Immunopathology of ocular sarcoidosis

Summary Sarcoidosis is a multisystem disease characterized by enhanced immune responses at sites of involvement. To elucidate the immunopathogenesis of ophthalmic lesions, cell infiltrates in biopsies from conjunctiva and other tissues involved (lungs, lymph nodes, skin) were studied in 26 patients with active sarcoidosis in order to define the surface phenotype and the distribution of cells in granulomatous lesions. Biopsy specimens were also stained for detection of immunoglobulins, complement and fibrinogen deposits. The data demonstrate a lymphocytes/macrophages interaction in the central core of granulomatous areas as the crucial event that initiates the maintains the state of inflammation: at all sites of disease activity is present a compartmentalization of T-cells expressing a helper-related phenotype which account for the great majority of infiltrating cells both in the early lesions (aggregate of macrophages surrounded by lymphocytic infiltrate) and in well-organized sarcoid granulomata. The presence of plasma cells and immunoglobulin deposits may represent an epiphenomenon in line with the helper infiltration, suggesting a local hyper-reactivity of the B-cells immune system. This study suggests some immunopathogenetic mechanisms leading to the formation and growth of conjunctival sarcoid granulomata.     

Epstein-Barr virus latent and replicative gene expression in oral hairy leukoplakia

Oral hairy leukoplakia is an epithelial lesion of the tongue associated with productive infection by Epstein-Barr virus (EBV). However, no data concerning the pattern of EBV latent gene expression have been reported, and it remains unresolved whether true latent infection occurs in basal cell layers of oral hairy leukoplakia. We have studied six cases of oral hairy leukoplakia using monoclonal antibody immunohistology for EBV latent--EB nuclear antigen (EBNA) 1, EBNA 2 and latent membrane protein 1 (LMP 1); immediate-early (BZLF1); and replicative (EA, VCA, MA) proteins, and for the EBV-receptor (CD21 antigen). EBV DNA was demonstrated by nucleic acid in situ hybridization. Mid- to upper-zone keratinocytes contained EBV DNA and co-expressed EBNA 1, EBNA 2 (5 of 6 cases), LMP 1, BZLF1 protein, EA, VCA and MA. No EBV genome or gene expression could be demonstrated in basal or parabasal cells. Spinous keratinocytes were labelled by anti-CD21 antibodies HB5 and B2, but did not express the EBV-receptor as defined by reactivity with OKB7. The co-expression of latent and replicative infection-associated antigens is striking, indicating possible functional roles for latent proteins during the productive cycle. Our results suggest that oral hairy leukoplakia is caused by repeated direct infection of upper epithelial cells with virus from saliva or adjacent replicatively infected cells, rather than by a latent EBV infection of basal epithelial cells with a differentiation-dependent switch to productive infection as previously proposed.     

Similarities and differences of human and experimental mouse lymphangiomas.

Lymphangioma is a disfiguring malformation of early childhood. A mouse lymphangioma model has been established by injecting Freund's incomplete adjuvant (FIA) intraperitoneally, but has not been compared with the human disease. We show that, in accordance with studies from the 1960s, the mouse model represents an oil-granuloma, made up of CD45-positive leukocytes and invaded by blood and lymph vessels. Several markers of lymphatic endothelial cells are expressed in both mouse and human, like CD31, Prox1, podoplanin, and Lyve-1. However, the human disease affects all parts of the lymphovascular tree. We observed convolutes of lymphatic capillaries, irregularly formed collectors with signs of disintegration, and large lymph cysts. We observed VEGFR-2 and -3 expression in both blood vessels and lymphatics of the patients, whereas in mouse VEGFR-2 was confined to activated blood vessels. The experimental mouse FIA model represents a vascularized oil-granuloma rather than a lymphangioma and reflects the complexity of human lymphangioma only partially.     

Immunohistochemistry of Small Round Blue Cell Tumors of Childhood

Abstract

Small round blue cell tumors in childhood represent a diagnostic category of tumors that show no distinguishing morphologic features but require accurate identification because of their requirement for specific therapies and different clinical outcomes. While the use of ancillary investigations such as cell culture, cytogenetics, and molecular analysis has contributed to their identification and our understanding of their pathogenesis, electron microscopy and immunohistology have proven to be the most practical diagnostic tool in this category of tumors. In the majority of cases, a carefully selected panel of antibodies allows the identification of rhabdomyosarcoma, leukemia/lymphoma, neuroblastoma, Ewing's sarcoma/peripheral neuroepithelial tumors, desmoplastic small round cell tumor, and mesenchymal chondrosarcoma. Although no single antibody is specific, the combination of a number of positive and negative markers produces an immunohistochemical profile that is relatively specific to each of these tumors. To aid understanding of the immunophenotype and histogenesis, molecular aspects of each lesion is briefly discussed. (The J Histotechnol 22:239, 1999)     

Heterogeneity of stromal cells in the human splenic white pulp. Fibroblastic reticulum cells,follicular dendritic cells and a third superficial stromal cell type

At least three phenotypically and morphologically distinguishable types of branched stromal cells are revealed in the human splenic white pulp by subtractive immunohistological double-staining. CD271 is expressed in fibroblastic reticulum cells of T-cell zones and in follicular dendritic cells of follicles. In addition, there is a third CD271⁻ and CD271^+/− stromal cell population surrounding T-cell zones and follicles. At the surface of follicles the third population consists of individually variable partially overlapping shells of stromal cells exhibiting CD90 (Thy-1), MAdCAM-1, CD105 (endoglin), CD141 (thrombomodulin) and smooth muscle α-actin (SMA) with expression of CD90 characterizing the broadest shell and SMA the smallest. In addition, CXCL12, CXCL13 and CCL21 are also present in third-population stromal cells and/or along fibres. Not only CD27⁺ and switched B lymphocytes, but also scattered IgD⁺⁺ B lymphocytes and variable numbers of CD4⁺ T lymphocytes often occur close to the third stromal cell population or one of its subpopulations at the surface of the follicles. In contrast to human lymph nodes, neither podoplanin nor RANKL (CD254) were detected in adult human splenic white pulp stromal cells. The superficial stromal cells of the human splenic white pulp belong to a widespread cell type, which is also found at the surface of red pulp arterioles surrounded by a mixed T-cell/B-cell population. Superficial white pulp stromal cells differ from fibroblastic reticulum cells and follicular dendritic cells not only in humans, but apparently also in mice and perhaps in rats. However, the phenotype of white pulp stromal cells is species-specific and more heterogeneous than described so far.     

Value of laboratory investigations in clinical suspicion of cytomegalovirus-induced upper gastrointestinal tract ulcerations in HIV-infected patients

To assess the value of laboratory investigations for the diagnosis and treatment of cytomegalovirus-induced upper gastrointestinal tract ulcerations, the medical records and biopsy material from HIV-infected patients were reviewed retrospectively during a 12-month period. Clinical diagnosis of cytomegalovirus (CMV) ulceration, based on characteristic endoscopic appearance of extensive ulceration of the mid- to distal esophageal or gastric mucosa and responsiveness to anti-CMV therapy, was compared with laboratory investigations of biopsies. Laboratory procedures consisted of both histopathological examination of the biopsy specimens and viral culture. Twenty episodes in 12 HIV-infected patients could be evaluated. Clinical diagnosis of CMV ulceration appeared to be justified in 14 of 20 episodes (70%), which were confirmed by laboratory investigations. Of the remaining six episodes, which showed partial or no response to anti-CMV therapy, laboratory investigations were negative in two episodes and discrepant in four episodes (histopathology or viral culture positive). A good response to anti-CMV therapy was more frequent in patients whose biopsies proved positive by histopathological examination and/or viral culture than in patients with negative tests (82% versus 0%), which indicates the importance of both investigations. In conclusion, laboratory diagnosis of CMV-induced upper gastrointestinal tract ulcerations supported the diagnosis and decisions on treatment of CMV-induced upper gastrointestinal tract ulcerations. © 1996 Wiley-Liss, Inc.     

Immunomodulatory treatment strategies in inflammatory cardiomyopathy: current status and future perspectives

Chronic autoimmunity and viral persistence constitute prognostic factors for adverse outcome in dilated cardiomyopathy patients. Inflammatory cardiomyopathy is a specific cardiomyopathy entity diagnosed in approximately 50% of dilated cardiopmyopathy patients by immunohistological quantification of immunocompetent infiltrates and cell adhesion molecule abundance. Patients with autoimmune inflammatory cardiomyopathy benefit from immunosuppressive treatment and immunoadsorption by improvement of left ventricular ejection fraction and heart failure symptoms, paralleled by a significant suppression of intramyocardial inflammation. However, dilated cardiomyopathy patients with viral persistence do not respond favorably to immunosuppression.     

Sonic hedgehog信号通路Smo蛋白及其下游转录因子Glil蛋白在胃癌组织中的表达及其意义

目的探讨Sonic hedgehog信号通路Smo蛋白及其下游转录因子Gli1蛋白在胃癌组织中的表达及其意义。方法收集85例胃癌组织及25例正常胃粘膜组织构建成组织芯片，应用免疫组化S—P法检测胃癌组织中Smo蛋白及Gli1蛋白的表达，并以正常胃粘膜组织作对照，分析两者的相关性。结果Smo和Gli1蛋白均在正常胃粘膜中不表达或弱表达；在胃乳头状腺癌、管状腺癌、低分化腺癌中，两者的表达强度和阳性表达率显著高于正常胃粘膜（P〈0．05，并随着胃腺癌分化程度下降而上升；相关分析显示Smo和Gli1蛋白在胃癌组织中的表达呈正相关，相关系数为0．989，P〈0．001。结论胃癌发生过程中的Sonic hedgehog信号通路异常激活可能通过Smo蛋白高表达上调下游转录因子Gli1蛋白的表达参与部分胃腺癌的发生。