Post-MRSA infection glomerulonephritis with marked Staphylococcus aureus cell envelope antigen deposition in glomeruli

A 48-year-old male developed massive proteinuria and renal dysfunction after pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) infection. Examination of a renal biopsy specimen by light microscopy showed severe mesangiocapillary proliferative glomerulonephritis with fibrocellular crescents. Immunofluorescence microscopy showed weak linear staining for immunoglobulin G (IgG), while both the peripheral and mesangial lesions stained for IgA and C3. Immunostaining for a possible antigen related to post-MRSA infection glomerulonephritis, using monoclonal antibody S1D6, revealed marked deposition of S.aureus cell envelope antigen in the glomeruli. Electron-dense deposits were observed in both the subendothelial and the mesangial areas. Focal subendothelial widening accompanied with monocytes or foam cell infiltration was also seen. The findings reflect a typical post-MRSA infection glomerulonephritis caused by S.aureus cell envelope antigen.     

Favorable outcome of crescentic IgA nephropathy associated with methicillin-resistant Staphylococcus aureus infection

Dominant or codominant IgA deposits in the setting of proliferative glomerulonephritis usually indicate IgA nephropathy, Henoch-Sch?nlein purpura nephritis, or, sometimes, lupus nephritis. However, a new type of poststaphylococcal glomerulonephritis with predominantly IgA deposition has been increasingly reported. Herein, we report an unusual case of rapidly progressive glomerulonephritis following methicillin-resistant Staphylococcus aureus infection. Renal biopsy showed crescentic IgA nephropathy. The renal function improved after eradication of infection and administration of immunosuppressive therapy. Although the limited data support the use of immunosuppressive agents in this setting, one must proceed with caution. We suggest that immunosuppressive therapy should only be an option if the underlying infection has definitely been well controlled while the renal disease still progresses.     

多配体蛋白聚糖4是糖尿病肾病的候选基因

目的 在2型糖尿病肾病(DN)白蛋白尿易感基因定位的基础上,进一步筛选白蛋白尿易感基因位点(UA-1)区域附近的候选基因.方法 提取20周龄雄性KK/Ta(n=3)和BALB/c (n=2)小鼠肾脏总RNA,应用Affymetrix Murine Genome U74Av2基因芯片检测肾脏基因表达谱.选择UA-1区域的差异表达基因多配体蛋白聚糖4(syndecan-4),竞争性RT-PCR验证基因芯片的结果.提取KK/Ta、BALB/c小鼠的基因组DNA,进行syndecan-4基因编码区和启动子区域的序列分析.结果 在2型糖尿病KK/Ta小鼠UA-1区域附近存在着约10个差异表达基因.其中syndecan-4在20周龄KK/Ta小鼠肾脏中的表达上调,为BALB/c小鼠的26.1倍.在syndecan-4基因编码区存在2个基因多态性,分别为A93C和T216C多态性,2者均为同义突变.在syndecan-4基因启动子区域存在3个基因多态性,分别为-T263C、-T396C 与-G669A多态性.TATA框位于转录起始位点上游321 bp处,-T263C处恰好为转录因子Clox 的结合位点.结论 syndecan-4基因位于2型糖尿病UA-1附近区域,在20周龄KK/Ta小鼠肾脏中的表达明显上调,是DN的候选基因.syndecan-4启动子处的基因多态性可能为其差异表达的原因.     

The genetic susceptibility to IgA nephropathy: a novel functional candidate gene for incomplete O-glycosylation of IgA1

Incompleteness of O-glycosylation in the IgA1 hinge has been implicated as a central mechanism in the development of IgA nephropathy. Although underglycosylation was reported to be an acquired abnormality, genes for enzymes of O-glycosylation, such as C1GALT1, may be responsible for susceptibility to IgA nephropathy.     

新型IgA肾病病理分型解读

IgA肾病是目前世界范围内最常见的肾小球肾炎.北京大学第一医院肾内科近15年来肾活检病理资料分析显示IgA肾病占所有原发性肾小球疾病的58.2%[1].     

Detection of enriched Thomsen-Friedenrich antigen on IgA1 from IgA nephropathy patients

BACKGROUND: Human serum IgA1 has a mucin-like structure on its hinge portion which is composed of a mucin-type sugar chain and amino acid sequence rich in proline, serine and threonine. There are incompletely glycosylated O-linked oligosaccharide(s) on the IgA1 hinge region in some nephropathy patients. METHODS: We made a detailed analysis of the incompleteness of the sugar chain by digesting IgA1 with various glycosidases. To verify the incompleteness of the sugar chains, the galactosamine/glucosamine ratio (O/N ratio) was introduced as a specific value for each IgA1 preparation. RESULTS: When IgA1 from serum was treated with alpha-N-acetylgalactosaminidase and/or neuraminidase or endo-beta-N-acetylglucosaminidase H (Endo-H), the O/N ratio did not change. However, endo-alpha-N-acetylgalactosaminidase (Endo-A) reduced the O/N ratio of IgA1 from the IgA nephropathy patient whereas before treatment, the O/N ratio had been similar in the normal control and IgA nephropathy. CONCLUSIONS: This result means there is a small amount of the unsubstituted and the sialylated N-acetylgalactosamine residues (Tn and sialyl Tn antigen, respectively), and abundant asialo Galbeta1,3GalNAc (TF antigen) in the IgA1 molecule. In view of the incompleteness of the IgA1 sugar chain, the decrease in the sialic acid content of the mucin-type sugar chain on IgA1 from an IgA nephropathy patient became obvious in this experiment.     

An increased polymeric IgA level is not a prognostic marker for progressive IgA nephropathy.

BACKGROUND: Elution of IgA from renal biopsies of patients with primary IgA nephropathy (IgAN) has suggested that mesangial IgA deposits are mainly multimeric in nature. This macromolecular IgA consists of dimeric and polymeric IgA and may be derived from the circulation. In children with IgAN, circulating macromolecular IgA levels correlate with bouts of macroscopic haematuria, but in adults a correlation with disease activity is less clear. Therefore, we have designed a novel method to assess the levels of polymeric IgA (pIgA) in sera from patients and controls. METHODS: A novel precipitation assay using recombinant CD89 was developed to measure pIgA. Polymeric IgA levels were measured in serum samples obtained from healthy volunteers (n = 21) and patients with IgAN (n = 51). Subsequently, serum pIgA levels were correlated with clinical parameters of disease. RESULTS: Serum pIgA levels were significantly increased in patients with IgAN. However, pIgA concentrations relative to total IgA were significantly lower in sera of patients with IgAN. No correlation was found between serum pIgA levels and clinical parameters of IgAN, such as decline of glomerular filtration rate, haematuria or proteinuria. CONCLUSIONS: Although absolute levels of serum pIgA are increased in patients with IgAN as compared with controls, levels of pIgA relative to total serum IgA are lower. No significant correlation was found between serum concentrations of pIgA and clinical parameters of disease. These data support the notion that it is not the size alone, but the physicochemical composition of the macromolecular IgA that is the key factor leading to mesangial deposition.     

IgA nephropathy is not a rare disease in the United Kingdom

A retrospective analysis of all renal biopsies performed in the Grampian Region of Scotland during 1977-1980 revealed that IgA nephropathy was the most frequently encountered glomerular lesion. The commonest indications for renal biopsy were the presence of asymptomatic urinary abnormalities (90/184; 48.9%) especially asymptomatic haematuria (42/184; 22.8%). A histological diagnosis was made in 36 of the 42 patients presenting with asymptomatic haematuria (85.7%); 16 of the 26 cases of IgA nephropathy presented in this way. Overall, IgA nephropathy was detected in 14.1% of all biopsies and accounted for 21.8% of primary glomerular diseases. This study indicates that IgA nephropathy is apparently more common in Grampian than elsewhere in the United Kingdom. However, it is suggested that this does not represent a true variation in the prevalence of the condition; IgA nephropathy is probably a common cause of haematuria in the United Kingdom.     

IgA肾病临床诊治的一些新认识

IgA肾病是最常见的肾小球疾病,目前仍然是导致我国终末期肾病的最重要原因。起病后10年约20%的患者进展至终末期肾病。但是由于IgA肾病病因不清,发病机制与多种因素有关,临床、病理表现的多样化及预后的异质性,迄今为止,对于IgA肾病尚无特效的治疗方法。临床治疗主要是缓解症状和延缓病情进展,包括一般治疗如饮食限制、血压控制、RAS阻断剂的应用等。IgA肾病中是否应该使用糖皮质激素、免疫抑制治疗和扁桃体切除等,临床上还缺少支持临床决策的高质量证据,关于这个问题的国际共识也是缺乏的。本文就当前有关IgA肾病的治疗新进展做一述评。     

IgA nephritis in HIV-positive patients: a new HIV-associated nephropathy?

Four HIV-positive patients were shown to have IgA-associated nephritis on biopsy, including one with anaphylactoid purpura. Three were homosexuals, while the fourth acquired the infection from his mother. All had hematuria, a variable degree of proteinuria and renal disease with a benign course. Serologic studies showed elevated levels of IgA as well as IgA immune complexes and rheumatoid factor. IgA antibodies to multiple HIV antigens were detected by Western blot. Pathologic studies showed tubuloreticular inclusions in endothelial cells and nuclear bodies in interstitial cells in all cases. HIV antigens were not detected in kidney biopsies by monoclonal antibodies nor was HIV viral genome demonstrated by in situ hybridization. The possibility that this represents a unique type of IgA-associated HIV nephropathy is discussed.     

Evidence for IgA-specific B cell hyperactivity in patients with IgA nephropathy

Spontaneous in vitro IgA synthesis by peripheral blood mononuclear cells (PBMC) of patients with IgA nephropathy was elevated; 419 +/- 71 ng/10(6) cells (Mean +/- SEM) compared with controls; 217 +/- 35 (P less than 0.02). Pokeweed mitogen (PWM) stimulated IgA synthesis was also elevated in patients; 4326 +/- 1140 ng/10(6) cells (Mean +/- SEM) versus 1458 +/- 406 (P less than 0.02) but the PWM stimulation index for patients did not differ significantly from that of the controls. Concanavalin A (Con A) suppression of PWM stimulated IgA synthesis resulted in the generation of similar quantities of IgA by PBMC from both patients and controls but the percentage suppression was significantly elevated in patients; 87 +/- 5 (Mean +/- SEM) versus 58 +/- 10 (P less than 0.05). Synthesis of IgG and IgM followed the same pattern as that described for IgA. T and B cells from patients and controls were cultured alone and in various co-culture permutations. Enriched B cells of patients demonstrated a selectively increased capacity for IgA production; 266 +/- 106 ng/5 X 10(5) cells (Mean +/- SEM) compared with controls; 42 +/- 9 (P less than 0.01) and this parameter correlated significantly with serum IgA concentrations (R = 0.77, P less than 0.05). Overall analysis of co-culture data showed no significant difference between the influences of autologous, control or patient T cells on immunoglobulin synthesis by normal B cells. Autolymphocytotoxic antibodies were not detected and, compared with controls, patient sera had no differential effect on numbers of IgA producing cells generated in culture.(ABSTRACT TRUNCATED AT 250 WORDS)