肾小管间质损害在IgA肾病中的临床意义

目的：探讨肾小管间质损（TIL）在IgA肾病（IgAN）中的临床意义。方法：分析609例IgAN患者的临床与病理资料。结果：肾小管间质损害情况,肾小管间质损害轻度占47．1％,中度者占21．7％,重度者占16．6％,无肾小管间质损害者仅占14．6％。肾小管间质损害与临床指标的关系;随着肾小管间质损害程度的加重。IgAN患者的病情亦逐渐加重,表现为知血压升高,尿蛋白定量增加,血清白蛋白下降及肾功能减退。肾小管间质损害与病理参数的关系。血管损害、肾小球总体损害、系膜增殖程度及球性硬化的积分随着肾小管间质损害程度的加重逐渐增高,反之,随着肾小球和血管病变的加重,肾小管间质损害程度亦相应加重,结论：肾小管间质损害在IgAN患者病理改变中广泛存在,并随其损害程度的加重,IgAN患者的病情亦逐渐加重,肾小管间质损害可能是决定IgAN预后不良的关键因素之,且其与肾小球及血管病程度均呈平行关系,从而提示肾小管间质害与肾小球和血管的病变有直接的关系。     

Th1/Th2平衡关系与IgA肾病临床、病理表现的相关性分析

目的探讨辅助性T（Th）1/Th2细胞平衡与IgA肾病（IgAN）临床、肾脏病理表现的相关性。方法采用流式细胞术检测40例IgAN患者与20例健康人对照组外周血Th1、Th2值;收集IgAN患者慢性扁桃体炎史和反复发作性肉眼血尿史,血清胆固醇（Tch）、三酰甘油（TG）、IgG、IgA、内生肌酐清除率（Ccr）,24 h尿蛋白及肾脏病理表现;并了解IgAN患者以上情况与Th1/Th2比例的相关性。结果 IgAN患者外周血中Th2细胞比例为（1.77±0.90）%,较健康对照组的（1.18±0.15）%升高（P〈0.01）。慢性扁桃体炎对Th1/Th2比例无明显影响;有反复发作性肉眼血尿的IgAN患者Th1细胞比例（8.50±4.68）%及Th1/Th2值（4.10±2.01）均较无反复发作性肉眼血尿IgAN患者高（P〈0.05）,24 h尿蛋白定量大于1.0 g/d IgAN患者的Th1细胞比例（2.55±1.20）%及Th1/Th2值（1.58±0.43）均较小于1.0 g/d的患者（P〈0.01）;多元线性回归分析显示IgAN患者外周血Th1/Th2比值与血清中IgG/IgA值存在着正相关关系。结论 IgAN患者存在Th2细胞型免疫表达增强,可能与IgA肾病的免疫机制有关;反复发作性肉眼血尿及24 h尿蛋白小于1.0 g/d的IgAN患者外周血的Th细胞亚群呈Th1偏移;IgAN患者的血清中IgG/IgA值对外周血中Th1/Th2比值存在着正相关影响。     

Clinical features and natural history of IgA nephropathy.

IgA nephropathy (IgAN) is the most common form of glomerulonephritis worldwide. It is characterized by recurrent gross hematuria, microhematuria and/or proteinuria and diffuse mesangial IgA deposits in glomeruli. It is predominantly a disease of young males. Apart from primary IgAN (Berger's disease), IgA deposits in the glomeruli are also seen in Henoch-Sch?nlein purpura and in association with various of other diseases, particularly liver cirrhosis. Originally it was thought that IgAN was a benign disease, but it is now known that approximately 20-40% of patients develop progressive renal disease 5 to 25 years after diagnosis and progress to end-stage renal disease. Clinical predictors of progressive disease are elevated serum creatinine concentration at presentation, increased systemic blood pressure, persistent protein excretion > 1.0 g/day and histological predictors are glomerulosclerosis, tubular atrophy/interstitial fibrosis, extension of immune deposits to the perivascular space and crescent formation. Progression correlates more closely with the severity of tubulointerstitial lesions than with the degree of glomerular lesions. These features of IgAN reported in literature were mostly, but not completely, confirmed by analysis of all consecutive patients with biopsy proven IgAN and follow-up > 12 months in the renal units of Heidelberg and Prague using univariate analysis, multiple range test and multiple regression analysis.     

IgA anti-actin antibodies ELISA in coeliac disease: A multicentre study

BACKGROUND: Previous studies have demonstrated that serum anti-actin antibodies are a reliable marker of intestinal damage severity in coeliac disease. AIMS: To validate in a multicentre study the clinical usefulness of serum IgA anti-actin antibody ELISA and its possible use in monitoring intestinal mucosa lesions during gluten-free diet. PATIENTS AND METHODS: Four centres recruited 205 newly diagnosed coeliac disease patients with villous atrophy, 80 healthy controls and 81 "disease" controls. Twelve coeliac disease patients on gluten-free diet but with persistent symptoms underwent serum IgA anti-actin antibody assay and intestinal histology evaluation. IgA anti-actin antibody ELISA was performed with a commercial kit. All coeliac disease patients underwent intestinal histology study. RESULTS: IgA anti-actin antibodies showed a sensitivity of 80% and a specificity of 85% in the diagnosis of coeliac disease patients with villous atrophy. The area under the receiving operator curve for anti-actin antibodies was 0.873 [95% C.I. 0.805-0.899]. Serum anti-actin antibodies values were significantly higher in coeliac disease patients than in healthy or "disease" controls (P<0.0001). Serum anti-actin antibodies were positive in 41 of the 60 coeliac disease patients with mild intestinal histology lesions (69%) and in 123 of the 145 with severe lesions (85.3%) (P<0.05). There was a significant inverse correlation between anti-actin antibody values and the villi/crypts ratio (r=-0.423; P<0.0001). In the 12 coeliac disease patients on gluten-free diet who underwent re-evaluation as they were persistently symptomatic, intestinal histology showed three cases with persistent villous atrophy: all of these were positive for serum anti-actin antibodies ELISA, whereas both serum anti-tTG and EmAs were negative. The other nine patients showed normal intestinal villi and were negative for serum anti-actin antibodies. CONCLUSIONS: Anti-actin antibodies are a reliable marker of severe intestinal mucosa damage in coeliac disease patients and a simple ELISA technique offers an accurate method for their determination. These antibodies seem to be a very reliable marker of persistent intestinal damage in coeliac disease patients.     

IgA肾病患者尿白介素6检测的意义

用白介素6(IL-6)依赖细胞株7TD_1细胞,测定了21例原发性IgA肾病(IgAN)患者尿和血清IL-6活性水平,并分析了IL-6活性水平与IgAN临床及病理改变的联系.结果示IgAN尿及血清IL-6活性均增高(分别占46.7％及25％),尿IL-6活性增高与血清IL-6活性水平无平行关系.尿IL-6活性水平与IgAN严重蛋白尿的发生以及肾小球病变程度(节段肾小球硬化、新月体、系膜增生等)有关,亦与小管-间质病变的严重程度有关.因而尿IL-6测定,对IgAN的临床分析具有十分重要的意义.     

Association of serum IgA and C4 with severe atherosclerosis

To assess the possible involvement of humoral immunity in diffuse atherosclerosis, IgG, IgA, IgM, C3 and C4 were measured in the sera of 23 atherosclerotic subjects (at least 3 stenoses greater than 75% in the arteries of the limbs and neck, as assessed by panangiography) and of 20 controls (possible stenoses less than 40% documented by arteriography of the aortic arch and epi-aortic branches and "normal" response to exercise stress testing and Doppler ultrasonography of the arteries of the lower limbs). Age (59-69) and sex distribution did not differ significantly in the 2 groups. The following serum concentrations were higher in the atherosclerotic subjects than in the controls: C4 (28.7 +/- 6.5 (1 SD) vs. 23.4 +/- 3.8 mg/dl; P = 0.0013); IgA (323.3 +/- 155.0 vs. 210.3 +/- 87.9 mg/dl; P = 0.0020); and C3 (126.3 +/- 16.9 vs. 111.0 +/- 18.9 mg/dl; P = 0.0109). To assess whether these parameters were independently associated with atherosclerosis, a multiple logistic regression was performed, also including other variables which differed between the atherosclerotic group and the control group with P values less than 0.20 (cigarette smoking, arterial hypertension, body mass index, serum HDL-cholesterol, HDL-cholesterol/total cholesterol ratio, serum triglycerides, IgG and IgM). In multivariate analysis only IgA (P = 0.0012), C4 (P = 0.0072), cigarette smoking (P = 0.0141) and serum triglycerides (P = 0.0177) were independently associated with atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Association of gene polymorphism of polymeric immunoglobulin receptor and IgA nephropathy

OBJECTIVE: In order to explore the possibility that genetic predisposition to dysfunction of mucosal immunity and the IgA processing pathway plays a role in the pathogenesis of mesangial IgA1 deposition in IgAN, we examined the possible association of the gene polymorphism of pIgR in the patients with and without IgAN. SUBJECTS AND METHODS: Genomic DNA of peripheral blood cells was isolated from 372 individuals including 172 histologically confirmed IgAN patients. Segments of the pIgR gene were PCR amplified and restriction fragment length polymorphism was determined as A1 and A2 with and without Pvu II site, respectively. RESULTS: The pIgR genotype distribution was significantly different between the patients with IgAN and those without IgAN. Allele frequency of A2 was higher in IgAN than in other renal diseases (A1 and A2; 0.516 and 0.484 in IgAN, 0.641 and 0.359 in others, chi2 = 9.84, P = 0.0017, Odds ratio = 1.71). Moreover, the subjects with A2A2 genotype were associated with a relatively low level of serum IgA only in the patients with IgAN but not in other renal diseases. The difference of allele frequencies was more remarkable in the patients with a serum IgA level of less than 300 mg/dl (A1 and A2; 0.439 and 0.561 in IgAN, 0.702 and 0.298 in others, chi2 = 12.44, P = 0.0004, Odds ratio = 3.01). CONCLUSION: This is the first demonstration of the pIgR gene polymorphisms in IgAN which are associated with its clinical phenotype. Gene polymorphisms of pIgR may be candidate genetic markers of susceptibility to IgAN.     

Renal vascular lesions and the occurrence of hypertension in patients with IgA nephropathy

Worse prognosis of IgA nephropathy (IgAN) is associated to hypertension, high proteinuria, glomerular and vascular sclerosis. A family story of hypertension (FHT) in relatives could be a strong predictor of the occurrence of hypertension (HT) in children. Renal vascular lesions (RVL) are often observed in normotensive patients with IgAN. In order to evaluate a possible association between FHT and LVR in patients with IgAN, we investigated two groups of 73 IgAN patients, sex (56 males and 17 females) and age matched, according to the presence or not of FHT. FHT was diagnosed if relatives and/or at least one child under 60 years of age had treatment for HT or systolic and diastolic BP over 140/90 mmHg at the time of the survey. Patients entering into the study were followed during an average period of 5 to 8 years. At the end of the study, all patients were explored for HT and renal function. Creatinine clearance (CrCl) was evaluated by Cockcroft and Gault formula and renal failure was defined as CrCl<60mL/min. The results were as follow: at the time of renal biopsy, RVL were observed in 73% of males with FHT vs 16% of males without FHT (p<0.0001) and 70.6% of females with FHT vs 29.4% of females without FHT (p<0.001); at the end of the study period, HT was significantly associated to FHT in 89.6% of patients group with FHT vs 22.6% of HT patients in the group without FHT (p<.0001). Renal failure was present in 45.2% of patients with FHT vs 4.1% of patients without FHT (p<0.0001). These data suggest: VRL could be dependent of genetic factors; FHT should be an early predictor of VRL in patients with IgAN; FHT might be a risk factor for renal failure in patients with this renal disease.     

Clinical study of IgA antibody against hepatitis C virus core antigen in patients with type C chronic liver disease

Immunoglobulin A class antibody to hepatitis C virus core antigen (IgA anti-HCc) was measured in the serum of 128 patients with type C chronic liver disease. Fifty-eight patients (45.3%) were seropositive. IgA anti-HCc was detected in only one of 20 patients with chronic persistent hepatitis; however, 52.3% (46/88) of patients with chronic active hepatitis and 55% (11/20) of patients with liver cirrhosis were seropositive. Histological examination revealed that 22 (71.0%) of 31 patients with severe disease activity were seropositive compared to 35 (44.9%) of 78 patients with moderate (P<0.05) and one (5.3%) of 19 patients with mild (P<0.01) histological changes. IgA anti-HCc was measured sequentially in 65 patients who underwent interferon therapy. There was a significant difference between responders and other patients in the mean ratio of IgA anti-HCc titers one month after therapy. Three months after therapy, IgA anti-HCc was detectable in only two of 15 responders who were IgA anti-HCc seropositive at the start of therapy. In contrast, IgA anti-HCc reappeared three months after therapy despite a temporary decrease to undetectable levels in all nonresponders. We conclude that IgA anti-HCc is a useful marker to identify the presence of active type C liver disease and that the disappearance of IgA anti-HCc three months after interferon therapy predicts a good response in treated patients.     

Oxidative Stress and Galactose-Deficient IgA1 as Markers of Progression in IgA Nephropathy

Summary

Background and objectives

We assessed the activation of the oxidative stress pathway in patients with IgA nephropathy (IgAN), while evaluating the classic marker of the disease (galactose-deficient serum IgA1).

Design, setting, participants, & measurements

Sera from 292 patients and 69 healthy controls from Italy and the United States were assayed for advanced oxidation protein products (AOPPs), free sulfhydryl groups on albumin (SH-Alb), and IgA1 with galactose-deficient hinge-region O-glycans (Gd-IgA1). Gd-IgA1 was detected by binding to Helix aspersa agglutinin (HAA) and expressed as total Gd-IgA1 or as degree of galactose deficiency relative to a standard Gd-IgA1 myeloma protein (%HAA).

Results

Sera from IgAN patients showed higher levels of Gd-IgA1, %HAA, and AOPPs, but lower levels of SH-Alb in comparison to that from healthy controls. Serum levels of AOPPs significantly correlated with serum Gd-IgA1 and %HAA. The relationship between these biomarkers and clinical features at sampling and during follow-up was assessed in 62 patients with long-term follow-up. AOPPs and %HAA correlated with proteinuria at sampling and independently associated with subsequent proteinuria. Levels of AOPPs correlated with rate of decline in renal function after sampling. The combination of a high level of AOPPs and a high level of %HAA associated with decline in estimated GFR.

Conclusions

Serum levels of aberrantly glycosylated IgA1 are elevated and oxidative stress pathways are activated in patients with IgAN; the intensity of the stress correlated with expression and progression of the disease. We speculate that oxidative stress may modulate the nephrotoxicity of aberrantly glycosylated IgA1 in IgAN.     

Effect of serum from IgA nephropathy patients on IL-1 production from P388 D1 cell lines]

The study was designed to investigate IL-1 production from P388D1 cell using serum from 40 cases with IgA nephropathy (IgAN) as stimulative factor. It was found that there was a relationship between IL-1 and renal morphological change. The result indicated that IL-1 production by P388D1 cell was much higher in the presence of the serum than that in the absence (CPM: 47597 +/- 26213 vs 36567 +/- 14377 P less than 0.05). The level of IL-1 correlated obviously to the renal morphologic changes (r = 0.406, P less than 0.05). It is suggested that in the serum of IgAN patients there are certain factors stimulating P388D1 cell to produce IL-1, which may contribute to the pathogenesis of IgAN.     

Analysis of the monomeric IgA to polymeric IgA ratio in specific IgA antibodies for Chlamydia trachomatis--clinical studies in chlamydial urogenital infections

Antibody titers of monomeric and polymeric types of serum specific IgA for Chlamydia trachomatis were measured by indirect immunoperoxidase assay (Savyon kit) in male and female cases with various chlamydial urogenital infections. From these results, the ratio of monomeric to polymeric IgA (m/p ratio) was determined. All cases were positive for specific IgA and IgG antibodies for C. trachomatis, and the antigen was also detected in all of cases except for those with prostatitis. 1. Study in males: The m/p ratio (mean +/- S.E.) was 2.6 +/- 1.0 in acute chlamydial urethritis and 8.0 +/- 2.2 in chronic non-bacterial prostatitis. The result indicated monomeric IgA-predominance in the chronic stage. 2. Study in females: The m/p ratio was 5.0 +/- 1.9 in subacute chlamydial cervicitis, while it was 8.5 +/- 2.9 in pregnant women considered to have chronic chlamydial infection. The rate was 31.5 +/- 16.8 in prostitutes considered to have repeated chlamydial infections. The result suggested that monomeric IgA was predominant in patients with chronic and repeated infections. 3. As for sequential changes of IgA antibody titer, polymeric IgA alone decreased after treatment of acute chlamydial urethritis. However monomeric IgA decreased in chronic infection such as prostatitis, and a similar change was shown in IgG antibody. 4. These results suggest that polymeric IgA is predominant in the acute stage of chlamydial infections, while monomeric IgA predominates in the chronic stage.     

Galactose-Deficient IgA1 in African Americans with IgA Nephropathy: Serum Levels and Heritability

Background and objectives: Serum levels of galactose-deficient IgA1 (Gd-IgA1) are elevated and heritable in Caucasian and Asian patients with IgA nephropathy (IgAN), but have not been characterized in African Americans (AA). Our objective was to determine whether serum Gd-IgA1 levels are increased in AA patients with IgAN and whether this is a heritable trait in this group.Design, setting, participants, & measurements: Blood and urine samples were obtained from 18 adult and 11 pediatric AA patients with biopsy-proven IgAN and from 34 of their first-degree relatives. Healthy controls included 150 Caucasian adults, 65 AA adults, 45 Caucasian children, and 49 AA children. Serum total IgA and Gd-IgA1 levels were measured in patients and controls. Significant differences between patient and control groups for serum total IgA, Gd-IgA1, and ratio of Gd-IgA1/total IgA were determined by the Mann-Whitney U test. Heritability was calculated using SOLAR.Results: After stratifying by age, 7 of 11 pediatric and 9 of 18 adult AA patients with IgAN had serum Gd-IgA1 levels above the 95th percentile for age-appropriate AA controls. For first-degree relatives, the serum Gd-IgA1 level was >95th percentile for 1 of 8 when the patient''s level was <95th percentile and 12 of 26 when the patient''s level was >95th percentile (P = 0.116, Fisher exact test). Heritability was 0.74 (P = 0.007).Conclusions: Serum levels of Gd-IgA1 are often elevated in AA patients with IgAN and their first-degree relatives. Thus, aberrant IgA1 glycosylation is a heritable risk factor for IgAN in African Americans.IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide (1). Nonetheless, the condition is rarely diagnosed in sub-Saharan Africans (2,3) and, on the basis of biopsy series, is uncommon in some African-American (AA) cohorts (4–7). Population-based data from central and eastern Kentucky, however, have shown an incidence for IgAN in AA adults similar to that in Caucasians adults (8), raising the possibility that, in some regions of the United States, IgAN may be underdiagnosed in AAs. A lower incidence of IgAN in AA patients could be due to factors such as the lack of early detection because of infrequent testing by urinalysis, delayed referral to nephrology, and decreased likelihood of renal biopsy.The pathogenesis of IgAN is related to aberrant glycosylation of O-linked glycans in the hinge region of IgA1. Rather than terminating with galactose, the aberrant glycans end with N-acetylgalactosamine (GalNAc). This GalNAc moiety, in turn, is recognized by anti-glycan antibodies (9), leading to formation of nephritogenic circulating immune complexes that subsequently deposit in the glomerular mesangium to induce renal injury (10). In vitro studies have shown that these complexes stimulate cultured mesangial cells to proliferate and secrete extracellular-matrix proteins, whereas uncomplexed galactose-deficient IgA1 (Gd-IgA1) or galactose-replete IgA1 does not (11).Serum Gd-IgA1 levels are elevated in Caucasian and Asian patients with IgAN (12–14). Elevated serum Gd-IgA1 levels have also been found to be heritable in a dominant pattern for Caucasian and Chinese patients, although most affected relatives have no clinical manifestation of IgAN (12,15). The purpose of this study was to determine whether the serum levels of Gd-IgA1 in AA patients are increased and are heritable, as is the case for Caucasian and Asian patients with IgAN.     

Heterogeneity of prognosis in adult IgA nephropathy, especially with mild proteinuria or mild histological features

OBJECTIVE: The present study was undertaken to clarify the clinical course and prognosis of adult patients with primary IgA nephropathy (IgAN), especially with mild proteinuria or mild histological alternations. PATIENTS AND METHODS: A population of 735 IgAN patients whom we were able to observe for more than two years was examined. RESULTS: A total of 115 patients (15.6%) was on dialysis during the observation period. The overall 5-year renal survival rate was 92.0%. On the other hand, 166 patients (22.6%) were in clinical remission. A group with mild proteinuria included 197 patients (26.8%). Forty-seven patients of this group showed minor glomerular abnormalities, whereas 12 patients with mild proteinuria showed severe mesangial involvement. Three patients with mild proteinuria were on dialysis during the observation period, whose proteinuria was increased during the clinical course. A group with minor glomerular abnormalities included 82 patients (11.2%). Forty-seven patients of this group showed mild proteinuria, of whom 12 patients showed moderate proteinuria. However, three patients with minor glomerular abnormalities who were not on dialysis showed loss of renal function. CONCLUSION: These results indicated the heterogeneity of the course and prognosis in IgAN. Even if a patient's initial clinical or histological findings are comparatively mild, strict follow-up management is needed.     

Serum levels of KL-6 as a useful marker for evaluating pulmonary fibrosis in patients with systemic sclerosis

OBJECTIVE: KL-6 is a mucin-like glycoprotein that is strongly expressed on type II pneumocytes in the lung. Circulating KL-6 has been shown to be a sensitive marker of the disease activity of interstitial lung diseases. We determined the serum levels of KL-6 in patients with systemic sclerosis (SSc) and investigated whether these levels would serve as a useful marker of pulmonary fibrosis (PF) in patients with SSc. METHODS: The serum KL-6 levels were determined using a specific ELISA in 91 patients with SSc, and in 38 healthy controls. RESULTS: The serum levels of KL-6 were significantly higher in patients with SSc than in healthy controls (923+/-860 vs. 382+/-55 U/ml; p<0.0001). The serum KL-6 levels of the patients with diffuse cutaneous SSc (dSSc) tended to be higher than those with limited cutaneous SSc (ISSc) (1054+/-1000 vs. 800+/-694 U/ml), but there was no significant difference between these 2 groups. The serum KL-6 levels in the patients with PF were significantly elevated compared to those without PF (1283+/-1056 vs. 520+/-148 U/ml; p<0.0001). Moreover, DLCO and VC were also significantly decreased in the patients with elevated KL-6 levels compared to those with normal levels (62+/-22% vs. 72+/-17%, p<0.05; 87 +/-20% vs. 100+/-18%, p<0.01, respectively). CONCLUSION: Serum KL-6 level may be a useful serum marker for evaluating pulmonary fibrosis in patients with SSc.     

甘露糖结合蛋白基因多态性与IgA肾病免疫病理类型的关联

目的根据甘露糖结合蛋白(MBP)基因多态性对其功能的影响,探讨MBP基因多态性与IgA肾病免疫病理间的联系。方法选取1钾例IgA肾病(IgAN)患者,其中77例为肾小球单纯IgA伴沉积,70例为肾小球IgA,IgG,IgM伴C3,C1q沉积。使用PCR-RFLP方法对MBP基因多态性与IgAN免疫沉积的关系进行了观察。结果①本研究中正常人群MBP基因多态性分布与文献报道的华人及高加索人种接近并无显著差异。②IgAN中大量免疫沉积(IgA,IgG,IgM,C3,C1q)患者MBP基因CGC／GAC基因型的发生频率明显高于单纯IgA沉积(IgA,C3)患者(41.4％vs19.5％,P＜0.01),而CGC／GGC基因型的发生频率明显低于单纯IgA沉积患者(55.7％vs76.6％,P＜0.01)。IgAN的大量免疫沉积患者GAC等位基因的发生频率明显高于单纯IgA沉积患者(0.236vs0.136,P＜0.05),而GGC等位基因的发生频率明显低于单纯IgA沉积患者(0.764vs0.864,P＜0.05),GAC等位基因与IgAN的大量免疫沉积明显相关(OR=1.95,95％CI1.06～3.58)     

Profiling of autoantibodies in IgA nephropathy, an integrative antibiomics approach

Summary

Background and objectives

IgG commonly co-exists with IgA in the glomerular mesangium of patients with IgA nephropathy (IgAN) with unclear clinical relevance. Autoantibody (autoAb) biomarkers to detect and track progression of IgAN are an unmet clinical need. The objective of the study was to identify IgA-specific autoAbs specific to IgAN.

Design, setting, participants, & measurements

High-density protein microarrays were evaluated IgG autoAbs in the serum of IgAN patients (n = 22) and controls (n = 10). Clinical parameters, including annual GFR and urine protein measurements, were collected on all patients over 5 years. Bioinformatic data analysis was performed to select targets for further validation by immunohistochemistry (IHC).

Results

One hundred seventeen (1.4%) specific antibodies were increased in IgAN. Among the most significant were the autoAb to the Ig family of proteins. IgAN-specific autoAbs (approximately 50%) were mounted against proteins predominantly expressed in glomeruli and tubules, and selected candidates were verified by IHC. Receiver operating characteristic analysis of our study demonstrated that IgG autoAb levels (matriline 2, ubiquitin-conjugating enzyme E2W, DEAD box protein, and protein kinase D1) might be used in combination with 24-hour proteinuria to improve prediction of the progression of IgAN (area under the curve = 0.86, P = 0.02).

Conclusions

IgAN is associated with elevated IgG autoAbs to multiple proteins in the kidney. This first analysis of the repertoire of autoAbs in IgAN identifies novel, immunogenic protein targets that are highly expressed in the kidney glomerulus and tubules that may bear relevance in the pathogenesis and progression of IgAN.     

Effect of Tonsillectomy Plus Steroid Pulse Therapy on Clinical Remission of IgA Nephropathy: A Controlled Study

Background and objectives: Few well-designed investigations have examined how tonsillectomy plus steroid pulse therapy affects IgA nephropathy. A prospective, controlled study therefore was performed to compare the effects of combined therapy with those of steroid pulse alone in patients with IgA nephropathy.Design, setting, participants, & measurements: Fifty-five patients were followed up for 54.0 ± 21.2 mo. Thirty-five of them underwent tonsillectomy and steroid pulse therapy (group C), and 20 received steroid pulse monotherapy (group M). Both groups received methylprednisolone intravenously, followed by oral prednisolone (initial dosage 0.5 mg/kg per d) for 12 to 18 mo. Primary evaluation items were a 100% increase in serum creatinine from baseline levels or the disappearance of urinary protein (UP) and/or occult blood (UOB) indicating clinical remission.Results: At 24 mo after the initial treatment, the ratios of the UP and UOB disappearance were higher in group C than in group M, and the therapeutic effect persisted until the final observation. None of group C achieved a 100% increase in serum creatinine from the baseline level, whereas one patient in group M developed ESRD during the observation period. The histologic findings of repeated biopsy specimens from 18 patients revealed that mesangial proliferation and IgA deposition were significantly more reduced in group C than in group M. The Cox regression model showed that the combined therapy was approximately six-fold more effective in causing the disappearance of UP than steroid pulse monotherapy.Conclusion: Tonsillectomy combined with steroid pulse treatment can induce clinical remission in patients with IgA nephropathy.The most widespread type of glomerulonephritis is IgA nephropathy (IgAN), and the renal outcome is relatively poor: 30 to 40% of patients reach ESRD within 20 yr (1,2). Various treatment strategies have been attempted to improve the renal outcome of IgAN (3), and corticosteroids, immunosuppressive agents, and angiotensin-converting enzyme inhibitors seem to show promise (4–8); however, IgAN treatment remains controversial because study populations and lead-time bias differ considerably among studies (9,10).Hotta et al. (11) initially described tonsillectomy combined with steroid pulse therapy, which then became a popular approach to treating IgAN for several years in Japan. A retrospective analysis showed that approximately 60% of their patients who underwent tonsillectomy combined with steroid administration achieved remission of urinary abnormalities. The results of their recent multicenter, prospective, cohort study (12) indicated that the remission rate of urinary abnormalities depends on clinical severity defined as the level of serum creatinine (sCr) and proteinuria; however, precise information about the effectiveness of the combination therapy against IgAN remains scarce.Here, we conducted a prospective, nonrandomized, controlled study to assess whether the tonsillectomy combined with steroid pulse therapy is more effective than steroid pulse monotherapy in patients with IgAN. We determined the therapeutic effects on the basis of remission of urinary abnormalities and histologic findings.     

Soluble ICAM-1 in patients with chronic hepatitis C infection: a prognostic marker of disease activity

Soluble intercellular adhesion molecule-I (sICAM-1) is an important early marker of response to inflammatory mediators and immune activation released from a variety of cells including hepatocytes. At present, the most reliable determination of severity and prognosis in chronic viral hepatitis is the histological staging of the disease which is an invasive procedure and is often not well accepted by patients. The search for alternative non-invasive methods is mandatory especially in follow ups after initial assessment by biopsy. Serum sICAM-1 level was measured in 19 patients with chronic HCV, 19 patients with non-B, non-C chronic liver diseases (NBNC-CLD) and in 19 healthy control subjects using ELISA. Serum sICAM-1 levels were significantly higher in patients with chronic HCV and in NBNC-CLD patients compared to normal subjects (mean +/- SD, [1003 +/- 453 vs. 232 +/- 177, p<0.001], and [881 +/- 328 vs. 232 +/- 177, p<0.001]), respectively. Furthermore, serum levels of sICAM-1 were significantly higher in HCV-RNA positive patients than in HCV-RNA negative patients (p<0.001). Positive correlations were detected between serum levels of sICAM-1 and serum alanine aminotranseferase (ALT) (p<0.001), aspartate aminotranseferase (AST) (p<0.001), prothrompin time (p<0.001), and alkaline phosphatase (p<0.001), while, a negative correlation with albumin was found (p<0.001). Also, there was a significant correlation between clinical, ultrasonic findings and the level of sICAM-1 in chronic HCV patients as regards hepatomegaly, splenomegaly and normal liver echogenecity. High knodell score was significantly associated with high sICAM-1 level (p<0.001) in both patient groups. while no association between sICAM-1 and fibrosis was found. In conclusion, the measurement of sICAM-1 serum levels in chronic hepatitis C and NBNC-CLD patients is a useful non-invasive marker for monitoring liver disease activity that could replace follow up liver biopsies that are mostly not welcomed by the patients.