Journal of Immunology Research The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. HLA-E: A Novel Player for Histocompatibility Mon, 20 Oct 2014 13:42:49 +0000 The classical class I human leukocyte antigens (HLA-A, -B, and -C) present allele-specific self- or pathogenic peptides originated by intracellular processing to CD8+ immune effector cells. Even a single mismatch in the heavy chain (hc) of an HLA class I molecule can impact on the peptide binding profile. Since HLA class I molecules are highly polymorphic and most of their polymorphisms affect the peptide binding region (PBR), it becomes obvious that systematic HLA matching is crucial in determining the outcome of transplantation. The opposite holds true for the nonclassical HLA class I molecule HLA-E. HLA-E polymorphism is restricted to two functional versions and is thought to present a limited set of highly conserved peptides derived from class I leader sequences. However, HLA-E appears to be a ligand for the innate and adaptive immune system, where the immunological response to peptide-HLA-E complexes is dictated through the sequence of the bound peptide. Structural investigations clearly demonstrate how subtle amino acid differences impact the strength and response of the cognate CD94/NKG2 or T cell receptor. Thomas Kraemer, Rainer Blasczyk, and Christina Bade-Doeding Copyright © 2014 Thomas Kraemer et al. All rights reserved. Immune Dysfunction in Rett Syndrome Patients Revealed by High Levels of Serum Anti-N(Glc) IgM Antibody Fraction Wed, 15 Oct 2014 06:54:13 +0000 Rett syndrome (RTT), a neurodevelopmental disorder affecting exclusively (99%) female infants, is associated with loss-of-function mutations in the gene encoding methyl-CpG binding protein 2 (MECP2) and, more rarely, cyclin-dependent kinase-like 5 (CDKL5) and forkhead box protein G1 (FOXG1). In this study, we aimed to evaluate the function of the immune system by measuring serum immunoglobulins (IgG and IgM) in RTT patients () and, by comparison, in age-matched children affected by non-RTT pervasive developmental disorders (non-RTT PDD) () and healthy age-matched controls (). To determine immunoglobulins we used both a conventional agglutination assay and a novel ELISA based on antibody recognition by a surrogate antigen probe, CSF114(Glc), a synthetic N-glucosylated peptide. Both assays provided evidence for an increase in IgM titer, but not in IgG, in RTT patients relative to both healthy controls and non-RTT PDD patients. The significant difference in IgM titers between RTT patients and healthy subjects in the CSF114(Glc) assay () suggests that this procedure specifically detects a fraction of IgM antibodies likely to be relevant for the RTT disease. These findings offer a new insight into the mechanism underlying the Rett disease as they unveil the possible involvement of the immune system in this pathology. Anna Maria Papini, Francesca Nuti, Feliciana Real-Fernandez, Giada Rossi, Caterina Tiberi, Giuseppina Sabatino, Shashank Pandey, Silvia Leoncini, Cinzia Signorini, Alessandra Pecorelli, Roberto Guerranti, Solange Lavielle, Lucia Ciccoli, Paolo Rovero, Claudio De Felice, and Joussef Hayek Copyright © 2014 Anna Maria Papini et al. All rights reserved. Alpha/Beta T-Cell Depleted Grafts as an Immunological Booster to Treat Graft Failure after Hematopoietic Stem Cell Transplantation with HLA-Matched Related and Unrelated Donors Mon, 13 Oct 2014 12:06:11 +0000 Allogeneic hematopoietic stem cell transplantation is associated with several complications and risk factors, for example, graft versus host disease (GVHD), viral infections, relapse, and graft rejection. While high levels of CD3+ cells in grafts can contribute to GVHD, they also promote the graft versus leukemia (GVL) effect. Infusions of extra lymphocytes from the original stem cell donor can be used as a treatment after transplantation for relapse or poor immune reconstitution but also they increase the risk for GVHD. In peripheral blood, 95% of T-cells express the T-cell receptor and the remaining T-cells express the T-cell receptor. As T-cells are the primary mediators of GVHD, depleting them from the graft should reduce this risk. In this pilot study, five patients transplanted with HLA-matched related and unrelated donors were treated with T-cell depleted stem cell boosts. The majority of T-cells in the grafts expressed and/or . Most patients receiving -depleted stem cell boosts increased their levels of white blood cells, platelets, and/or granulocytes 30 days after infusion. No signs of GVHD or other side effects were detected. A larger pool of patients with longer follow-up time is needed to confirm the data in this study. E. Rådestad, H. Wikell, M. Engström, E. Watz, B. Sundberg, S. Thunberg, M. Uzunel, J. Mattsson, and M. Uhlin Copyright © 2014 E. Rådestad et al. All rights reserved. Clinical Relevance of HLA Antibody Monitoring after Kidney Transplantation Mon, 13 Oct 2014 10:45:28 +0000 In kidney transplantation, antibody-mediated allograft injury caused by donor HLA-specific antibodies (DSA) has recently been identified as one of the major causes of late graft loss. This paper gives a brief overview on the impact of DSA development on graft outcome in organ transplantation with a focus on risk factors for de novo alloantibody induction and recently published guidelines for monitoring of DSA during the posttransplant phase. Christian Morath, Gerhard Opelz, Martin Zeier, and Caner Süsal Copyright © 2014 Christian Morath et al. All rights reserved. Immunomodulation by Trypanosoma cruzi: Toward Understanding the Association of Dendritic Cells with Infecting TcI and TcII Populations Mon, 13 Oct 2014 07:31:29 +0000 Dendritic cells (DCs) are major immune components, and depending on how these cells are modulated, the protective host immune response changes drastically. Trypanosoma cruzi is a parasite with high genetic variability and modulates DCs by interfering with their capacity for antigen recognition, migration, and maturation. Despite recent efforts, the association between DCs and T. cruzi I (TcI) and TcII populations is unknown. Herein, it was demonstrated that AQ1.7 and MUTUM TcI strains present low rates of invasion of bone marrow-derived DCs, whereas the 1849 and 2369 TcII strains present higher rates. Whereas the four strains similarly induced the expression of PD-L1, the production and expression of IL-10 and TLR-2, respectively, in DCs were differentially increased. The production of TNF-α, IL-12, IL-6, and CCL2 and the expression of CD40, CD80, MHC-II, CCR5, and CCR7 changed depending on the strain. The 2369 strain yielded the most remarkable results because greater invasion correlated with an increase in the levels of anti-inflammatory molecules IL-10 and PD-L1 but not with a change in the levels of TNF-α, MHC-II, or CD40 molecules. These results suggest that T. cruzi strains belonging to different populations have evolved specific evasion strategies that subvert DCs and consequently the host response. Thiago Alvares da Costa, Marcos Vinicius Silva, Maria Tays Mendes, Tamires Marielem Carvalho-Costa, Lara Rocha Batista, Eliane Lages-Silva, Virmondes Rodrigues, Carlo Jose Oliveira, and Luis Eduardo Ramirez Copyright © 2014 Thiago Alvares da Costa et al. All rights reserved. Effects of Awakening and the Use of Topical Dexamethasone and Levofloxacin on the Cytokine Levels in Tears Following Corneal Transplantation Sun, 12 Oct 2014 00:00:00 +0000 Objectives. To study the short-term effect of eye opening and use of topical dexamethasone phosphate 0.1% and levofloxacin 0.5% on the cytokine levels in human tears. Methods. Prospective experimental design was used for tear collection from eyes of 10 healthy controls and 20 patients four days after penetrating keratoplasty (PKP) at awakening and after instilling dexamethasone or levofloxacin. The concentrations of different cytokines were measured by cytometric bead array. Results. At eye opening, IL-6 levels were higher in the PKP group as compared to the controls. Thirty minutes later, the released levels of IL-10, IL-13, IL-17, IFNγ, and CCL5 increased in controls, while CXCL8 decreased in both control and PKP groups. The release of the cytokines remained stable after 30 mins except for IFNγ, which showed a decrease in the controls following levofloxacin instillation. No short-term effects of the topically used dexamethasone and levofloxacin could be detected on the cytokine levels in controls and after PKP. Conclusions. Evidence of changes in the levels and time course of tear cytokines after awakening or eye opening could be established and the short-term confounding effects of dexamethasone and levofloxacin on the levels of released cytokines in human tears could be excluded. Mariann Fodor, Goran Petrovski, Dorottya Pásztor, Péter Gogolák, Éva Rajnavölgyi, and András Berta Copyright © 2014 Mariann Fodor et al. All rights reserved. Immune and Inflammatory Processes in Obesity, Insulin Resistance, Diabetes, and Related Cardiometabolic Complications Sun, 21 Sep 2014 10:57:48 +0000 Joseph Fomusi Ndisang, Sharad Rastogi, and Alfredo Vannacci Copyright © 2014 Joseph Fomusi Ndisang et al. All rights reserved. Powering the Immune System: Mitochondria in Immune Function and Deficiency Sun, 21 Sep 2014 06:18:15 +0000 Mitochondria are critical subcellular organelles that are required for several metabolic processes, including oxidative phosphorylation, as well as signaling and tissue-specific processes. Current understanding of the role of mitochondria in both the innate and adaptive immune systems is expanding. Concurrently, immunodeficiencies arising from perturbation of mitochondrial elements are increasingly recognized. Recent observations of immune dysfunction and increased incidence of infection in patients with primary mitochondrial disorders further support an important role for mitochondria in the proper function of the immune system. Here we review current findings. Melissa A. Walker, Stefano Volpi, Katherine B. Sims, Jolan E. Walter, and Elisabetta Traggiai Copyright © 2014 Melissa A. Walker et al. All rights reserved. The Central Role of the Gut Microbiota in Chronic Inflammatory Diseases Thu, 18 Sep 2014 11:09:08 +0000 The commensal microbiota is in constant interaction with the immune system, teaching immune cells to respond to antigens. Studies in mice have demonstrated that manipulation of the intestinal microbiota alters host immune cell homeostasis. Additionally, metagenomic-sequencing analysis has revealed alterations in intestinal microbiota in patients suffering from inflammatory bowel disease, asthma, and obesity. Perturbations in the microbiota composition result in a deficient immune response and impaired tolerance to commensal microorganisms. Due to altered microbiota composition which is associated to some inflammatory diseases, several strategies, such as the administration of probiotics, diet, and antibiotic usage, have been utilized to prevent or ameliorate chronic inflammatory diseases. The purpose of this review is to present and discuss recent evidence showing that the gut microbiota controls immune system function and onset, development, and resolution of some common inflammatory diseases. Caroline Marcantonio Ferreira, Angélica Thomaz Vieira, Marco Aurelio Ramirez Vinolo, Fernando A. Oliveira, Rui Curi, and Flaviano dos Santos Martins Copyright © 2014 Caroline Marcantonio Ferreira et al. All rights reserved. Association of Helicobacter pylori and iNOS Production by Macrophages and Lymphocytes in the Gastric Mucosa in Chronic Gastritis Thu, 18 Sep 2014 09:11:48 +0000 Helicobacter pylori is one of the most common causes of chronic gastritis. With the development of the disease cellular inflammatory infiltrates composed of lymphocytes, plasma cells, and macrophages are formed in epithelium and lamina propria of the stomach. These cells are capable of secreting a number of active substances, including inducible nitric oxide synthase (iNOS). We examined the relationship between H. pylori and secretion of iNOS by cells of inflammatory infiltrates in chronic gastritis by light microscopy and immunohistochemistry. The data obtained indicate that stimulation of H. pylori immune system cells of the host organism during development of chronic gastritis causes increase in number of macrophages and lymphocytes in the inflammatory infiltrate of the gastric mucosa. This is accompanied with increased expression of inducible NO-synthase with excess free radicals in the tissues, which leads to secondary alterations and exacerbates the inflammation with impaired regeneration processes. Lilia A. Cherdantseva, Oksana V. Potapova, Tatyana V. Sharkova, Yana Yu. Belyaeva, and Vyacheslav A. Shkurupiy Copyright © 2014 Lilia A. Cherdantseva et al. All rights reserved. The Impact of “Omic” and Imaging Technologies on Assessing the Host Immune Response to Biodefence Agents Tue, 16 Sep 2014 08:33:18 +0000 Understanding the interactions between host and pathogen is important for the development and assessment of medical countermeasures to infectious agents, including potential biodefence pathogens such as Bacillus anthracis, Ebola virus, and Francisella tularensis. This review focuses on technological advances which allow this interaction to be studied in much greater detail. Namely, the use of “omic” technologies (next generation sequencing, DNA, and protein microarrays) for dissecting the underlying host response to infection at the molecular level; optical imaging techniques (flow cytometry and fluorescence microscopy) for assessing cellular responses to infection; and biophotonic imaging for visualising the infectious disease process. All of these technologies hold great promise for important breakthroughs in the rational development of vaccines and therapeutics for biodefence agents. Julia A. Tree, Helen Flick-Smith, Michael J. Elmore, and Caroline A. Rowland Copyright © 2014. All rights reserved. The Role of Inflammatory, Anti-Inflammatory, and Regulatory Cytokines in Patients Infected with Cutaneous Leishmaniasis in Amazonas State, Brazil Thu, 11 Sep 2014 09:45:26 +0000 The authors discuss in this paper the role of inflammatory, anti-inflammatory, and regulatory cytokines in patients infected with different species of Leishmania in Amazonas State, Brazil. A comparative analysis was made of serum concentrations of these cytokines in the peripheral blood of 33 patients infected with cutaneous leishmaniasis. The isolates were identified as Leishmania guyanensis, L. naiffi, and L. amazonensis. Most (64%) of the patients were male ranging in age from 18 to 58 years. Protein expression profiles of IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α, and IL-17 cytokines were shown to vary significantly between infected and noninfected (control group) individuals and according to the Leishmania species. Infection caused by L. guyanensis accounted for 73% of the cases and patients with this parasite also showed higher concentrations of IL-2, IFN-γ, IL-4, and IL-17 when compared to infection by L. amazonensis. Patients with infection caused by L. naiffi showed higher concentration of the cytokines analyzed when compared to uninfected patients; however, there was no statistically significant difference with the other species analyzed. Thaís Tibery Espir, Luanda de Paula Figueira, Maricleide de Farias Naiff, Allyson Guimarães da Costa, Marcelo Ramalho-Ortigão, Adriana Malheiro, and Antonia Maria Ramos Franco Copyright © 2014 Thaís Tibery Espir et al. All rights reserved. Comparisons of CVID and IgGSD: Referring Physicians, Autoimmune Conditions, Pneumovax Reactivity, Immunoglobulin Levels, Blood Lymphocyte Subsets, and HLA-A and -B Typing in 432 Adult Index Patients Thu, 11 Sep 2014 08:29:32 +0000 Common variable immunodeficiency (CVID) and immunoglobulin (Ig) G subclass deficiency (IgGSD) are heterogeneous disorders characterized by respiratory tract infections, selective Ig isotype deficiencies, and impaired antibody responses to polysaccharide antigens. Using univariable analyses, we compared observations in 34 CVID and 398 IgGSD adult index patients (81.9% women) referred to a hematology/oncology practice. Similarities included specialties of referring physicians, mean ages, proportions of women, reactivity to Pneumovax, median serum IgG3 and IgG4 levels, median blood CD56+/CD16+ lymphocyte levels, positivity for HLA-A and -B types, and frequencies of selected HLA-A, -B haplotypes. Dissimilarities included greater prevalence of autoimmune conditions, lower median IgG, IgA, and IgM, and lower median CD19+, CD3+/CD4+, and CD3+/CD8+ blood lymphocytes in CVID patients. Prevalence of Sjögren’s syndrome and hypothyroidism was significantly greater in CVID patients. Combined subnormal IgG1/IgG3 occurred in 59% and 29% of CVID and IgGSD patients, respectively. Isolated subnormal IgG3 occurred in 121 IgGSD patients (88% women). Logistic regression on CVID (versus IgGSD) revealed a significant positive association with autoimmune conditions and significant negative associations with IgG1, IgG3, and IgA and CD56+/CD16+ lymphocyte levels, but the odds ratio was increased for autoimmune conditions alone (6.9 (95% CI 1.3, 35.5)). James C. Barton, Luigi F. Bertoli, and J. Clayborn Barton Copyright © 2014 James C. Barton et al. All rights reserved. Pathophysiological Roles of Cytokine-Chemokine Immune Network Thu, 11 Sep 2014 07:27:43 +0000 Jong-Young Kwak, Mizuko Mamura, Jana Barlic-Dicen, and Evelin Grage-Griebenow Copyright © 2014 Jong-Young Kwak et al. All rights reserved. Cytokine-Mediated Bone Destruction in Rheumatoid Arthritis Wed, 10 Sep 2014 07:51:16 +0000 Bone homeostasis, which involves formation and resorption, is an important process for maintaining adequate bone mass in humans. Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation and bone loss, leading to joint destruction and deformity, and is a representative disease of disrupted bone homeostasis. The bone loss and joint destruction are mediated by immunological insults by proinflammatory cytokines and various immune cells. The connection between bone and immunity has been intensely studied and comprises the emerging field of osteoimmunology. Osteoimmunology is an interdisciplinary science investigating the interplay between the skeletal and the immune systems. The main contributors in osteoimmunology are the bone effector cells, such as osteoclasts or osteoblasts, and the immune cells, particularly lymphocytes and monocytes. Physiologically, osteoclasts originate from immune cells, and immune cells regulate osteoblasts and vice versa. Pathological conditions such as RA might affect these interactions, thereby altering bone homeostasis, resulting in the unfavorable outcome of bone destruction. In this review, we describe the osteoclastogenic roles of the proinflammatory cytokines and immune cells that are important in the pathophysiology of RA. Seung Min Jung, Kyoung Woon Kim, Chul-Woo Yang, Sung-Hwan Park, and Ji Hyeon Ju Copyright © 2014 Seung Min Jung et al. All rights reserved. Immunological Aspects of Acute and Recurrent Herpes Simplex Keratitis Sun, 07 Sep 2014 11:41:18 +0000 Herpes simplex keratitis (HSK) belongs to the major causes of visual morbidity worldwide and available methods of treatment remain unsatisfactory. Primary infection occurs usually early in life and is often asymptomatic. Chronic visual impairment and visual loss are caused by corneal scaring, thinning, and vascularization connected with recurrent HSV infections. The pathogenesis of herpetic keratitis is complex and is still not fully understood. According to the current knowledge, corneal scarring and vascularization are the result of chronic inflammatory reaction against HSV antigens. In this review we discuss the role of innate and adaptive immunities in acute and recurrent HSV ocular infection and present the potential future targets for novel therapeutical options based on immune interventions. Jacek Rolinski and Iwona Hus Copyright © 2014 Jacek Rolinski and Iwona Hus. All rights reserved. Complement System in Pathogenesis of AMD: Dual Player in Degeneration and Protection of Retinal Tissue Thu, 04 Sep 2014 00:00:00 +0000 Age-related macular degeneration (AMD) is the most common cause of blindness among the elderly, especially in Western countries. Although the prevalence, risk factors, and clinical course of the disease are well described, its pathogenesis is not entirely elucidated. AMD is associated with a variety of biochemical abnormalities, including complement components deposition in the retinal pigment epithelium-Bruch’s membrane-choriocapillaris complex. Although the complement system (CS) is increasingly recognized as mediating important roles in retinal biology, its particular role in AMD pathogenesis has not been precisely defined. Unrestricted activation of the CS following injury may directly damage retinal tissue and recruit immune cells to the vicinity of active complement cascades, therefore detrimentally causing bystander damage to surrounding cells and tissues. On the other hand, recent evidence supports the notion that an active complement pathway is a necessity for the normal maintenance of the neurosensory retina. In this scenario, complement activation appears to have beneficial effect as it promotes cell survival and tissue remodeling by facilitating the rapid removal of dying cells and resulting cellular debris, thus demonstrating anti-inflammatory and neuroprotective activities. In this review, we discuss both the beneficial and detrimental roles of CS in degenerative retina, focusing on the diverse aspects of CS functions that may promote or inhibit macular disease. Milosz P. Kawa, Anna Machalinska, Dorota Roginska, and Boguslaw Machalinski Copyright © 2014 Milosz P. Kawa et al. All rights reserved. A Simple Method for Establishing Adherent Ex Vivo Explant Cultures from Human Eye Pathologies for Use in Subsequent Calcium Imaging and Inflammatory Studies Thu, 04 Sep 2014 00:00:00 +0000 A novel, simple, and reproducible method for cultivating pathological tissues obtained from human eyes during surgery was developed using viscoelastic material as a tissue adherent to facilitate cell attachment and expansion and calcium imaging of cultured cells challenged by mechanical and acetylcholine (ACh) stimulation as well as inflammatory studies. Anterior lens capsule-lens epithelial cells (aLC-LECs) from cataract surgery and proliferative diabetic retinopathy (PDR) fibrovascular epiretinal membranes (fvERMs) from human eyes were used in the study. We hereby show calcium signaling in aLC-LECs by mechanical and acetylcholine (ACh) stimulation and indicate presence of ACh receptors in these cells. Furthermore, an ex vivo study model was established for measuring the inflammatory response in fvERMs and aLC-LECs upon TNFα treatment. Sofija Andjelic, Xhevat Lumi, Zoltán Veréb, Natasha Josifovska, Andrea Facskó, Marko Hawlina, and Goran Petrovski Copyright © 2014 Sofija Andjelic et al. All rights reserved. Current Status for Gastrointestinal Nematode Diagnosis in Small Ruminants: Where Are We and Where Are We Going? Tue, 02 Sep 2014 09:02:13 +0000 Gastrointestinal nematode (GIN) parasites pose a significant economic burden particularly in small ruminant production systems. Anthelmintic resistance is a serious concern to the effective control of GIN parasites and has fuelled the focus to design and promote sustainable control of practices of parasite control. Many facets of sustainable GIN parasite control programs rely on the ability to diagnose infection both qualitatively and quantitatively. Diagnostics are required to determine anthelmintic efficacies, for targeted treatment programs and selection of animals for parasite resistant breeding. This review describes much of the research investigated to date to improve the current diagnostic for the above practices which is based on counting the number of parasite eggs in faeces. Sarah Jane Margaret Preston, Mark Sandeman, Jorge Gonzalez, and David Piedrafita Copyright © 2014 Sarah Jane Margaret Preston et al. All rights reserved. T Cells Immunology in the Immunological Diseases Mon, 01 Sep 2014 08:47:56 +0000 Xiuli Wu, Grzegorz K. Przybylski, Qintai Yang, and Qifa Liu Copyright © 2014 Xiuli Wu et al. All rights reserved. Soluble HLA Technology as a Strategy to Evaluate the Impact of HLA Mismatches Mon, 01 Sep 2014 07:22:41 +0000 HLA class I incompatibilities still remain one of the main barriers for unrelated bone marrow transplantation (BMT); hence the molecular understanding of how to mismatch patients and donors and still have successful clinical outcomes will guide towards the future of unrelated BMT. One way to estimate the magnitude of polymorphisms within the PBR is to determine which peptides can be selected by individual HLA alleles and subsequently presented for recognition by T cells. The features (structure, length, and sequence) of different peptides each confer an individual pHLA landscape and thus directly shape the individual immune response. The elution and sequencing of peptides by mass spectrometric analysis enable determining the bona fide repertoire of presented peptides for a given allele. This is an effective and simple way to compare the functions of allelic variants and make a first assessment of their degree of permissivity. We describe the methodology used for peptide sequencing and the limitations of peptide prediction tools compared to experimental methods. We highlight the altered peptide features that are observed between allelic variants and the need to discover the altered peptide repertoire in situations of “artificial” graft versus host disease (GvHD) that occur in HLA-specific hypersensitive immune responses to drugs. Heike Kunze-Schumacher, Rainer Blasczyk, and Christina Bade-Doeding Copyright © 2014 Heike Kunze-Schumacher et al. All rights reserved. OCH Ameliorates Bone Marrow Failure in Mice via Downregulation of T-Bet Expression Thu, 28 Aug 2014 09:46:24 +0000 The aim of this study is to evaluate the immune mechanism of OCH in the treatment of AA (also named bone marrow failure, BMF) induced in mice. OCH at a dose of 400 μg/kg was injected intraperitoneally (I.P.) prior to the induction of BMF. Our study showed that the incidence of BMF was 100% in BMF group and 13% in OCH treatment group. Significant higher level of IL-4 and lower level of IFN-γ were observed in OCH group than that in BMF group () as well as untreated group over BMF (). However, there was no significant difference between OCH and untreated group. Compared with untreated, the expression level of T-bet in OCH and BMF was all significantly higher. However, T-bet expression level was lower in OCH than in BMF. In addition, OCH treatment increased NKT cell fractions of bone marrow and the colonies of CFU-GM. In conclusion, treatment of OCH prior to the induction of BMF could prevent the incidence of BMF possibly through downregulating T-bet expression leading to the transition of immune response from Th1 to Th2, suggesting OCH might be a new therapeutic approach in the treatment of BMF or AA. Xiaohong Qiao, Xiaotian Xie, Wei Shi, Jinqing Tang, Yuexia Shao, and Fuxing Li Copyright © 2014 Xiaohong Qiao et al. All rights reserved. Clinical Biomarkers and Pathogenic-Related Cytokines in Rheumatoid Arthritis Thu, 21 Aug 2014 09:16:34 +0000 Rheumatoid arthritis (RA) is a common autoimmune disease with unknown etiology and pathogenesis. Although major therapeutic advances have been made in recent years, there is no cure for the disease. Current medications mainly reduce inflammation in order to relieve pain and slow joint damage, but many have potentially serious side effects. Therefore, to find specific biomarkers will benefit both RA patients to find relief from the disease and physicians to monitor the disease development. A number of biomarkers have been discovered and used clinically, and others are still under investigation. The autoantibodies, which are widely used in diagnosis and prognosis, novel biomarkers, which reflect clinical disease activity, and newly found biomarkers and pathogenic-related cytokines are discussed in this review. Xiaoyin Niu and Guangjie Chen Copyright © 2014 Xiaoyin Niu and Guangjie Chen. All rights reserved. Cancer Immunology and Cancer Immunodiagnosis Thu, 21 Aug 2014 07:38:23 +0000 Jianying Zhang, Suxia Han, Bin Zhang, and Yi Zhang Copyright © 2014 Jianying Zhang et al. All rights reserved. Clinical Features and Genetic Analysis of 20 Chinese Patients with X-Linked Hyper-IgM Syndrome Wed, 20 Aug 2014 07:29:49 +0000 X-linked hyper-IgM syndrome (XHIGM) is one type of primary immunodeficiency diseases, resulting from defects in the CD40 ligand/CD40 signaling pathways. We retrospectively analyzed the clinical and molecular features of 20 Chinese patients diagnosed and followed up in hospitals affiliated to Shanghai Jiao Tong University School of Medicine from 1999 to 2013. The median onset age of these patients was 8.5 months (range: 20 days–21 months). Half of them had positive family histories, with a shorter diagnosis lag. The most common symptoms were recurrent sinopulmonary infections (18 patients, 90%), neutropenia (14 patients, 70%), oral ulcer (13 patients, 65%), and protracted diarrhea (13 patients, 65%). Six patients had BCGitis. Six patients received hematopoietic stem cell transplantations and four of them had immune reconstructions and clinical remissions. Eighteen unique mutations in CD40L gene were identified in these 20 patients from 19 unrelated families, with 12 novel mutations. We compared with reported mutation results and used bioinformatics software to predict the effects of mutations on the target protein. These mutations reflected the heterogeneity of CD40L gene and expanded our understanding of XHIGM. Lin-Lin Wang, Wei Zhou, Wei Zhao, Zhi-Qing Tian, Wei-Fan Wang, Xiao-Fang Wang, and Tong-Xin Chen Copyright © 2014 Lin-Lin Wang et al. All rights reserved. Cytokine Network Involvement in Subjects Exposed to Benzene Mon, 18 Aug 2014 09:13:49 +0000 Benzene represents an ubiquitous pollutant both in the workplace and in the general environment. Health risk and stress posed by benzene have long been a concern because of the carcinogenic effects of the compound which was classified as a Group 1 carcinogen to humans and animals. There is a close correlation between leukemia, especially acute myeloid leukemia, and benzene exposure. In addition, exposure to benzene can cause harmful effects on immunological, neurological, and reproductive systems. Benzene can directly damage hematopoietic progenitor cells, which in turn could lead to apoptosis or may decrease responsiveness to cytokines and cellular adhesion molecules. Alternatively, benzene toxicity to stromal cells or mature blood cells could disrupt the regulation of hematopoiesis, including hematopoietic commitment, maturation, or mobilization, through the network of cytokines, chemokines, and adhesion molecules. Today there is mounting evidence that benzene may alter the gene expression, production, or processing of several cytokines in vitro and in vivo. The purpose of this review was to systematically analyze the published cases of cytokine effects on human benzene exposure, particularly hematotoxicity, and atopy, and on lungs. Paola Lucia Minciullo, Michele Navarra, Gioacchino Calapai, and Sebastiano Gangemi Copyright © 2014 Paola Lucia Minciullo et al. All rights reserved. Antiphospholipid Syndrome and Antibodies Mon, 18 Aug 2014 08:47:40 +0000 Jozélio Freire de Carvalho, Roger Abramino Levy, and Yehuda Shoenfeld Copyright © 2014 Jozélio Freire de Carvalho et al. All rights reserved. Appropriate Development of the Liver Treg Compartment Is Modulated by the Microbiota and Requires TGF-β and MyD88 Thu, 07 Aug 2014 09:00:14 +0000 Neither the early postnatal development of the liver Treg compartment nor the factors that regulate its development has been characterized. We compared the early developmental patterns of Treg cell accumulation in murine liver, thymus, and spleen. A FoxP3EGFP reporter mouse was employed to identify Treg cells. Mononuclear cells were isolated from organs postnatally, stained for CD4, and examined by flow cytometry to enumerate FoxP3+ cells. To assess roles for TGF-, MyD88, and TLR2, gene-specific knockout pups were generated from heterozygous breeders. To test the role of commensal bacteria, pregnant dams were administered antibiotics during gestation and after parturition. The pattern of appearance of Treg cells differed in liver, spleen, and thymus. Notably, at 1-2 weeks, the frequency of FoxP3+ T cells in liver exceeded that in spleen by 1.5- to 2-fold. The relative increase in liver Treg frequency was transient and was dependent upon TGF- and MyD88, but not TLR2, and was abrogated by antibiotic treatment. A relative increase in liver Treg frequency occurs approximately 1-2 weeks after parturition that appears to be driven by colonization of the intestine with commensal bacteria and is mediated by a pathway that requires TGF- and MyD88, but not TLR2. Ann Maria, Kathryn A. English, and James D. Gorham Copyright © 2014 Ann Maria et al. All rights reserved. The Role of Chemokines in Breast Cancer Pathology and Its Possible Use as Therapeutic Targets Tue, 05 Aug 2014 10:57:25 +0000 Chemokines are small proteins that primarily regulate the traffic of leukocytes under homeostatic conditions and during specific immune responses. The chemokine-chemokine receptor system comprises almost 50 chemokines and approximately 20 chemokine receptors; thus, there is no unique ligand for each receptor and the binding of different chemokines to the same receptor might have disparate effects. Complicating the system further, these effects depend on the cellular milieu. In cancer, although chemokines are associated primarily with the generation of a protumoral microenvironment and organ-directed metastasis, they also mediate other phenomena related to disease progression, such as angiogenesis and even chemoresistance. Therefore, the chemokine system is becoming a target in cancer therapeutics. We review the emerging data and correlations between chemokines/chemokine receptors and breast cancer, their implications in cancer progression, and possible therapeutic strategies that exploit the chemokine system. M. Isabel Palacios-Arreola, Karen E. Nava-Castro, Julieta I. Castro, Eduardo García-Zepeda, Julio C. Carrero, and Jorge Morales-Montor Copyright © 2014 M. Isabel Palacios-Arreola et al. All rights reserved. Congenital Defects in Neutrophil Dynamics Tue, 05 Aug 2014 08:13:53 +0000 Neutrophil granulocytes are key effector cells of the vertebrate immune system. They represent 50–70% of the leukocytes in the human blood and their loss by disease or drug side effect causes devastating bacterial infections. Their high turnover rate, their fine-tuned killing machinery, and their arsenal of toxic vesicles leave them particularly vulnerable to various genetic deficiencies. The aim of this review is to highlight those congenital immunodeficiencies which impede the dynamics of neutrophils, such as migration, cytoskeletal rearrangements, vesicular trafficking, and secretion. Marton Keszei and Lisa S. Westerberg Copyright © 2014 Marton Keszei and Lisa S. Westerberg. All rights reserved.