Clinical & Developmental Immunology最新文献

{"title":"Immunology and oxidative stress in multiple sclerosis: clinical and basic approach.","authors":"Genaro G Ortiz, Fermín P Pacheco-Moisés, Oscar K Bitzer-Quintero, Ana C Ramírez-Anguiano, Luis J Flores-Alvarado, Viridiana Ramírez-Ramírez, Miguel A Macias-Islas, Erandis D Torres-Sánchez","doi":"10.1155/2013/708659","DOIUrl":"10.1155/2013/708659","url":null,"abstract":"<p><p>Multiple sclerosis (MS) exhibits many of the hallmarks of an inflammatory autoimmune disorder including breakdown of the blood-brain barrier (BBB), the recruitment of lymphocytes, microglia, and macrophages to lesion sites, the presence of multiple lesions, generally being more pronounced in the brain stem and spinal cord, the predominantly perivascular location of lesions, the temporal maturation of lesions from inflammation through demyelination, to gliosis and partial remyelination, and the presence of immunoglobulin in the central nervous system and cerebrospinal fluid. Lymphocytes activated in the periphery infiltrate the central nervous system to trigger a local immune response that ultimately damages myelin and axons. Pro-inflammatory cytokines amplify the inflammatory cascade by compromising the BBB, recruiting immune cells from the periphery, and activating resident microglia. inflammation-associated oxidative burst in activated microglia and macrophages plays an important role in the demyelination and free radical-mediated tissue injury in the pathogenesis of MS. The inflammatory environment in demyelinating lesions leads to the generation of oxygen- and nitrogen-free radicals as well as proinflammatory cytokines which contribute to the development and progression of the disease. Inflammation can lead to oxidative stress and vice versa. Thus, oxidative stress and inflammation are involved in a self-perpetuating cycle. </p>","PeriodicalId":55254,"journal":{"name":"Clinical & Developmental Immunology","volume":" ","pages":"708659"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3794553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40277215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LMW heparin prevents increased kidney expression of proinflammatory mediators in (NZBxNZW)F1 mice.","authors":"Annica Hedberg,&nbsp;Premasany Kanapathippillai,&nbsp;Ole Petter Rekvig,&nbsp;Kristin Andreassen Fenton","doi":"10.1155/2013/791262","DOIUrl":"https://doi.org/10.1155/2013/791262","url":null,"abstract":"<p><p>We have previously demonstrated that continuous infusion of low molecular weight (LMW) heparin delays autoantibody production and development of lupus nephritis in (NZBxNZW)F1 (B/W) mice. In this study we investigated the effect of LMW heparin on renal cytokine and chemokine expression and on nucleosome-mediated activation of nucleosome-specific splenocytes. Total mRNA extracted from kidneys of heparin-treated or -untreated B/W mice was analysed by qPCR for the expression of several cytokines, chemokines, and Toll-like receptors. Splenocytes taken from B/W mice were stimulated with nucleosomes with or without the presence of heparin. Splenocyte cell proliferation as thymidine incorporation and the expression of costimulatory molecules and cell activation markers were measured. Heparin treatment of B/W mice reduced the in vivo expression of CCR2, IL1 β , and TLR7 compared to untreated B/W mice. Nucleosome-induced cell proliferation of splenocytes was not influenced by heparin. The expression of CD80, CD86, CD69, CD25, CTLA-4, and TLR 2, 7, 8, and 9 was upregulated upon stimulation by nucleosomes, irrespective of whether heparin was added to the cell culture or not. In conclusion, treatment with heparin lowers the kidney expression of proinflammatory mediators in B/W mice but does not affect nucleosomal activation of splenocytes. </p>","PeriodicalId":55254,"journal":{"name":"Clinical & Developmental Immunology","volume":" ","pages":"791262"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2013/791262","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40257675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of IL-33 in rheumatic diseases.","authors":"Lihua Duan, Jie Chen, Feili Gong, Guixiu Shi","doi":"10.1155/2013/924363","DOIUrl":"10.1155/2013/924363","url":null,"abstract":"<p><p>Interleukin-33 (IL-33), a novel member of IL-1 family, has been recently implicated in several inflammatory and autoimmune diseases. IL-33 can be produced by various types of tissues and cells and induce gene expression of Th2-associated cytokines via binding to the orphan receptor ST2. By promoting Th2 type immune response, IL-33 plays important roles in the allergy, whereas its function in autoimmune diseases attracts more attention. Recent studies reported the correlation of IL-33 with rheumatic diseases, and most of them found that the IL-33 expression levels were consistent with disease activity and development. Furthermore, evidence has indicated that IL-33-related treatment may ameliorate the pathogenic conditions and attenuate disease progression of those rheumatic diseases. Therefore, elucidation of the roles of IL-33 in rheumatic diseases would be beneficial to understand the pathogenesis and therapy of these diseases. In this paper, we will summarize the roles of IL-33 in the rheumatic diseases. </p>","PeriodicalId":55254,"journal":{"name":"Clinical & Developmental Immunology","volume":" ","pages":"924363"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2013/924363","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40257676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic and nonrenal adverse effects occurring in renal transplant patients treated with mTOR inhibitors.","authors":"Gianluigi Zaza,&nbsp;Paola Tomei,&nbsp;Paolo Ria,&nbsp;Simona Granata,&nbsp;Luigino Boschiero,&nbsp;Antonio Lupo","doi":"10.1155/2013/403280","DOIUrl":"https://doi.org/10.1155/2013/403280","url":null,"abstract":"<p><p>The mammalian target of rapamycin inhibitors (mTOR-I), sirolimus and everolimus, are immunosuppressive drugs largely used in renal transplantation. The main mechanism of action of these drugs is the inhibition of the mammalian target of rapamycin (mTOR), a regulatory protein kinase involved in lymphocyte proliferation. Additionally, the inhibition of the crosstalk among mTORC1, mTORC2, and PI3K confers the antineoplastic activities of these drugs. Because of their specific pharmacological characteristics and their relative lack of nephrotoxicity, these inhibitors are valid option to calcineurine inhibitors (CNIs) for maintenance immunosuppression in renal transplant recipients with chronic allograft nephropathy. However, as other immunosuppressive drugs, mTOR-I may induce the development of several adverse effects that need to be early recognized and treated to avoid severe illness in renal transplant patients. In particular, mTOR-I may induce systemic nonnephrological side effects including pulmonary toxicity, hematological disorders, dysmetabolism, lymphedema, stomatitis, cutaneous adverse effects, and fertility/gonadic toxicity. Although most of the adverse effects are dose related, it is extremely important for clinicians to early recognize them in order to reduce dosage or discontinue mTOR-I treatment avoiding the onset and development of severe clinical complications. </p>","PeriodicalId":55254,"journal":{"name":"Clinical & Developmental Immunology","volume":" ","pages":"403280"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2013/403280","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40259862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monocyte signal transduction receptors in active and latent tuberculosis.","authors":"Magdalena Druszczynska, Marcin Wlodarczyk, Beata Janiszewska-Drobinska, Grzegorz Kielnierowski, Joanna Zawadzka, Magdalena Kowalewicz-Kulbat, Marek Fol, Piotr Szpakowski, Karolina Rudnicka, Magdalena Chmiela, Wieslawa Rudnicka","doi":"10.1155/2013/851452","DOIUrl":"10.1155/2013/851452","url":null,"abstract":"<p><p>The mechanisms that promote either resistance or susceptibility to TB disease remain insufficiently understood. Our aim was to compare the expression of cell signaling transduction receptors, CD14, TLR2, CD206, and β2 integrin LFA-1 on monocytes from patients with active TB or nonmycobacterial lung disease and healthy individuals with M.tb latency and uninfected controls to explain the background of the differences between clinical and subclinical forms of M.tb infection. A simultaneous increase in the expression of the membrane bound mCD14 receptor and LFA-1 integrin in patients with active TB may be considered a prodrome of breaking immune control by M.tb bacilli in subjects with the latent TB and absence of clinical symptoms.</p>","PeriodicalId":55254,"journal":{"name":"Clinical & Developmental Immunology","volume":"2013 ","pages":"851452"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3562648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31323022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complement in human disease.","authors":"Michael A Flierl,&nbsp;Daniel Rittirsch,&nbsp;Markus S Huber-Lang,&nbsp;Philip F Stahel","doi":"10.1155/2013/920474","DOIUrl":"https://doi.org/10.1155/2013/920474","url":null,"abstract":"As part of innate immunity, the complement system embodies the “first line of defense” to various initial insults, including trauma, infection, hemorrhage, ischemia, and autoimmunity. While of beneficial intention, excessive complement activation can inadvertently damage healthy host tissues and thereby exacerbate the initial pathological events by causing an “innocent bystander effect.” \u0000 \u0000“Complementology” represents a rapidly evolving field. Recent scientific efforts have identified novel complement activation pathways and select complement-inhibiting compounds, which have been shown to ameliorate myriad autoimmune or inflammatory conditions. These findings have renewed the enthusiasm for novel pharmacological strategies targeting numerous inflammatory conditions, which currently elude successful transfer “from bench to bedside,” such as acute lung injury, sepsis, burn, ischemia-reperfusion injury, traumatic brain injury, and kidney disease. \u0000 \u0000The abundant involvement of the complement system in human health and disease is reflected by the wide range of topics covered in this special issue of Clinical and Developmental Immunology. \u0000 \u0000B. Nilsson and N. Ekdahl provide a summarizing article on current indications, techniques, sampling, and interpretations for clinical complement analyses. In addition, an easy-to-follow algorithm is provided for routine laboratory operations. \u0000 \u0000G. Cazander et al. illustrate the success of targeted complement inhibition of complement in wound healing and demonstrate how revesal of complement hyperactivity using several complement inhibitors has resulted in novel and innovative wound care strategies, which may soon be subject of clinical trials. \u0000 \u0000K. J. Welsh et al. challenge recent evidence that complement plays a critical role in the host defense against Mycobacterium tuberculosis. Following aerosol challenge with Mycobacterium tuberculosis, the authors demonstrate that “C7-knockout” mice had markedly reduced liver colony forming units and lung occlusion in conjunction with significantly increased total lymphocytes, decreased macrophages, and increased numbers of CD4+ cells. In line, expression of lung IFN-γ and TNF-α was increased in these animals, underscoring a crucial role of C7 in the disease manifestation of Mycobacterium tuberculosis. \u0000 \u0000S. R. Stowell et al.'s manuscript reviews the role of complement in transfusion-related mortality. This is of particular interest, as excessive complement activation during transfusion represents one of the most common features associated with fatality. The treating physician is furthermore provided with several strategies aiming to immunomodulate the complement system during incompatible red blood cell transfusions. \u0000 \u0000In two reviews, F. Bu et al. and S. F. Heeringa and colleagues review complement involvement in renal disease. Bu reviews the pathogenetic role of genetic variations in complement genes and complement dysregulation at the cell surface results in different","PeriodicalId":55254,"journal":{"name":"Clinical & Developmental Immunology","volume":"2013 ","pages":"920474"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2013/920474","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31323023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A review on JC virus infection in kidney transplant recipients.","authors":"Serena Delbue,&nbsp;Mariano Ferraresso,&nbsp;Luciana Ghio,&nbsp;Camilla Carloni,&nbsp;Silvia Carluccio,&nbsp;Mirco Belingheri,&nbsp;Alberto Edefonti,&nbsp;Pasquale Ferrante","doi":"10.1155/2013/926391","DOIUrl":"https://doi.org/10.1155/2013/926391","url":null,"abstract":"<p><p>The polyomavirus (PyV), JC virus (JCV), is a small nonenveloped DNA virus that asymptomatically infects about 80% of healthy adults and establishes latency in the kidney tissue. In case of immunodeficient hosts, JCV can lytically infect the oligodendrocytes, causing a fatal demyelinating disease, known as progressive multifocal leukoencephalopathy (PML). Although the reactivation of another human PyV, BK virus (BKV), is relatively common and its association with the polyomavirus associated nephropathy (PyVAN) following renal transplantation is proven, JCV replication and its impact on graft function and survival are less well studied. Here we describe the biology of JCV and its pathological features and we review the literature regarding the JCV infection analyzed in the setting of transplantations.</p>","PeriodicalId":55254,"journal":{"name":"Clinical & Developmental Immunology","volume":"2013 ","pages":"926391"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2013/926391","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31251903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How to translate basic knowledge into clinical application of biologic therapy in spondyloarthritis.","authors":"Chung-Tei Chou","doi":"10.1155/2013/369202","DOIUrl":"https://doi.org/10.1155/2013/369202","url":null,"abstract":"<p><p>Spondyloarthritis (SpA) is a family of many diseases, and these diseases share some clinical, genetic, and radiologic features. The disease process in the spine at the beginning is spinal inflammation, in which TNF α is the principal cytokine involved. Therefore, the dramatic clinical and pathologic response of anti-TNF α therapy in SpA is based upon the presence of increased TNF α in synovial tissues and sacroiliac joints, which perpetuates chronic inflammation. The increased Toll-like receptors (TCR) 2 and 4 in the serum, peripheral blood mononuclear cells, or synovial tissues of ankylosing spondyloarthritis (AS) or SpA patients suggest that SpA is highly associated with innate immunity. Any drug including anti-TNF α blocker which can downregulate the TCR, infiltrated neutrophils, or CD163+ macrophages in the synovial tissue is the rationale for the management of SpA. Like rheumatoid arthritis, the increased TH22 and TH17 cells either in blood, synovial fluid, or synovial tissues were also demonstrated in SpA. Thus, TH17 and TH22 may be reasonable cellular targets for therapeutic intervention. Drugs (anti-IL6R or anti-IL6) which can reduce the binding of IL6 and IL6R to the cell surface may be beneficial in SpA. Many proteins are implicated in the new bone formation (syndesmophyte) or ankylosis in AS or SpA. The enhanced BMP and Wnt pathway will activate osteoblasts which promote the new bone formation. However, no drug including anti-TNF α can stop or prevent the syndesmophyte in AS. In summary, looking for new targeting therapies for either anti-inflammation (beyond anti-TNF) or anti-bone formation (including anti-TGF β or PDGF) is warranted in the future. </p>","PeriodicalId":55254,"journal":{"name":"Clinical & Developmental Immunology","volume":"2013 ","pages":"369202"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2013/369202","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31212197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunogenetic study in Chinese population with ankylosing spondylitis: are there specific genes recently disclosed?","authors":"Jiayu Zhai,&nbsp;Ju Rong,&nbsp;Qiuxia Li,&nbsp;Jieruo Gu","doi":"10.1155/2013/419357","DOIUrl":"https://doi.org/10.1155/2013/419357","url":null,"abstract":"<p><strong>Purpose: </strong>Ankylosing spondylitis (AS) is a systemic, autoimmune disease resulting in the destruction of the affected joints. Over the past 5 years, several new genes or genetic regions associated with AS have been identified in the Chinese population. This paper aims to discuss the major findings and related potential mechanisms of these studies in our population.</p><p><strong>Recent findings: </strong>In recent years, due to the rapid advances in computational genetics and technology, there has been an increasing list of well-validated genes or genetic regions associated with AS susceptibility. So far, several genes or genetic regions have now been reported in the Han ethnic Chinese population, containing the major histocompatibility complex (MHC), ERAP1, IL-23R, 12q12, 2p15, 5q14.3, and so on. Different hypotheses for disease mechanisms have been investigated on the basis of the functional studies of these genes or genetic regions.</p><p><strong>Summary: </strong>This paper tries to summarize the association of several candidate genes with risk for AS in the Han ethnic Chinese population and aims to identify the novel inflammatory pathways and provide potential strategies for better therapies.</p>","PeriodicalId":55254,"journal":{"name":"Clinical & Developmental Immunology","volume":"2013 ","pages":"419357"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2013/419357","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31232412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conversion to sirolimus therapy in kidney transplant recipients with new onset diabetes mellitus after transplantation.","authors":"Massimiliano Veroux,&nbsp;Tiziano Tallarita,&nbsp;Daniela Corona,&nbsp;Nunziata Sinagra,&nbsp;Alessia Giaquinta,&nbsp;Domenico Zerbo,&nbsp;Carmela Guerrieri,&nbsp;Antonino D'Assoro,&nbsp;Sebastiano Cimino,&nbsp;Pierfrancesco Veroux","doi":"10.1155/2013/496974","DOIUrl":"https://doi.org/10.1155/2013/496974","url":null,"abstract":"<p><p>New-onset diabetes mellitus after transplantation (NODAT) may complicate 2-50% of kidney transplantation, and it is associated with reduced graft and patient survivals. In this retrospective study, we applied a conversion protocol to sirolimus in a cohort of kidney transplant recipients with NODAT. Among 344 kidney transplant recipients, 29 patients developed a NODAT (6.6%) and continued with a reduced dose of calcineurin inhibitors (CNI) (8 patients, Group A) or were converted to sirolimus (SIR) (21 patients, Group B). NODAT resolved in 37.5% and in 80% patients in Group A and Group B, respectively. In Group A, patient and graft survivals were 100% and 75%, respectively, not significantly different from Group B (83.4% and 68%, resp., P = 0.847). Graft function improved after conversion to sirolimus therapy: serum creatinine was 1.8 ± 0.7 mg/dL at the time of conversion and 1.6 ± 0.4 mg/dL five years after conversion to sirolimus therapy (P < 0.05), while in the group of patients remaining with a reduced dose of CNI, serum creatinine was 1.7 ± 0.6 mg/dL at the time of conversion and 1.65 ± 0.6 mg/dL at five-year followup (P = 0.732). This study demonstrated that the conversion from CNI to SIR in patients could improve significantly the metabolic parameters of patients with NODAT, without increasing the risk of acute graft rejection.</p>","PeriodicalId":55254,"journal":{"name":"Clinical & Developmental Immunology","volume":"2013 ","pages":"496974"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2013/496974","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31502452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}