Induction of IgA against Haemophilus parainfluenzae antigens in tonsillar mononuclear cells from patients with IgA nephropathy

Much evidence suggests that IgA production in vivo and in vitro is enhanced in patients with IgA nephropathy (IgAN). We have demonstrated glomerular deposition of the outer membranes of Haemophilus parainfluenzae (HP) antigens (OMHP) and the presence of HP-specific IgA in the serum of patients with IgAN. In this study, we investigated the production of IgA and several cytokines by tonsillar mononuclear cells (TMC) from IgAN patients induced by stimulation with OMHP. The spontaneous production of total IgA and TGF-beta by TMC from IgAN patients was higher than that by TMC from patients with chronic tonsillitis (CT) (P < 0.05). Stimulation with OMHP in vitro enhanced the production of HP-specific IgA by TMC from IgAN patients (P < 0.01), but not by TMC from CT patients. OMHP stimulation also enhanced the production of TGF-beta and IL-10 by TMC from IgAN patients (P < 0.001). These results suggest that the infection of HP in the tonsil may be involved in the etiology of IgAN.     

Increase in tonsillar germinal centre B-1 cell numbers in IgA nephropathy (IgAN) patients and reduced susceptibility to Fas-mediated apoptosis

IgAN is a common form of primary glomerulonephritis and also a disease of tonsillar focal infection. The comprehensive mechanism underlying this disease remains to be defined. To better understand its pathogenesis, we investigated tonsillar CD5+ B cells (B-1 cells) with respect to IgA synthesis. Germinal centre (GC) B cells were isolated from the tonsils of IgAN patients and the number of B-1 cells in the GC determined by flow cytometry. GC B-1 and B-2 (CD5- B) cells were purified by cell sorter, the cells were incubated with agonist anti-CD40 MoAb and the ability for antibody production by B-1 and B-2 cells determined by ELISPOT assay. GC B-1 cells and B-2 cells were incubated with agonist anti-Fas MoAb, and apoptosis in GC B-1 cells and B-2 cells was analysed by flow cytometry. Although B-1 cells do not usually take part in the GC reaction, an increase in B-1 cell numbers was observed in the GC of tonsils from IgAN patients. These B-1 cells were likely IgA1 antibody-producing cells, since the prominent IgA subclass in IgAN is generally considered to be IgA1. Although Fas-dependent apoptosis is essential for the elimination of activated B cells, these B-1 cells showed a reduced susceptibility to Fas-mediated apoptosis. It is conceivable that activated B-1 cells may survive in the GC due to impaired apoptosis and thus produce abnormal antibodies. These findings suggest that the immune responses of B-1 cells in the tonsillar GC could thus have an impact on the pathogenesis of IgAN.     

Systemic immune response after mucosal immunization in patients with IgA nephropathy

Increased IgA production has been proposed as a portion of the etiology of IgA nephropathy. Indirect human data suggest that IgG and complement may be equally important. We have immunized 17 patients with IgA nephropathy and 27 controls with tetanus toxoid. They were nasally immunized and, 2 weeks later, received an im booster immunization. This protocol has been shown to result in an increased serum IgA1 antibody response to tetanus toxin (TT). Patients had higher serum IgG antibodies to TT before and after the im immunization than did controls (pre, 42 vs 13 U; post, 155 vs 71 U;P=0.004). Patients also had a greater increase in serum IgG antibodies (118 vs 58;P=0.02). After the im TT, patients had lower levels of serum IgA1 antibody to TT (115 vs 180;P=0.005) but the change in IgA1 antibodies was not significant. These data suggest that patients with IgA nephropathy may produce inappropriately large amounts of serum IgG antibodies to antigens encountered in the upper respiratory tree. Such antigens also induce a serum IgA1 response. Such a response could result in the formation of potentially nephritogenic immune complexes containing IgG, IgA1, and C3.     

Binding capacity and pathophysiological effects of IgA1 from patients with IgA nephropathy on human glomerular mesangial cells

IgA deposition in glomerular mesangium and the interaction with mesangial cells may well be the final common pathway to IgA nephropathy (IgAN). Altered hinge-region O-glycosylation of IgA1 from patients with IgAN may predispose to mesangial deposition and activation of the mesangial cell (MC) by IgA1, via a novel IgA1 receptor, and may be a key event in the pathogensis of IgAN. The aim of this study was to investigate the binding capacity and biological effects of IgA1, from both patients with IgAN and healthy controls, on human mesangial cells (HMC). Serum IgA1 was isolated with jacalin affinity chromatography, heated to aggregated form (aIgA1) and labelled with (125)I. Binding capacity of aIgA1 in vitro to cultured primary HMC was evaluated by a radioligand binding assay and the specificity of binding was determined by a competitive inhibition assay. Intracellular calcium release was studied by confocal analysis and phosphorylation of extracellular signal-regulated kinase (ERK) was determined by Western blot analysis. Change of cell cycles was demonstrated by flow cytometry and HMC proliferation was evaluated by direct cell count. Expression of TGF-beta mRNA and production of supernatant fibronectin were tested by RT-PCR and indirect competitive ELISA, respectively. aIgA1 from both the patients with IgAN and normal controls bound to HMC in a dose-dependent, saturable manner, and was saturated at approximately 500 pmoles per 0.5 ml of aIgA1. aIgA1 from patients with IgAN, however, bound to HMC at a higher speed and Scatchard analysis revealed a Kd of (8.89 +/- 2.1) x 10(-8)m versus (4.3 +/- 1.2) x 10(-7)m for aIgA1 from healthy controls (P = 0.026).The binding was specific because it was only inhibited by unlabelled Mono-IgA1 (mIgA1) and not by serum albumin or IgG. aIgA1 from patients with IgAN could induce release of intracellular calcium, phosphorylation of ERK, DNA synthesis, proliferation of HMC, expression of TGF-betamRNA and secretion of fibronectin in HMC in a similar time-dependent manner as aIgA1 from healthy controls, but the effects were much stronger and the durations were much longer (P < 0.05, respectively). We conclude that aIgA1 from patients with IgAN has a higher binding capacity to HMC and stronger biological effects than aIgA1 from healthy controls. This suggests that direct interaction between IgA1 and HMC and subsequential pathophysiological responses may play an important role in the pathogenesis for IgAN.     

Oligoclonally expanding gammadelta T lymphocytes induce IgA switching in IgA nephropathy

The aetiology of IgA nephropathy (IgAN) is closely related with abnormality of mucosal immunity. We investigated the roles of γδ T cells in the regulation of IgA production by B cells in IgAN patients. The proportion of γδ T cells in peripheral blood mononuclear cells (PBMNC) was higher in IgAN patients than in the controls and was found to be correlated with the proportion of surface IgA‐positive (sIgA+) B cells, which are precursors of IgA‐secreting plasma cells. After in vitro PWM stimulation, sIgA expression on B cells and IgA production were significantly enhanced in PBMNC obtained from IgAN patients, whereas the enhancements were abolished by removal of γδ T cells from the PBMNC. Purified γδ T cells from IgAN patients induced surface IgA expression on naïve sIgD+ B cells more effectively than did αβ T cells. Moreover, stimulated γδ T cells from IgAN patients produced a larger amount of TGF‐β1, which is one of the main cytokines that induces IgA class switching on B cells, as compared with αβ T cells and control γδ T cells. The expanded γδ T cells from IgAN patients exclusively expressed Vγ9, and the nucleotide sequences of junctional regions of Vγ9 showed very limited TCR diversities. It was therefore concluded that γδ T cells, which are expanded in response to specific antigens, enhance IgA class switching on B cells in IgAN patients.     

Analysis of microbial changes in the tonsillar formalin-fixed paraffin-embedded tissue of Chinese patients with IgA nephropathy

BackgroundImmunoglobulin A nephropathy (IgAN) is a prevalent chronic glomerular disease contribution to end-stage renal failure (ESRD). The tonsillar microbiota is closely associated with IgAN diseases based on the mucosal immune response. However, the composition and function of in tonsillar microbiota in participant patients with IgAN remains unknown. In this study, we detected the tonsillar microbiota changes of IgAN patients in Heilongjiang province located in northeast China.Material and methodsWe collected from 21 patients with IgAN and 16 patients with chronic tonsillitis (CT) who had undergone tonsillectomy previously. Histological review of all samples from formalin-fixed paraffin-embedded (FFPE) tissue were performed. Extracted DNA from FFPE tissue blocks, after that V4 regions of 16S ribosomal RNA (rRNA) sequencing and comparative analyses of tonsillar flora between two groups were performed. The statistical analysis used the SPSS version of 21.ResultsVisualization of microorganisms by Gram and Warthin-Starry (WS) silver stains, preliminarily observed the morphological characteristics of microbiome in FFPE tissue cases, such as bacteria or fungi. Tonsillar FFPE samples from the IgAN patients and CT controls showed significant differences in tonsillar microbial certain compositions and functions. We found that there were eight dominant genera that can be available to distinguish IgAN patients from CT controls. Compared with CT controls, at genus level, the relative abundances of Methylocaldum and unclassified_f_Prevotellaceae were significantly higher, while the abundances of Anaerosphaera, Halomonas, Trichococcus, Peptostreptococcus, norank_f_Synergistaceae and unclassified_k_norank_d_Bacteria were significantly lower in IgAN patients. Principal co-ordinates analysis (PCOA) distinguished IgAN patients from CT controls, and receiver operating characteristic (ROC) curves analysis confirmed that the diagnosis of disease has certain diagnostic significance. In addition, Functional analysis revealed that partly Enzymes and KOs were increased in the IgAN patients.ConclusionsHistological screening results were very helpful for further gene sequencing, not only to supplement the observation of bacterial morphology and structure, but also to prepare for subsequent gene sequencing and bioinformatics analysis. We elucidated subtle relevance between changes in tonsillar microbiota and IgAN patients, which can be utilized to predict the incidence of IgAN disease. In addition, we predicted that some enzymes, and KOs were closely related to IgAN.     

Induction of IgA against Haemophilus parainfluenzae Antigens in Tonsillar Mononuclear Cells from Patients with IgA Nephropathy

Much evidence suggests that IgA production in vivo and in vitro is enhanced in patients with IgA nephropathy (IgAN). We have demonstrated glomerular deposition of the outer membranes of Haemophilus parainfluenzae (HP) antigens (OMHP) and the presence of HP-specific IgA in the serum of patients with IgAN. In this study, we investigated the production of IgA and several cytokines by tonsillar mononuclear cells (TMC) from IgAN patients induced by stimulation with OMHP. The spontaneous production of total IgA and TGF-β by TMC from IgAN patients was higher than that by TMC from patients with chronic tonsillitis (CT) (P < 0.05). Stimulation with OMHP in vitro enhanced the production of HP-specific IgA by TMC from IgAN patients (P < 0.01), but not by TMC from CT patients. OMHP stimulation also enhanced the production of TGF-β and IL-10 by TMC from IgAN patients (P < 0.001). These results suggest that the infection of HP in the tonsil may be involved in the etiology of IgAN.     

Immunopathological features of palatine tonsil characteristic of IgA nephropathy: IgA1 localization in follicular dendritic cells

IgA nephropathy (IgAN) is generally thought to be mediated by the glomerular deposition of circulating immune complexes containing IgA as the major antibody component. Upper respiratory infections and tonsillitis often precede IgAN. and in some cases tonsillectomy is affective for the (treatment of IgAN. Thus, the tonsil seems to be a unique organ causing initial and/or progressive events to generate nephritogenic immune complexes in IgAN. in this study we focused on the analysis of immunopathological features of the palatine tonsil characteristic of IgAN patients by using an immunohistochemical technique. The IgAl subclass was demonstrated in follicular dendritic cells (FDC) of the tonsil of IgAN patients, but not in FDC of non-IgAN controls. On the other hand, IgA2, IgG, IgM and C3 did not show any differences in distribution between the two groups. Moreover, the expression of decay-accelerating factor (DAF), an inhibitor of homologous complement activation, and transforming growth factor-beta I (TGF-/β1). an inducer of antibody-producing ceils to IgA class switching, in FDC and interdigitating dendritic cells of the tonsil, respectively, which was also clarified in this study for the first time, was found to be identically distributed in the two groups. These findings may support the idea that IgA1. possibly in an immune complex form, is trapped by FDC and plays an important role in the persistent activation of particular B cell repertoires responsible for ihe onset and/or progression of IgAN.     

Capsaicin induces high expression of BAFF and aberrantly glycosylated IgA1 of tonsillar mononuclear cells in IgA nephropathy patients

Background

IgA nephropathy (IgAN) is the most common type of primary glomerulonephritis in the world. Hot pepper is the most favorite vegetable for Chinese in Hunan and Sichuan provinces. It can be assumed that capsaicin, the active ingredient of hot pepper, is a possible risk factor in diet in the pathogenesis of IgAN.

Methods

22 subjects, including 11 IgAN patients and 11 non-IgAN patients were enrolled in this study. Tonsillar mononuclear cells were isolated and cultured for 3 days with or without capsaicin.

Results

In the absence and presence of capsaicin, the BAFF expression and IgA1 secretion were higher in IgAN patients than that in non-IgAN patients, meanwhile, the gene expression of C1GALT1 and Cosmc and IgA1 O-glycosylation level were significantly lower. In IgAN group, coincubated with capsaicin, IgA1 and BAFF secretion and BAFF expression by TMCs were significantly higher than that without capsaicin, furthermore, the level of mRNA encoding C1GALT1 and Cosmc and the level of IgA1 O-glycosylation were evidently lower.

Conclusion

Capsaicin may induce IgA1 secretion by activating BAFF expression, and bring to aberrantly IgA1 O-glycosylation by suppressing C1GALT1 and Cosmc expression. Therefore, to limit the consumption of hot pepper would be beneficial to patients with IgA nephropathy.     

Secretory immunoglobulin A (IgA) responses in IgA nephropathy patients after mucosal immunization, as part of a polymeric IgA response

Secretory immunoglobulin A (SIgA), although generated at mucosal surfaces, is also found in low concentrations in the circulation. Recently, SIgA was demonstrated in mesangial deposits of patients with immunoglobulin A nephropathy (IgAN), suggesting a role in the pathogenesis. This finding is in line with the belief that high molecular weight (HMW) immunoglobulin A (IgA) is deposited in the kidney. However, there is little information on the size distribution of antigen-specific IgA in circulation upon mucosal challenge. In this study we measured antigen-specific IgA, including SIgA, in serum following challenge of IgAN patients and controls via intranasal vaccination with a neoantigen, cholera toxin subunit B (CTB). We size-fractionated serum and nasal washes to study the size distribution of total IgA, SIgA and CTB-specific IgA. Finally, we compared the size distribution of antigen-specific IgA after mucosal immunization with the distribution upon systemic immunization. A significant induction of antigen-specific SIgA was detectable in serum of both patients with IgAN and controls after mucosal immunization with CTB. Independent of the route of immunization, in both groups the antigen-specific IgA response was predominantly in the polymeric IgA fractions. This is in contrast to total IgA levels in serum that are predominantly monomeric. We conclude that mucosal challenge results in antigen-specific SIgA in the circulation, and that the antigen-specific IgA response in both IgAN patients and in controls is of predominantly HMW in nature. No differences between IgAN patients and controls were detected, suggesting that the size distribution of antigen-specific IgA in the circulation is not disturbed specifically in IgAN patients.     

Possible involvement of mast cells in renal fibrosis in patients with IgA nephropathy

Objective: The objective of the present study is to investigate whether human mast cells (MC) contribute to renal damage through local activation of the renin-angiotensin system, by assessing their numbers in renal biopsy specimens from patients with IgA nephropathy (IgAN) or minimal change nephrotic syndrome (MCNS). Methods: In patients with IgAN and MCNS, the numbers of tryptase-positive MC (MC(T)) and MC positive for both tryptase and chymase (MC(TC)) were examined histopathologically. Serum creatinine level, mean blood pressure and the severity of glomerular and tubulointerstitial lesions were also determined. Results: MC(TC) numbers differed between IgAN patients and MCNS patients. IgAN patients had more MC(TC) than MC(T). MC were found around but not in the conglomerate of the AngiotensinII (AngII)-positive cells. In the IgAN patients with the most severe pathology, the number of AngII-positive cells was correlated with that of MC(TC) and MC(T). Conclusion: Chymase-dependent AngII synthesis due to human MC may be involved in the inflammatory and fibrotic processes of IgAN. Received 4 September 2006; returned for revision 27 October 2006; returned for final revision 21 December 2006; accepted by M. Katori 30 May 2007     

炎症介质在IgA肾病中的临床应用价值探讨

目的探讨hs-CRP、IL-6、IL-18、TNF-α和TGF-β1在Ig A肾病中的临床应用价值。方法选取2010年6月至2013年11月肾穿刺活检确诊的Ig A肾病患者71例,根据病理Lee氏分级的结果将Ig A肾病组分为3个亚组,轻度组(Ⅰ级+Ⅱ级)32例,中度组(Ⅲ级)17例,重度组(Ⅳ级+Ⅴ级)22例;同时选取35例健康对照。检测各组血清Scr、Urea、CysC和尿UTP水平及血清炎症因子hs-CRP、IL-6、IL-18、TNF-α和TGF-β1水平,并比较各炎症因子与Scr、Urea、CysC和尿UTP的相关性。结果 Ig A肾病患者各组血清hs-CRP、IL-6、IL-18、TNF-α和TGF-β1水平逐渐增高,与健康对照组有显著性差异(P<0.05);随着疾病进展,重度组各炎症因子水平与轻度组和中度组比较有显著性差异(P<0.05);各炎症因子与Scr、Urea、CysC和尿UTP呈正相关(P<0.05)。结论炎症介质可以监测肾损伤程度,炎症损伤与Ig A肾病进展有密切关系。     

Galactosylation of N- and O-linked carbohydrate moieties of IgA1 and IgG in IgA nephropathy

The mechanism of IgA deposition in the kidneys in IgA nephropathy is unknown, Mesangial IgA is of the IgA I subclass, and since no consistent antigenic target for the IgA I has been described, we have investigated the glycosylation of the molecule, as a potential non-immunological abnormality which may contribute to its deposition. IgA 1 is rich in carbohydrate, carrying N-linked moieties in common with IgG, but also O-linked sugars, which are rare in serum proteins, and not expressed by IgG or lgA2, Lectin binding assays were designed to examine the expression of terminal galactose on the N-linked carbohydrate chains of purified serum IgG and IgAI, and the O-linked sugars of IgAI and C1 inhibitor (one of the very few other serum proteins with O-linked glycosylation). No evidence was found for abnormalities of N-linked glycosylation of either isotype in IgA nephropathy compared with matched controls. However, in IgA nephropathy, reduced terminal galactosylation of the hinge region O-linked moieties was demonstrated; this was not seen in C1 inhibitor, which showed normal or increased galactosylation of the O-linked sugars. This abnormality of IgA1 has considerable implications for the pathogenesis of IgA nephropathy, since the O-linked sugars lie in an important functional location within the IgA1 molecule, close to the ligand of Fc receptors. Changes in the carbohydrates in this site may therefore affect interactions with receptors and extracellular proteins, leading to anomalous handling of the IgA1 protein in this condition, including failure of normal clearance mechanisms, and mesangial deposition.     

Immune response to Haemophilus parainfluenzae in patients with chronic obstructive lung disease

Haemophilus parainfluenzae is often isolated from the sputa of patients with chronic obstructive lung disease. We have investigated the immune response to this organism in patients with chronic bronchitis (n = 3) and bronchiectasis (n = 10) and in healthy controls (n = 9). Outer membrane proteins (OMPs) of H. parainfluenzae were purified for use in enzyme-linked immunosorbent and immunoblot assays. Whole-cell H. parainfluenzae preparations were used to adsorb antibodies from serum samples, which were subsequently immunoblot assayed to investigate the antibody response to surface-exposed epitopes. Levels of H. parainfluenzae-specific immunoglobulin G (IgG), but not IgA or IgM, were increased in the sera of patients with chronic obstructive lung disease compared to levels in control subjects. The species specificity of the antibody response was confirmed, although a degree of cross-reactivity with H. influenzae antigens was observed. IgA and IgG specific for OMPs of H. parainfluenzae were demonstrated to be present in the sputa and sera of five patients with chronic obstructive lung disease. Variation in the pattern and intensity of antigen recognition was observed among patients and among immunoglobulin classes. OMPs of approximately 36, 22, and 15 kDa were confirmed to possess epitopes exposed on the surface of intact H. parainfluenzae. We have demonstrated the presence of a species-specific systemic immune response to H. parainfluenzae in colonized patients. A specific antibody response was also observed in sputum, and the antigen specificity of these responses in patients with chronic obstructive lung disease was investigated for the first time. The presence of a specific immune response suggests that H. parainfluenzae may have a pathogenic role in patients with chronic obstructive lung disease.     

Urinary IgA in IgA nephropathy and Henoch-Schoenlein purpura

To determine the concentrations and molecular forms of urinary IgA in IgA nephropathy and Henoch-Schoenlein purpura, we studied 29 patients with these IgA-associated renal diseases (IgAN). Control groups comprised 10 patients with other diverse renal diseases and 11 healthy volunteers. Urinary IgA and IgG concentrations were higher in IgAN than in either control group and correlated positively with the serum creatinine concentration as well as the urinary protein excretion (P<0.01). However, IgA/IgG ratios did not differ among the three groups. Polymeric IgA (p-IgA) in the urine predominated only in normals; in IgAN and patients with other renal diseases, monomeric IgA (m-IgA) occurred almost exclusively. Serum IgA concentrations were generally normal in IgAN; four patients had concentrations greater than 500 mg/dl. Although the fraction of p-IgA in serum (median, 18%) was increased above normal (5–10%) in 13 of 16 (81%) subjects, neither the concentration of IgA or IgG nor the amount of p-IgA correlated with the serum creatinine concentration. These data suggest that the molecular form and concentration of urinary IgA are not discriminating for IgAN and are independent of these characteristics of serum IgA.     

IgA nephropathy with subendothelial deposits

Summary IgA nephropathy with subendothelial deposits in the capillary walls of the glomeruli (IgA type 2) was compared histometrically and clinically with IgA nephropathy without subendothelial deposits (IgA type 1) and membranoproliferative glomerulonephritis with subendothelial deposits (MPGN). Study cases consisted of 32 biopsies from 26 patients of IgA type 1, 25 biopsies from 20 patients of IgA type 2 and 31 biopsies from 27 patients of MPGN. Histological changes of the glomeruli consisted of an increase in the mesangial matrix and hypercellularity in the mesangium in both types of IgA nephropathy, and the degree of the changes was a little higher in IgA type 2 than in IgA type 1 (0.02<P<0.05). Mesangial changes of MPGN were marked as compared with IgA type 1 and IgA type 2 (P< 0.001). Histometry of the mesangium on the cases followed up showed that the degree of mesangial thickening increased with lapse of time in IgA type 2 and MPGN, whereas it remained unchanged up to 13 years in IgA type 1. Proteinuria tended to be mild in IgA type 1, moderate in IgA type 2, and marked in MPGN. The impairment of renal function was observed in 21.9% of IgA type 1, in 36.0% of IgA type 2 and in 58.1% of MPGN. IgA type 2 has been shown to be pathologically and clinically intermediate between IgA type 1 and MPGN. These results suggest that there is a clinicopathological overlap between IgA nephropathy and MPGN with IgA deposition.     

Abnormalities of the IgA immune system in members of unrelated pedigrees from patients with IgA nephropathy.

In the last few years many investigators have reported the recurrence of primary IgA nephropathy (IgAN) or the presence of persistent microhaematuria and/or proteinuria in family members of patients with IgAN. Our study was undertaken to investigate the relevance of abnormalities in the regulation of the IgA and IgM immune system in microhaematuric and asymptomatic family members of IgAN patients. Fifty-four out of 120 members of nine unrelated pedigrees were examined by urinalysis; polymeric IgA (pIgA), IgA rheumatoid factor (IgARF), IgA1-IgG immune complexes (IgA 1-IgG IC) and IgA 1-IgM IC, and other immunoglobulins were measured in serum samples. Moreover, we studied the production of immunoglobulins, pIgA and IgARF by peripheral blood mononuclear cells (PBMC) in basal conditions and after pokeweed mitogen (PWM) stimulation. Our data demonstrate that persistent microhaematuria was present in 24% of relatives. High serum levels of IgA, mainly pIgA and IgARF, IgA 1-IgG IC and IgA 1-IgM IC occurred in 66% of relatives. Abnormal spontaneous production of IgA by PBMC and after PWM stimulation was present in 64% of family members. Interestingly, high serum levels of IgM and abnormal production of this immunoglobulin by PBMC were observed in relatives. However, the immunological abnormalities did not correlate in any way with the presence of urinary abnormalities such as microhaematuria, which was most likely determined by an underlying glomerular alteration.     

Aberrant sialylation of serum IgA1 was associated with prognosis of patients with IgA nephropathy

Aberrant glycosylation of serum IgA1 was considered as an initial event and involvement in the pathogenesis of IgAN. We previously demonstrated that aberrant glycosylation of serum IgA1 was associated with pathologic phenotype of IgAN. The present study is to investigate if abnormal sialylation of IgA1 affects renal survival of IgAN. 127 patients with biopsy-proven IgAN were enrolled and followed up to 8 years. Seventy-nine healthy and 75 patients with non-IgAN renal diseases were selected as controls. Alpha 2, 6 sialic acid (SA) of serum IgA1 was measured by sandwich-ELISA. Renal survival rate was estimated by Kaplan-Meier method. Alpha 2, 6 SA level in patients with IgAN was lower than that in healthy controls (0.92+/-0.14 vs. 0.98+/-0.12, P=0.001) and non-IgAN glomerulonephritis (0.92+/-0.14 vs. 1.00+/-0.18, n=53, P=0.001). Patients with IgAN in Low SA Group were no significant differences compared with patients in Normal SA Group in age, gender, hypertension, serum creatinine, and excretion of proteinuria. Renal cumulative survival rate was 53.3% in patients in Low SA Group and 83.5% in Normal SA Group (P=0.0008). The lower the alpha 2, 6 SA level of serum IgA1 in patients with IgAN was, the worse their renal survival rate was. Although patients in Low SA Group had worse renal function evaluated by eGFR, there was no significant difference in various CKD stages in non-IgAN renal function controls (n=42, P=0.352). Alpha 2, 6 SA level of serum IgA1 was associated with the prognosis of patients with IgAN and could serve as a predictor of poor prognosis in IgAN.     

Expression profile of Fc receptor-like molecules in patients with IgA nephropathy

BackgroundFc receptor-like (FCRL) molecules were considered to play a role in the pathogenesis of certain autoimmune diseases. Nonetheless, the clinical significance of FCRLs in IgA nephropathy (IgAN) remains unclear.ObjectiveThis study is aimed at investigating the expression levels of FCRLs molecules in IgAN patients and determining its relevance to disease activity.MethodsThe mRNA expression levels of FCRLs were determined in peripheral blood mononuclear cells (PBMCs) of 42 IgAN patients and 48 healthy controls by quantitative real-time PCR (qRT-PCR). FCRLs proteins expression in B cells of 25 IgAN patients, 14 patients with non-IgAN glomerulonephritis, and 29 healthy controls were detected by Flow cytometry. The Spearman correlation test was used to assess the correlation of FCRLs expression with clinical parameters of IgAN patients.ResultsOur results indicated significant down-regulation of FCRL2 and FCRL3 mRNA levels in IgAN patients compared to healthy subjects. Surface protein expression of FCRLs molecules confirmed the qRT-PCR results. But FCRL2 and FCRL3 protein levels did not correlate with clinicopathologic phenotypes of IgAN patients. However, we found a significant positively correlation of FCRL2 and FCRL3 mRNA expression with the core 1 β1,3-galactosyltransferase (C1GALT1) and its molecular chaperone (Cosmc) mRNA levels in IgAN patients.ConclusionsFCRL2 and FCRL3 expression levels in IgAN patients are significantly decreased and correlated with CIGALT1 and Cosmc mRNA expression.