Epstein-Barr virus genome-positive tubulointerstitial nephritis associated with immune complex-mediated glomerulonephritis in chronic active EB virus infection

 Renal involvement is rare in chronic active Epstein-Barr (EB) virus infection. We report a case of a 7-year-old girl with recurrent EB virus infection. She had fever, lymphadenopathy, hepatosplenomegaly, and persistently high titres of IgG to EB virus capsid antigen (VCA) and IgG to EB early antigen with low titres of IgM to VCA. She showed mild haematuria and proteinuria, but had no symptoms of renal failure. Renal biopsy revealed immune complex-mediated glomerulonephritis, which may have been due to a persistently high titre of antibody against EB virus. In addition, a peculiar form of tubulointerstitial nephritis was found. The morphology was characterized by a papillary infolding of the tubular epithelial cell layer into the tubular lumen. The interstitium was surrounded by the infolded epithelium and contained a large number of B-cell dominant lymphocytes. EBV-encoded RNA 1 (EBER-1) gene was detected in the nuclei of some tubuloepithelial cells by in situ hybridization and may have been associated with the pathogenesis of tubulointerstitial nephritis. Received: 28 October 1997 / Accepted: 19 Decembeer 1997     

Fibrillary glomerulonephritis mimicking membranous nephropathy – A diagnostic pitfall

Kidney biopsies in 2 females with nephrotic syndrome were suggestive of membranous nephropathy at routine light microscopy and immunohistochemistry. Electron microscopy on re-embedded paraffin tissue, however, revealed that the light microscopic pattern was due to a fibrillary glomerulonephritis with a dominant membranous manifestation.     

An electron microscopic study of glomerular lesions in hereditary nephrotic mice (ICGN strain)

Summary Glomerular lesions in hereditary nephrotic mice (ICGN strain) were investigated by electron microscopy. The glomeruli of unaffected animals, which appeared normal by light microscopy, had developed an ultrastructural change in the glomerular capillary basement membrane (GCBM). There was a partial thickening of the GCBM with bilaminar splitting of the lamina densa and an electron-dense fibrillar material exhibiting cross-striations. In affected animals, light microscopy revealed a marked thickening of GCBM and an increase of mesangial matrix without cellular proliferaton. By electron microscopy, multilaminar splitting of the lamina densa in the thickened GCBMs and fusion of the epithelial foot processes were observed. In some severely affected animals, immune complex deposition was found in GCBM, but little if any was observed in other animals. In the end, the glomeruli were globally sclerosed. Our findings suggest that initial structural abnormalities in GCBM may play an important role in the onset and development of the disease, though subsequent events such as immune complex deposition would modify the disease.     

Involvement of dipeptidyl peptidase IV in immune complex-mediated glomerulonephritis

Dipeptidyl peptidase IV (DPPIV) is widely expressed in many tissues; however, its precise biological function is poorly understood. One of its possible physiologic roles is an involvement in the immune system, which plays a pivotal role in the pathogenesis of glomerulonephritis. The present study focused on the involvement of DPPIV in immune complex-mediated glomerulonephritis. Experimental nephritis was induced by anti-Thy-1.1 monoclonal antibody E30 using Wistar or F344 rats. The application of a new monoclonal antibody against DPPIV, F16, completely suppressed E30-induced proteinuria and mesangial proliferation in Wistar rats, whereas these preventive effects of F16 were not observed in F344 rats, which spontaneously lack DPPIV protein. Treatment with F16 inhibited glomerular deposition of complement C3 and complement C4 after the binding of E30 to the mesangial cell surface. Because the preventive effect of F16 was attributable to suppression of the complement cascade, we examined its influences on complement-dependent mesangial cell lysis in vitro. We discovered that the complement cascade was markedly inactivated in F16-treated Wistar rat serum but not in F16-treated F344 rats. These results indicate that DPPIV may play a somewhat crucial role in regulating the complement cascade and that inhibition of DPPIV may serve as a new target for preventing complement-dependent tissue injury.     

Circulatory antigen of Heymann nephritis. III. Presence of the 70-kD circulatory protein in the immune deposits of Heymann nephritis.

An antigen of 70 kD size has been isolated previously from normal rat serum which has immunological cross-reactivity to the Heymann nephritis antigen, F x 1A. Its role in the pathogenesis of Heymann's nephritis was unknown. In this investigation we tested for the presence of 70-kD circulatory antigen in the glomerular immune deposits of Heymann's nephritis. Further, its presence was correlated with severity of disease. It was observed that the presence of the 70-kD antigen strongly correlated with the existence of electron-dense deposits in the lamina rara externa (LRE) of the glomerular capillary wall and with pathologic proteinuria. Temporally, the presence of the 70-kD antigen in the immune deposits was followed by large electron-dense deposits, enhanced complement activity and proteinuria. The data suggest that in the growing immune complex lattice in the LRE, the 70-kD circulatory antigen by virtue of its small size, mobility and antigen cross-reactivity facilitates cross linking and coalescence of immune complexes, resulting in electron-dense immune deposits (EDD) formation which initiates complement activation and consequent proteinuria.     

Amelioration of immune complex-mediated glomerulonephritis by synthetic protease inhibitors.

Proteases are involved in the pathogenesis of inflammatory diseases by participating in the activation of mediator systems and by producing proteolytic tissue injury. Homeostatic control of inflammation is accomplished in part by physiologic protease inhibitors. The authors investigated the effectiveness of a number of synthetic protease inhibitors in ameliorating the glomerular injury induced by immune complex-mediated glomerulonephritis in mice. Two amidine-type protease inhibitors, bis (5-amidino-2-benzimidazolyl)methane and 1,2-bis (5-amidino-2-benzimidazolyl)ethane, had the greatest effects. They caused a marked reduction in glomerular necrosis (P less than 0.001) but did not affect the amount or site of immune complex localization or leukocyte influx. The inhibition constants of the protease inhibitors against nine purified physiologic proteases were determined. These results were discussed in relation to the effectiveness of the protease inhibitors in reducing glomerular injury. This investigation indicates that the administration of synthetic protease inhibitors can have a beneficial effect on immune-mediated inflammatory injury.     

Localization of glomerular 'deposits' in Henoch-Schönlein nephritis

Twenty-five renal biopsies from patients with Henoch-Schönlein nephritis were examined using light microscopy, immunofluorescence, I μm plastic-embedded sections and electron microscopy. The I μm plastic-embedded sections and electron microscopy showed deposits in mesangial, subendothelial and subepithelial sites. Some of the latter were very large and similar to those which have been described as 'humps' in acute proliferative glomerulonephritis. Immunofluorescence showed the mesangial deposition of IgG, IgA and C₃ with extension into a peripheral position in some cases. Fibrin was frequently found associated with crescents. The case for Henoch-Schönlein disease being mediated, in part at least, by immune complex deposition, is presented.     

Glomerular localization of preformed immune complexes in nephrotoxic serum nephritis

Summary Pre-formed immune complexes solubilized in antigen excess were infused into rats with nephrotoxic serum nephritis and normal control animals. Complex localization was evident in seven of ten nephrotoxic animals suggesting that the presence of immune mediated glomerular injury makes the kidney susceptibility to further immune injury.Supported by Grant MA-6122, Medical Research Council of Canada     

B cells in glomerulonephritis: focus on lupus nephritis

The production of pathogenic antibody has been traditionally viewed as the principle contribution of B cells to the pathogenesis of immune-mediated glomerulonephritis. However, it is increasingly appreciated that B cells play a much broader role in such diseases, functioning as antigen-presenting cells, regulators of T cells, dendritic cells, and macrophages and orchestrators of local lymphatic expansion. In this review, we provide an overview of basic B cell biology and consider the evidence implicating B cells in one of the archetypal immune-mediated glomerulonephritides, lupus nephritis.     

Light and electron microscopic findings in five cases of cryoglobulinemic glomerulonephritis

Summary Renal tissue from five patients with cryoglobulinemia was studied by light and electron microscopy and immunofluorescence. None of the histologic features observed at the light microscopic level seems to be specific for cryoglobulinemia. Electron microscopic investigations have shown very large electron dense deposits in almost every examined lobule in all cases. The deposits displayed two main patterns; a homogeneous texture in two cases and tubular or annular structures in three cases. The patients with typically structured deposits had IgG-IgM cryoglobulinemia (2 cases) or monoclonal IgM cryoglobulinemia (1 case). The presence of IgM in cryoglobulinemia may be the cause of the peculiar structure of the deposits.     

Hereditary sclerosing poikiloderma

Hereditary sclerosing poikiloderma (HSP) is a very rare disease. The clinical features are principally widespread poikiloderma and linear hyperkeratotic and sclerotic bands. We report an 18-yr-old male who presented reticular hyperpigmented lesions on the trunk and extremities since 2-yr-old. Also, linear sclerosing bands appeared on both antecubital and popliteal fossae after yr. Histopathologic finding showed dense sclerotic collagen fibers with telangiectasia in the upper dermis and fragmentations of damaged elastic fibers in the elastic stain, consistent with HSP. We report the first Korean case of HSP.     

Hereditary diffuse leukoencephalopathy with spheroids: ultrastructural and immunoelectron microscopic studies

Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a rare autosomal dominant disorder characterized by cerebral white matter degeneration with myelin loss and axonal swellings (spheroids) leading to progressive cognitive and motor dysfunction. Histopathology of HDLS has been well characterized, but ultrastructural details are lacking. Here we report ultrastructural and immunoelectron microscopic characterization of spheroids and capillary basal lamina in white matter of HDLS brains. Spheroids had thin or discontinuous or no myelin sheaths. They contained various combinations of aggregated neurofilaments (NF), cytoplasmic organelles, dense bodies, and laminated figures. Aggregated filaments labeled with antibodies to phosphorylated NF (pNF), non-pNF and amyloid precursor protein. The gliotic white matter had many reactive astrocytes, and lipid-laden macrophages with membranous and fingerprint-like bodies. The basal laminas (BL) of many capillaries were dilated, and the enlarged space was heavily deposited with banded collagen type I and III. Some BL had focal thickenings and duplications. Fibronectin, not collagen IV, was found associated with banded collagen. The various types of axonal spheroids and changes in capillary basal lamina have not been emphasized previously. It remains to be determined if they are a reactive process or a primary mechanism of white matter degeneration in HDLS.     

A case of comma-shaped fibrillary glomerulonephritis

We present a case of a 77-year-old male with multiple co-morbidities who underwent a renal biopsy for progressive loss of renal function. Examination by electron microscopy revealed glomerular deposits within which were numerous randomly orientated 22 nanometre mean diameter curvilinear fibrils, consistent with a rare form of fibrillary glomerulonephritis. Review of the literature has revealed just one similar case. The investigative work up and histological findings are discussed along with the clinical implications of making a diagnosis of fibrillary glomerulonephritis.     

Hydroxychloroquine-induced Phospholipidosis in a Case of SLE: The Wolf in Zebra Clothing

Abstract

A 30 year old lady patient of SLE on steroid and hydroxychloroquine therapy presented with lupus nephritis and later developed cardiac symptoms. Her renal biopsy revealed features of Class III lupus nephritis. Also seen was typical lamellated myelinoid material in the glomerulus. The alpha-galactosidase A activity was normal. The clinical morphological and biochemical findings were consistent with Lupus nephritis showing changes of hydroxychloroquine induced phopholipidosis. Electron microscopy along with careful clinical examination and follow up status was instrumental in the diagnosis of the latter.     

创伤相关性黄色肉芽肿性间质肾炎的临床与病理分析

目的：探讨黄色肉芽肿性间质肾炎（XGIN）的发病机制、病变本质、组织学特点及其对临床的指导意义。方法：综合分析有关病史与CT、彩超、静脉尿路造影及其余实验资料；并同术中发现与病理检验对比分析。结果：全组病人均于本病发作4－12年前遭受腰背或腰肋部钝挫伤。各个病人的手术前中后临床诊断皆为“肾癌”而施行根治性手术。“瘤灶”中心位于皮质区并向肾外周“侵袭”。病变局部以大量的泡沫样细胞堆积及间质成片纤维化伴较多的淋巴细胞浸润为主要镜下特征，经免疫组化证实为黄色肉芽肿性而非肿瘤性。肾盂肾盏无明显的炎细胞浸润；无尿路感染、梗阻或结石的证据。结论：XGIN可能是创作免疫介导的一 种迟发性肉芽肿；明确其发病机制与病变特点是临床正确诊断与治疗的前题。     

Hereditary angioedema and aortitis

Summary A 28-year-old male with hereditary angioedema died of an extensive stroke. Autopsy revealed cicatricial aortitis with narrowing of the coronary ostia, myocardial infarctions, and a left ventricular mural thrombus. There was neither acute inflammation of the aorta nor systemic vasculitis. A possible association of the aortitis with the hereditary angioedema is discussed.Abbreviations ANA Antinuclear antibodies - C1-INA C1-inactivator - CH 50 Total hemolytic complement - HBS-AG Hepatitis surface antigen - TPHA Treponema pallidum hemagglutination - VDRL Agglutination reaction for syphilis     

A study by immunofluorescence microscopy of the NC1 domain of collagen type IV in glomerular basement membranes of two patients with hereditary nephritis

Summary The NC1 domain of the collagen type IV molecule, the major component of glomerular basement membranes (GBM), consists of dimers and 24 kilodalton (K), 26 K and 28 K monomers in man, and contains the Goodpasture antigen. Serum obtained from patients with Goodpasture's syndrome has been reported not to stain GBM of most male and some female patients with hereditary nephritis (HN) by immunofluorescence (IF) microscopy. In the present study, GBM seen on the renal biopsies of 2 patients (one male and one female) with HN were examined by IF to ascertain whether NC1 monomers were detectable. Three reagents were used: a plasmapheresis fluid (PPF) obtained from a patient who was treated for anti-GBM nephritis (human anti-GBM PPF); a commercial rabbit antibody against human NC1; and a rabbit antibody raised by us against dog NC1, which cross-reacted with human NC1. All 3 reagents detected NC1 determinants in GBM of normal human kidney by IF and reacted with human NC1 by a plate-binding radioimmunoassay (RIA). The human anti-GBM PPF bound to 28 K and 26 K monomer components of NC1 by Western blotting, the rabbit anti-human NC1 antibody bound to 26 K and 24 K monomers, while the rabbit anti-dog NC1 antibody bound only to the 26 K monomer. By IF, the human anti-GBM PPF did not stain GBM of the male patient with HN, but produced segmental staining of GBM (i.e., some GBM stained, while others did not) of the female patient. In contrast, the rabbit anti-NC1 antibodies produced global staining by IF of GBM of both patients. The absence of staining (i.e., global or segmental) seen with the human anti-GBM PPF implied that the 26 K and 28 K monomers of NC1 were either absent from GBM, or were present but altered structurally, leading to a diminution in their immunological reactivity. However, the positive staining observed with the rabbit anti-NC1 antibodies implied that the 26 K monomer was actually present in GBM. Hence, we postulate that the 26 K monomer of NC1 in GBM was structurally altered, and that the 28 K monomer was either absent, or present but altered. These findings suggest that there is an abnormality of more than one monomer of NC1 in GBM of patients with HN.