic proteins under epithelium, endothelium, basement membrane and mesangial region in AMN group were significantly higher than those in IMN group (respectively, 36.0% vs 0, 44.0% vs 1.5%, both P＜0.05). Their diagnostic specificities for AMN were 100.0% and 98.5%, respectively. However, the scores of mesangial cell proliferation of these two groups showed no significantly difference (P＞0.05). EM results showed that the rate of endothelial electron dense deposits in AMN group was significantly higher than that in IMN group (36.0% vs 1.5%, P＜0.05), and its diagnostic specificity for AMN was 98.5%. Conclusions IgG deposition on both capillary wall and mesangial area, positive other IgG subclasses and C1q with negative IgG4, false-double contour sign, multi-site fuchsinophilic deposits and endothelial electron dense deposits may help for the AMN diagnosis in the absence of PLA2R and THSD7A related data.     

Clinical-pathologic features and outcomes of IgA nephropathy patients with IgM deposition

Objective To determine the correlation of IgM deposition with clinic-pathological features and outcomes of IgA nephropathy patients. Methods A total of 1060 patients, who were diagnosed as IgA nephropathy by renal biopsies between 2001 and 2007 in Guangxing Hospital were enrolled. According to immunofluorescent test, patients were divided into patients with mesangial IgM deposition and patients without IgM deposition. Renal survival curves were assessed by Kaplan-Meier method. The effect of IgM deposition on outcomes of IgA nephropathy patients was examined by univariate and multivariable Cox proportional-hazards regression. Results Among 1060 IgA nephropathy patients, there were 750 patients with IgM deposition and 310 patients without IgM deposition. (1) Urinary protein and uric acid in patients with IgM deposition were significantly higher than those in patients without IgM deposition (all P＜0.05). Other clinical indicators shown no statistical difference (all P＞0.05). Moreover, IgM deposition patients had higher serum IgA, serum IgG and serum IgM (all P＜0.05). (2) In pathological indicators, IgM deposition patients had more segmented sclerosis or adhesions (S1 of Oxford classification), activity lesions as inflammatory cell infiltration and mesangial proliferation, and chronic pathological changes as tubular atrophy, segmented glomerular damage than patients without IgM deposition (all P＜0.05). (3) All patients were followed-up for a median of 89.7(61.8, 113.4) months, Kaplan-Meier analysis revealed that kidney survival rate was significantly lower in IgM deposition patients compared with patients without IgM deposition (Log-rank χ2=4.95, P=0.026). In a univariate Cox hazards regression mode, IgM deposition was a risk factor for poor prognosis of IgA nephropathy patients (HR=1.597, 95%CI 1.053-2.422, P=0.027). However, in a multivariable Cox analysis, IgM deposition shown no influence on outcomes of IgA nephropathy patients (HR=1.409, 95%CI 0.921-2.156, P=0.114). Conclusions IgA nephropathy patients with IgM deposition have higher urinary protein, and more serious pathological damage and immune fluorescence deposition. IgM deposition affects renal survival of IgA nephropathy, while IgM deposition is not an independent risk factor for prognosis of IgA nephropathy.     

Clinical and pathological features of young patients with idiopathic membranous nephropathy in 20 cases

Objective To investigate the clinical and pathological features of idiopathic membranous nephropathy (IMN) in young patients. Methods Clinical data of 20 young patients, 16 to 44 years, who were diagnosed as IMN admitted to the Zhejiang Provincial People's Hospital from January 2013 to December 2014 were retrospectively analyzed, comparing to 55 mid-aged patients who were diagnosed as IMN during the same period in the hospital. Clinical and pathological features of above mentioned patients were analyzed. Results Young patients with IMN accounted for 26.7% of IMN patients. Compared to mid-aged patients, young patients with IMN had lower proportion of hypertension (P=0.003), lower blood glucose level (P=0.010), higher estimated glomerular filtration rate (eGFR) and low-density lipoprotein (LDL) (P=0.012, P=0.038), and lower levels of T3 and T4 (P=0.030, P=0.034). Furthermore, there were less sclerosis glomeruli (P＜0.001), hyaline change of arteriole (P=0.040) and arteriolar wall thickening (P＜0.0001), lower positive ratios of IgA (P=0.008), and more without renal tubulointerstitial lesions (P=0.018) in young patients. There were no statistically significant differences between these two groups in other index. Conclusions Compared to mid-aged patients, young patients with IMN have better blood pressure and blood glucose level, higher glomerular filtration rate and LDL. Moreover, thyroid function is significantly affected, meanwhile the lesions of glomerular, interstitial and vascular are mild in young patients.     

三种实验性IgA肾病模型的比较

目的探讨建立一种理想的IgA肾病（IgAN）动物模型方法。方法分别采用葡聚糖G200、大肠杆菌外膜蛋白和金葡菌的细胞膜20肽抗原决定簇诱导小鼠IgA肾病模型。用分子生物学和病理学方法对3组IgAN模型小鼠进行鉴定和比较。结果（1）葡聚糖组尿蛋白增高，伴有血尿；免疫荧光显示部分肾小球大量IgA沉积；光镜下肾小球系膜细胞增多，肝和脾可见弥漫性的粉染物质沉积；电镜下肾小球系膜区少量低电子密度的致密沉积物，肝和脾可见淀粉丝样物质沉积。（2）大肠杆菌外膜蛋白组尿蛋白增高，伴有血尿；免疫荧光显示肾小球有少量IgA沉积；光镜下肾小球系膜细胞轻度增多，间质炎细胞浸润明显；电镜下肾小球系膜区无电子致密沉积物。（3）金葡菌细胞膜20肽抗原决定簇组尿蛋白增高，伴有血尿；免疫荧光显示多数肾小球均可见大量IgA沉积；光镜下肾小球系膜细胞增多，伴系膜基质轻度增生；电镜下肾小球系膜区和基底膜的内皮细胞下可见高电子密度的致密沉积物。结论金葡菌细胞膜20肽抗原决定簇组诱导的IgAN模型从临床表现和病理学变化与人IgAN极其相似，是3种IgAN模型中最理想的IgAN模型。     

Clinical significance of phospholipase A2 receptor 1 in patients with idiopathic membranous nephropathy

Objective To explore the role of phospholipase A2 receptor 1 (PLA2R1) in the diagnosis, differential diagnosis and evaluation of idiopathic membranous nephropathy (IMN) in adult patients. Methods A total of 242 renal disease patients diagnosed by renal biopsy from March 2015 to January 2016 were enrolled, consisting of 90 IMN, 20 secondary membranous nephropathy (SMN), 82 IgA nephropathy (IgAN), 30 minimal changed disease (MCD), 16 focal segmental glomerulosclerosis (FSGS) and 4 membranoproliferative glomerulonephritis (MPGN). Their clinical data including age, sex, serum creatinine (Scr), serum albumin and 24 h urinary protein were collected. Serum PLA2R1 was measured by enzyme linked immunosorbent assay. PLA2R and IgG subclasses in glomeruli were detected by indirect immunofluorescence assay. The positive rate of serum PLA2R1 among those groups and its correlation with clinical-pathological parameters were analyzed. Results Compared with IMN patients, SMN, MCD and FSGS patients were younger (all P＜0.01); IgAN patients were younger and had higher serum albumin and lower 24 h proteinuria (all P＜0.001); MPGN patients had higher Scr (all P＜0.01). The positive rate of serum PLA2R1 was 75.6% in IMN patients, while it was 0.0% in non-IMN patients. The distribution between serum PLA2R1 and pathological diagnosis had difference (P＜0.001), their positive coincidence rate was 100%, negative coincidence rate was 87.4%, total coincidence rate was 90.9% and their consistency was well (Kappa=0.795, P＜0.001). Among IgG subtype comparisons between IMN patients and SMN patients in the glomeruli, only moderate or more positive IgG4 had statistical differences (82.2% vs 5.0%, P＜0.001); the positive rate of glomerular PLA2R1 was 41.1% in IMN patients, higher than 10.0% in SMN patients (P=0.009); positive PLA2R1 with moderate or more positive IgG4 in glomeruli in IMN patients was more than that in SMN patients (40.0% vs 0.0%, P＜0.001), which could improve the diagnostic specificity of IMN. In IMN patients serum PLA2R1 and glomerular PLA2R1 had statistical differences (P＜0.001). Spearman rank correlation analysis showed that serum PLA2R1 of IMN patients positively correlated with 24 h proteinuria (r=0.315, P=0.002), negatively correlated with serum albumin (r=-0.228, P=0.030) and didn't correlate with Scr (r=0.199, P=0.059). Conclusions Serum PLA2R can be used as the specific indicator for diagnosis, differential diagnosis of IMN and to reflect the severity of IMN in patients.     

Clinicopathological features of antineutrophil cytoplasmic antibodies associated vasculitis with glomerular IgA deposits

Objective To investigate the clinical manifestations, renal pathology and prognosis of antineutrophil cytoplasmic antibody-associated small-vessel vasculitis (AAV) accompanied with renal glomerular IgA deposition. Methods A retrospective analysis was performed at the First Affiliated Hospital of Zhejiang University College of Medicine. Patients diagnosed with AAV associated renal injury by renal biopsy from February 2004 to February 2017 were enrolled. Patients with antiglomerular basement membrane antibody-mediated nephritis, systemic lupus erythematosus nephritis, Henoch Schonlein purpura nephritis, hepatitis B virus associated nephritis and other known etiology were excluded. According to immunofluorescence examination, the patients were divided into IgA deposition group and pauci-immune complex deposition group. The differences in clinical manifestation, pathological features and prognosis were compared between groups. Results A total of 150 AAV cases were included, among which 25 cases were with IgA deposition and 125 cases with pauci-immune complex deposition. The level of serum albumin in IgA deposition group was higher than that in pauci-immune complex deposition group [(35.0±6.2) g/L vs (32.6±5.3) g/L, P=0.049], but the titer of MPO-ANCA was lower [24.8(10.4, 71.8) U/ml vs 63.0(21.9, 100.0) U/ml, P=0.044] in IgA deposition group. There was no significant difference between two groups in other laboratory indexes and renal pathological findings. The median follow-up time was 15.2 months in IgA deposition group and 8.9 months in pauci immune complex deposition group. During the follow-up there were 8 patients (32.0%) in IgA deposition group and 29 patients (23.2%) in pauci immune complex deposition group on maintaining dialysis; 2 patients (8.0%) in IgA deposition group and 7 patients (5.6%) in pauci immune complex deposition group died. There was no significant difference between two groups in patients' outcomes. Conclusions AAV patients with glomerular IgA deposition and AAV patients with typical glomerular immunoglobulin complex deposition are similar as regards clinical appearance and prognosis.     

Incidental mesangial IgA deposition in minimal change nephrotic syndrome(MCNS)

The frequency of incidental mesangial IgA deposition and its clinicopathological features were investigated in patients with minimal change nephrotic syndrome(MCNS). Mesangial IgA deposition was present in 15/63 patients(23.8%), and co-deposition of IgA and C3 was present in 10/63 patients(15.9%). The serum IgA concentration was significantly higher in IgA(+) patients than in IgA(-) patients(341 +/- 79 mg/dl vs. 252 +/- 99 mg/dl, p = 0.034). The urinary red blood cell count tended to be higher in IgA(+) patients than in IgA(-) patients (12.8 +/- 24.9 vs. 5.0 +/- 7.9 counts/HPF, p = 0.58). Histologically, no significant differences were observed between IgA(+) and IgA(-) patients. After steroid treatment. 14 patients with mesangial IgA deposition showed complete remission and one patient had persistent proteinuria. The microhematuria also disappeared after steroid treatment in 13/15 patients (86.7%), although it reappeared in 6/13 patients(46%) during reduction of steroid administration. The present study indicated that the incidental mesangial IgA deposition was frequently observed in MCNS patients(23.8%). The phenomenon of mesangial IgA deposition was related to the higher concentration of serum IgA. However, no influence of mesangial IgA deposition in MCNS patients was found on the post-treatment amount of proteinuria, renal function and clinical outcome of MCNS.     

Autoantibodies against glomerular mesangial cells and their target antigens in lupus nephritis

Mesangial proliferation and deposition of immunoglobulins and complement components within glomerular mesangium was one of the important pathological features of lupus nephritis. Autoantibodies against human mesangial cells could be detected in the sera of patients with IgA nephropathy (IgAN) and Henoch-Sch?enlein nephritis. We speculated that autoantibodies against human glomerular mesangial cells might play a role in the development of lupus nephritis. OBJECTIVE: To screen autoantibodies against human glomerular mesangial cells in sera from patients with lupus nephritis and to identify their target antigens. METHODS: Sera were collected from 96 patients with lupus nephritis as well as 25 patients with IgAN and 20 patients with idiopathic membranous nephropathy (IMN). Cell lysates of in vitro cultured human glomerular mesangial cells were used as antigens in Western-blot analysis to detect autoantibodies against human mesangial cells in sera from patients with lupus nephritis as well as IgAN and IMN. The clinical and pathological significance of the autoantibodies were further investigated. RESULTS: Autoantibodies against human mesangial cells could be detected in 94/96 (97.9%) of the sera from patients with lupus nephritis in Western-blot analysis. Twelve protein bands could be blotted by the sera from patients with lupus nephritis. The prevalence of autoantibodies against human mesangial cells in IgAN was 14/25 (56.0%) and only seven protein bands could be blotted. Five autoantibodies (anti-18, 24, 36, 46, and 91 kD) could be detected only in sera from patients with lupus nephritis. In patients with lupus nephritis, some autoantibodies might have some relationship with gender, hematuria, ANA, anti-dsDNA or anti-ENA antibodies. CONCLUSIONS: There are autoantibodies directly against heterogeneous antigens of human glomerular mesangial cells in sera from patients with lupus nephritis, and some of them might be associated with different clinical manifestations.     

Relationship between renal phospholipase A2 receptor expression and clinical characteristics,prognosis in idiopathic membranous nephropathy patients

Objective To explore the relationship of phospholipase A2 receptor (PLA2R) expression in renal tissue with clinical characteristics, prognosis of idiopathic membranous nephropathy(IMN) patients. Methods 134 patients diagnosed as nephropathy proven by biopsy was selected as subjects of this research, including 98 patients with IMN patients, 10 patients with secondary membranous nephropathy and 26 patients with other renal glomerular diseases. The expression of PLA2R antigen in renal tissue was detected by immuno-fluorescence chemistry staining. Results The positive rate of renal PLA2R expression in IMN patients was higher than that in SMN patients (91.84% vs 40.00%, P＜0.01), whereas there is no expression in other glomerular diseases. The PLA2R negative group were mainly stage I membranous nephropathy, and positive group was mainly in stage II. The distribution of pathological stage between the two groups was statistically significant (P＜0.01). Compared with the positive group, the negative group was manifested with higher eGFR[(115.91±23.32) ml?min-1?(1.73 m2)-1 vs (94.06±27.38) ml?min-1?(1.73 m2)-1, P=0.031], associated with the higher 12-month complete remission rate (87.50% vs 44.07%, P=0.021). Conclusions The expression of PLA2R antigen in renal tissue plays an important role in the diagnosis, disease evaluation and prognosis of IMN. The negative PLA2R in kidney tissue of IMN may indicate a good clinical prognosis.     

Incidence of latent mesangial IgA deposition in renal allograft donors in Japan

BACKGROUND: Mesangial immunoglobulin A (IgA) deposition is incidentally encountered in asymptomatic individuals, but its precise frequency and significance had not been clarified. The background of the latent IgA deposition is related to the epidemiology and pathogenesis of IgA nephropathy. METHODS: Zero-hour allograft biopsies were performed in 510 renal transplantations (446 living donors, and 64 cadaveric donors) at the Kidney Center of Tokyo Women's Medical University. Mesangial IgA and C3 deposition were analyzed immunohistochemically, and the frequency and clinicopathologic features of mesangial IgA deposition were investigated. RESULTS: Mesangial IgA deposition was present in 82 (16.1%) of the total 510 allografts with no statistical difference between living donors (72/446, 16.1%) and cadaveric donors (10/64, 15.6%) or between blood-related donors (66/392, 16.8%) and nonblood-related donors (16/110, 14.5%). Mesangial C3 deposition was present in 16 (19.5%) of the 82 allografts with mesangial IgA deposition. The grade of hematuria in IgA(+) donors was significantly higher than IgA(-) donors (1.30 +/- 1.17 vs. 0.86 +/- 0.89, P = 0.025). Histologic investigation of IgA(+) allografts revealed the frequency of mesangioproliferative glomerulonephritis (PGN) was significantly higher in IgA(+)/C3(+) allografts (8/16, 50%) than in IgA(+)/C3(-) allografts (11/66, 16.7%) (P = 0.0084). Moreover, the number of infiltrated macrophages to glomerulus (cells/glomerular cross section) was significantly higher in the IgA(+)/C3(+) allografts than in IgA(+)/C3(-), IgA(-)/C3(+) and IgA(-)/C3(-) allografts (1.10 +/- 0.62 vs. 0.61 +/- 0.42, P = 0.0008; 0.47 +/- 0.34, P = 0.023; and 0.37 +/- 0.23, P = 0.002, respectively). CONCLUSION: The latent mesangial IgA deposition was a relatively common phenomenon in the healthy Japanese donors. This phenomenon was associated with mild degree of microhematuria, mesangial proliferation and glomerular macrophage infiltration in some of the affected individuals, especially with combined IgA and C3 deposition.     

Impact of mesangial IgA deposits in 14th‐post operative‐day routine renal allograft biopsies

SUMMARY: Three hundred fourteen 14th‐postoperative‐day routine renal allograft biopsies were evaluated together with clinical data. Out of 314 biopsies, mesangial IgA deposits were positive in 122 biopsies (39%). According to Banff classification, the rate of acute rejection was significantly lower in mesangial IgA deposit‐positive (IgA(+)) patients (7.4%) than in mesangial IgA deposit‐negative (IgA(‐)) patients (19.7%) on the 14th postoperative day. Thereafter, rate of biopsy‐proven and clinical acute rejection was continuously lower for up to 12 months in IgA(+) patients than in IgA(‐) patients. The detection rate of mesangial IgA deposits was significantly higher in human leucocyte antigen (HLA)‐well‐matched (HLA mismatch number was <3) patients than in HLA‐poorly matched (HLA mismatch number was ≥3) patients. In HLA‐well‐matched patients, the serum creatinine levels were significantly lower in IgA(+) patients than in IgA(‐) patients after 3 post‐transplant months and up to 1 post‐transplant year. Follow‐up (mean interval: 13 months) allograft biopsies were performed in 34 patients out of 122 IgA(+) patients. In the follow‐up biopsies, initially detected mesangial IgA deposits had disappeared in 22 patients (65%) out of 34 patients. Twelve patients (35%) still had mesangial IgA deposits, and all of them had clinical and pathological findings consistent with IgA nephropathy. Patients with continuous mesangial IgA deposits in the follow‐up biopsies had a better renal function at 1 year and a higher 5‐year graft survival rate compared with patients who lost the initially deposited IgA. The present study demonstrates that long‐lasting mesangial IgA deposits in renal transplants prevent allografts from acute rejection, which leads to better graft outcome.     

Anti -PLA2R autoantibodies in serum and IgG subclass deposits on glomeruli in undetermined atypical membranous nephropathy

ObjectiveTo investigate the characteristic of autoantibodies of M – type phospholipase A2 receptor (PLA2R) in serum and the glomerular IgG subclass deposits in undetermined atypical membranous nephropathy (MN) patients. MethodsFrom Feb 2004 to Nov 2011, 53 cases diagnosed as MN by kidney puncture biopsy in our hospital were included into the study. There were 20 undetermined atypical membranous nephropathy (UAMN), 20 idiopathic membranous nephropathy (IMN) and 13 secondary membranous nephropathy (SMN) which were composed of lupus membranous nephropathy (LMN) and HBV related membranous nephropathy (HBV-MN). Clinlical and pathological characteristics were analyzed. The autoantibodies of PLA2R in serum were detected and the glomerular IgG subclass deposits were observed. Results(1) The average age underwent renal biopsy was (37.9±3.8) years of UAMN, (50.1±3.0) years of IMN and (49.5±4.5) years of SMN. The difference in onset average age at disease was significant between UAMN and IMN (P＝0.0178). The female/male ratio (F/M) in UAMN, IMN and SMN was 0.8∶1, 0.7∶1 and 0.6∶1(P＞0.05). (2) Compared with SMN, the level of 24-hours urinary protein excretion (3.47 g vs 7.89 g, P＝0.023), the ratio of amount urinary protein patients (50.0% vs 84.6%, P＝0.043), the level of serum IgG [(8.40±3.58) g/L vs (10.09±4.69) g/L, P＝0.025] and the positive rate of ANA in serum (10.0% vs 53.8%, P＝0.006) in UAMN were all much lower. There were no significant statistical differences in serum albumin, serum creatinine, eGFR, positive rate of HBsAg, HBeAg or HCV, as well as the ratio of hypo - albuminemia and nephritic syndrome among the three groups. (3) IF positive rate of IgA, IgM and C1q in UAMN were all significantly higher than that in IMN (P＜0.01). There were no significant differences in IF positive rate of IgA, IgM, C1q, IgG and C3 between UAMN and SMN. The IF strength of IgA, IgG, IgM, C3 and C1q in UAMN showed no significant differences between UAMN and SMN. (4) The serum autoantibodies of PLA2R were only detected in 10 cases of IMN group (50%) with all the other cases negative. This detection rate of serum autoantibodies of PLA2R showed significant statistical differences among the three groups (P＜0.01), but no differences between UAMN and SMN (the detection rate in both groups were 0%). (5) IgG1 deposits was the dominant IgG on the glomeruli in UAMN group (40%), as well as in SMN group (76.9%). IgG4 deposits was the dominant IgG on the glomeruli in IMN group (60%). The positive rate of IgG1 and IgG3 in UAMN showed no significant statistical differences when compared with IMN or SMN. The positive rate of IgG2 in UAMN was significantly lower than in SMN（30.0% vs 69.2%, P＜0.05). The positive rate of IgG4 in UAMN was significantly lower than in IMN (20% vs 60%, P＜0.05). The positive rate of IgG1, IgG2 and IgG3 in SMN were all significantly higher than in IMN. ConclusionsNone of the UAMN group had autoantibodies of PLA2R in serum, and IgG1 deposits was the dominant IgG subclass on the glomeruli which indicated the similarity with the SMN group. At the same time, UAMN was significantly different from SMN in clinical manifestations.     

血清抗核抗体阳性的不典型膜性肾病与狼疮膜性肾病及特发性膜性肾病的临床病理比较

目的 探讨血清抗核抗体（ANA）阳性的不典型膜性肾病（AMN）与狼疮膜性肾病（LMN）、特发性膜性肾病（IMN）的关系，寻找对诊断LMN具有较高预测价值的临床和病理学指标。 方法 2003年1月至2006年12月期间在北京协和医院住院并行肾活检，临床、病理资料保存完整的患者为对象。分组：AMN组（n = 28）：血清ANA滴度≥1∶80，少于4条美国风湿病学会（ARA）修订的系统性红斑狼疮分类标准，病理呈肾小球基底膜病变伴系膜增生和（或）免疫荧光C1q阳性；IMN组（n = 100）；LMN组（n = 45）。回顾性分析各组病例的临床表现、病理学特点。应用免疫组化法，对各组部分病例肾活检组织行IgG亚型染色，半定量分析染色强度。对各组部分病例肾活检组织行免疫荧光双染色（IgG-TRITC，C3-FITC），用激光扫描共聚焦显微镜观察肾小球沉积的IgG和C3的空间分布。 结果 (1)AMN组起病年龄（38±17）岁，女∶男比为2.5∶1，介于LMN和IMN之间。3组起病年龄差异有统计学意义（P < 0.01），AMN组女∶男比高于IMN组（P = 0.017）。AMN组血液系统异常、血抗SSA抗体阳性百分比较高（21.4%、40.7%）。(2)AMN组系膜增生、系膜区及内皮下电子致密物出现的百分比高于IMN组（P < 0.01）。(3)AMN和LMN组肾小球IgG3沉积占优势的百分比分别为78.9%、73.9%；IMN组IgG4沉积占优势的百分比为61.1%，差异均有统计学意义（IMN组与AMN、LMN组比较, P < 0.01）。(4)IMN组常出现IgG和C3在上皮下的共沉积现象，而在AMN和LMN组中少见。(5)在鉴别LMN和IMN的指标中，敏感性较高的有肾小球IgG4不占优势（91.3%）；特异性较高的有内皮下电子致密物（100.0%）、血抗SSA抗体（95.5%）、肾小球IgG3占优势（94.4%）。 结论 AMN的临床表现与IMN类似，而各项病理学特点，尤其是肾小球IgG亚型沉积特点与LMN更为接近。它有可能是狼疮肾炎中较为隐匿的一个亚型。     

Long-term course of post-transplant mesangial IgA deposition: clinicopathologic study of nine cases

Abstract:  We conducted the present study to elucidate the fate of post-transplant mesangial IgA deposit under the long-term observation. Out of a total of 45 cases with post-transplant mesangial IgA deposition, nine cases with more than 4 yr of follow-up term were enrolled in this study, and clinicopathologic characteristics were described. The study included three men and six women with a mean age of 34.2 yr. The average observation time from the detection of mesangial IgA deposition was 6.1 yr. Three cases were categorized as recurrent IgA nephropathy, while six cases were classified into latent mesangial IgA deposition. One case with hypertension developed end-stage renal disease. The significant improvement in microscopic hematuria was observed in one recurrent IgA nephropathy case. Microscopic findings included mild mesangial stalk thickening in all but one case. IgA deposition demonstrated a significant decrease in three latent mesangial IgA deposition cases. No apparent reduction in dense deposit quantity was observed on electron microscopy. There was no association between clinicopathologic findings and the regimen of anti-immunosuppressive agents. This study showed the improvement of the disease activity did occur in both recurrent IgA nephropathy and latent mesangial IgA deposition. Further investigation of latent mesangial IgA deposition may present the important clue to the pathogenesis of IgA nephropathy.     

光镜无法鉴别的早期特发性膜性肾病与轻度系膜增生性肾炎临床病理特征对比分析

目的:比较光镜无法鉴别、经电镜诊断的早期特发性膜性肾病(IMN)与轻度系膜增生性肾炎(mild-MsPGN)临床病理特点。方法:收集2016年01月~2017年12月在我院经光镜诊断为mild-MsPGN及其中经电镜确诊为早期IMN患者的临床病理资料,回顾性分析两组患者的临床表现、实验室指标及病理特征。结果:(1)Mild-MsPGN组临床表现以慢性肾炎为主、早期IMN组以肾病综合征为主(P=0.009),两组患者平均血压、肾功、血脂、凝血指标比较差异无统计学意义(P>0.05);(2)免疫荧光检测,早期IMN组可见Ig G沿毛细血管壁呈颗粒状沉积,mild-MsPGN组IgG均为阴性;余免疫荧光指标包括IgM、IgA、C3、C1q及血清免疫学指标两组差异均无统计学意义(P>0.05);(3)血清M型磷脂酶A2受体(PLA2R)抗体阳性率,早期IMN组仅22.73%、mild-MsPGN组为0%;(4)肾小管间质损伤指数,早期IMN组(1.18±0.50)低于mild-MsPGN组(1.51±0.78),P=0.036;(5)电镜下肾小球基底膜(GBM)厚度,早期IMN组(569.2±134.7)nm高于mild-MsPGN组(372.6±82.8)nm,P<0.001;早期IMN组足突广泛融合及足细胞弥漫空泡变性比例均较mild-MsPGN组高(分别为P<0.001和P=0.007)。结论:(1)光镜下mild-MsPGN的病例,电镜具有重要诊断意义,其更值得电镜下仔细鉴别相关病变;(2)活动性IMN中血清PLA2R抗体对临床诊断的阳性反应可能慢于电镜形态学表现。     

Defective in vivo Fc- and C3b-receptor function in IgA nephropathy

Reticuloendothelial function was assessed in 17 patients with IgA nephropathy, using 99Tc-labeled autologous erythrocytes coated with either C3B or IgG. Results were compared with clearances in 14 normal control subjects and with a group of 14 patients with idiopathic mesangial proliferative glomerulonephritis without IgA deposition. The half-life of IgG-coated red cells in the IgA group was 69.8 +/- 32.5 minutes (control 42.2 +/- 9.0 minutes, P = 0.001). The half-life in the non-IgA mesangial proliferative group, 77.9 +/- 31.3 minutes, was not significantly different from that of the IgA patients. Clearance of C3b-coated cells, expressed as the percentage of cells cleared at 30 minutes, was 7.1% +/- 2.6% in the IgA patients, compared with 16.0% +/- 3.2% in control subjects (P less than 0.001) and 13.8% +/- 7.5% in the non-IgA mesangial proliferative group (NS). No statistical correlation was found between clearance results in individual patients and age, sex, weight, serum creatinine, or the severity of disease on clinical and pathological criteria. The severity of the defect in Fc- and C3b-receptor dependent clearances were not statistically correlated in individual patients.     

Autoantibodies Against Glomerular Mesangial Cells and Their Target Antigens in Lupus Nephritis

Mesangial proliferation and deposition of immunoglobulins and complement components within glomerular mesangium was one of the important pathological features of lupus nephritis. Autoantibodies against human mesangial cells could be detected in the sera of patients with IgA nephropathy (IgAN) and Henoch-Schöenlein nephritis. We speculated that autoantibodies against human glomerular mesangial cells might play a role in the development of lupus nephritis. Objective. To screen autoantibodies against human glomerular mesangial cells in sera from patients with lupus nephritis and to identify their target antigens. Methods. Sera were collected from 96 patients with lupus nephritis as well as 25 patients with IgAN and 20 patients with idiopathic membranous nephropathy (IMN). Cell lysates of in vitro cultured human glomerular mesangial cells were used as antigens in Western-blot analysis to detect autoantibodies against human mesangial cells in sera from patients with lupus nephritis as well as IgAN and IMN. The clinical and pathological significance of the autoantibodies were further investigated. Results. Autoantibodies against human mesangial cells could be detected in 94/96 (97.9%) of the sera from patients with lupus nephritis in Western-blot analysis. Twelve protein bands could be blotted by the sera from patients with lupus nephritis. The prevalence of autoantibodies against human mesangial cells in IgAN was 14/25 (56.0%) and only seven protein bands could be blotted. Five autoantibodies (anti-18, 24, 36, 46, and 91 kD) could be detected only in sera from patients with lupus nephritis. In patients with lupus nephritis, some autoantibodies might have some relationship with gender, hematuria, ANA, anti-dsDNA or anti-ENA antibodies. Conclusions. There are autoantibodies directly against heterogeneous antigens of human glomerular mesangial cells in sera from patients with lupus nephritis, and some of them might be associated with different clinical manifestations.     

IgA肾病肾病综合征临床病理特点及肾脏病理危险因素

目的：探讨IgA肾病肾病综合征患者临床病理特点及肾脏病理损害的危险因素。方法：选择1987年～2006年经肾活检确诊IgA肾病并表现为肾病综合征的患者118例，分析其临床病理特点，按肾脏病变轻重分为A组（n=34，包括Lee氏分级Ⅰ级、Ⅱ级）、B组（n=84，Ⅲ、Ⅳ、Ⅴ级），比较两组临床指标，并多因素分析影响肾脏病理损害的危险因素。结果：A、B两组高血压分别占11．8％ vs 63．1％；肾衰竭分别占15％ vs 41．7％；A、B两组尿蛋白≥6g／24h者分别占58．8％ vs 32．1％；尿红细胞满视野分别为14．7％ vs 50％。A组高血压、肾衰竭、镜下尿红细胞满视野发生率显著低于B组（P〈0．01），尿蛋白≥6g／24h发生率显著高于B组（P〈0．01）。A组平均动脉压、血肌酐明显低于B组（P〈0．01）；而尿蛋白定量、血红蛋白显著高于B组（P〈0．05）。多因素分析显示IgA肾病肾病综合征患者肾脏病理损害重的危险因素有平均动脉压、尿蛋白〈6g／24h、镜下尿RBC〉5．0×10^7／L（0R值分别为1．048，3．227，6．578；P值分别为0．034，0．047，0．002），血红蛋白是保护性因素（OR=0.723，P=0．035）。随着平均动脉压的升高、血红蛋白的降低、镜下尿红细胞数的增多，肾脏病理损害程度加重（P〈0．01）。结论：IgA肾病肾病综合征患者临床、病理表现存在差异，高血压、血红蛋白水平、24h尿蛋白排泄量、镜下尿红细胞程度有助于判断肾脏病理损害轻重。     

青少年特发性膜性肾病的临床和病理特点及其转归影响因素

目的分析青少年特发性膜性肾病(IMN)的临床和病理特征、治疗及预后。 方法回顾性分析2011年1月1日至2018年4月30日在解放军总医院肾脏病科经肾活检确诊的164例13~24岁青少年IMN患者的基本资料、实验室检查、肾活检病理、治疗方案等资料。患者分为少年组(13~18岁)60例,青年组(19~24岁)104例,以肾活检时间为起点随访6~24个月,分析不同药物治疗的有效性及预后。 结果患者的男女比例约为1.6∶1;少年组的血尿发生率(P＝0.002)和eGFR(P＝0.002)高于青年组,而IgA(P＝0.017)和IgG(P＝0.050)水平则低于青年组。两组的临床表现均以肾病综合征为主,肾脏病理以膜性肾病Ⅱ期最多见。少年组和青年组的血清磷脂酶A2受体(PLA2R)抗体阳性率分别为44.4%和40%。平均随访时间8.5(6,24)月,两组使用他克莫司和(或)糖皮质激素治疗IMN的总缓解率均为75%。少年组和青年组的24个月总缓解率分别为85.7%和96%(χ²＝1.303,P＝0.254),而24个月完全缓解率则分别为61.5%和79.2%(χ²＝1.329,P＝0.254)。少年组及青年组均无患者进展至终末期肾病(ESRD)。单因素Cox回归分析显示,血尿和低IgG血症(<4.0 g/L)预示IMN患者较低的24个月总缓解率。多因素Cox回归分析发现,血尿(HR＝0.345,95%CI: 0.035~0.188,P＝0.005)和IgG<4.0 g/L(HR＝0.278,95%CI: 0.034~0.434,P＝0.023)均为24个月总缓解率的独立危险因素,而且IgG<4.0 g/L(HR＝3.538,95%CI: 1.193~10.499,P＝0.028)还是24个月完全缓解率的独立危险因素。接受者操作特征(ROC)曲线下面积(AUC)也证实,IgG<3.48 g/L(AUC＝0.765,特异性69.4%,灵敏度88.7%,P＝0.001)是预测24个月不缓解的最佳临界点。 结论少年组IMN患者的临床表现较青年组严重;随访24个月时青少年IMN患者的转归良好;血尿和低IgG血症是青少年IMN缓解率的独立危险因素。     

Prevalence of idiopathic membranous nephropathy and clinicopathologic correlation with serum anti-PLA2R antibody in a single center

Objective To conduct a single-center retrospective analysis on the distribution characteristics and prevalence of idiopathic membranous nephropathy (IMN) patients diagnosed with pathology for the past 16 years, to investigate diagnostic and differential diagnostic value of serum anti-phospholipase A2 receptor antibodies (PLA2R-Ab), and to evaluate the correlation between PLA2R-Ab and clinical disease activity. Methods (1) 6996 biopsy-proven primary glomerular nephropathy (PGN) patients, including 1567 IMN cases, admitted to the First Affiliated Hospital of Xi'an Jiaotong University from January 2000 to December 2015 were involved. Demographics and pathological type were gathered from all patients. (2) 433 cases receiving renal biopsy and testing PLA2R-Ab from June 2015 to December 2015 were involved, with their clinical and laboratorial data being collected. During the period patients' follow-up time, therapeutic schedule and laboratory results were recorded. Results (1) IMN accounted for 22.4% of primary glomerular disease, and patients above 40 years old accounted for more than 60% of the IMN. (2) The sensitivity and specificity of serological PLA2R-Ab were 58.1%(95%CI 47.0%-68.5%) and 98.6%(95%CI 95.6%-99.6%) respectively. PLA2R-Ab positive rate was affected by immunosuppression therapy. (3) The PLA2R-Ab titers wasn't correlated with 24-hour urinary protein (r=-0.017, P=0.887), serum albumin (r=-0.072, P=0.549) and urinary red blood cell count (r=-0.030, P=0.802). There was no difference between PLA2R-Ab positive positive and PLA2R-Ab negative on proportion of IMN pathological stage I-II (P＞0.05). Thirteen cases of patients with PLA2R-Ab positive were all prescribed glucocorticoid combined with immunosuppressant. After (2.21±1.09) months, the decrease of PLA2R-Ab titers was in accordance with 24-hour urinary protein quantity descending and serum albumin ascending (P＜0.05). Conclusions The incidence of IMN increase year by year, especially in the mid-aged and the elderly. Serum PLA2R-Ab correlates not with IMN pathological stage, but with the development of IMN. Monitoring PLA2R-Ab titers individually may access the efficiency of treatment.