University Children's Hospital Muenster, Pediatric Hematology and Oncology, Albert-Schweitzer Campus 1, Building A1, 48149 Muenster, Germany. Electronic address:
Chimeric T cell receptors (CARs) combine extracellular antigen recognition domains and T cell activation components in single molecules. CAR gene transfer thereby allows to generate T cells with engineered specificities. The translational development of CAR-based T cell therapies is most advanced in B cell cancers where CAR-engineered T cells against the B lineage antigen CD19 have generated impressive results in early clinical trials. Read More
Division of Rheumatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States. Electronic address:
Interstitial lung disease (ILD) in the connective tissue diseases (CTD) is amongst the most challenging aspect of care of patients with rheumatic diseases and is the source of significant morbidity and mortality. While there has been progress in our understanding of the natural history of these complications, we still suffer from a limited reservoir of data to confidently determine which patients are at highest risk for disease and those who are at highest risk for disease progression. Treatment options until recently have been limited to anti-inflammatory therapies but with the emerging availability of anti-fibrotic therapies, a shift in strategy is emerging to target therapies based on the specific radiographic, histopathologic features and biomarker profiles that are unique to patients with rheumatic diseases and ILD. Read More
Department of Pediatric Rheumatology and Immunology, University Hospital Muenster, Germany.
Objective: To characterize peripheral blood monocytes in uveitis associated with juvenile idiopathic arthritis (JIAU).
Methods: Peripheral blood monocytes from children with JIA (either with (n=18) or without uveitis (n=11)), idiopathic anterior uveitis (IAU; n=12) and healthy controls (n=11) were analyzed by flow cytometry.
Results: Percentage of CD14+CD86+ monocytes and CD86 expression on single cell level were significantly higher in all patient groups than in controls, whereas no major differences existed between patient groups. Read More
Department of Physiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Citrullinated alpha enolase (CEP-1) has been designated as a major antigenic target of antibodies against citrullinated proteins (ACPA) in patients with rheumatoid arthritis (RA). Our aim is to determine the prevalence of anti-CEP-1 in a cohort of ACPA positive (ACPA+) primary Sjogren's syndrome (pSS) patients. Anti-CEP1 titers were determined by ELISA in sera from 15 ACPA+ and 45 ACPA- age/sex matched pSS; 12 ACPA+ RA patients and 30 healthy controls (HC). Read More
Department of Medicine, Rheumatology Unit, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Natural IgM autoantibodies have been proposed to convey protection from autoimmune pathogenesis. Herein, we investigated the IgM responses in 396 systemic lupus erythematosus (SLE) patients, divided into subgroups based on distinct autoantibody profiles. Depressed IgM levels were more common in SLE than in matched population controls. Read More
University Department of Pediatrics, Unit of Immune and Infectious Diseases, Childrens' Hospital Bambino Gesù, Italy; Crs4, Biomedicine, Pula, CA, Italy; IRGB CNR, Cittadella Universitaria, Monserrato, CA, Italy; University Department of Pediatrics, Endocrinology Unit, Childrens' Hospital Bambino Gesù, Italy; Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy. Electronic address:
b Allergy Immunology and Blood and Marrow Transplant Division , University of California San Francisco, Benioff Children's Hospital , San Francisco , CA.
Introduction: Newborn screening has led to a better understanding of the prevalence of Severe Combined Immunodeficiency (SCID) overall and in terms of specific genotypes. Survival has improved following hematopoietic stem cell transplantation (HCT) with the best outcomes seen following use of a matched sibling donor. However, questions remain regarding the optimal alternative donor source, appropriate use of conditioning and the impact of these decisions on immune reconstitution and other late morbidities. Read More
a University Children's Hospital, University of Wuerzburg , Josef-Schneider-Str. 2, 97080 Wuerzburg Germany.
Introduction: Ureaplasma species (spp.) have been acknowledged as major causative pathogens in chorioamnionitis and prematurity, but may also contribute to key morbidities in preterm infants. Several epidemiological and experimental data indicate an association of neonatal Ureaplasma colonization and/or infection with bronchopulmonary dysplasia. Read More
Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Otorhinolaryngology Institute, Sun Yat-sen University, Guangzhou 510080, China. Electronic address:
Group 2 innate lymphoid cells (ILC2s) are essential in initiating and driving allergic immune responses. However, there were inconsistent findings of the ILC2 levels in allergic rhinitis (AR) patients. This study investigated the ILC2 levels in the peripheral blood of house dust mite (HDM)-allergic AR patients and their ability to secrete type 2 cytokines. Read More
Department of Medicine B, Allergy, Clinical Immunology and AIDS Center, Kaplan Medical Center, Rehovot, Israel. Electronic address:
Introduction: Semaphorin-4D (CD100), generated by CD4/CD8 cells, plays an important role in T cells activation. It also regulates B cell differentiation via its receptor the CD72. Both have soluble forms - sCD100/sCD72. Read More
JAK3 is a tyrosine kinase essential for signaling downstream of the common gamma chain subunit shared by multiple cytokine receptors. JAK3 deficiency results in T(-)B(+)NK(-) severe combined immune deficiency (SCID). We report a patient with SCID due to a novel mutation in the JAK3 JH4 domain. Read More
Department of Pathogenic Biology and Immunology, Guangzhou Hoffmann Institute of Immunology, School of Basic Sciences, Guangzhou Medical University, Guangzhou 510182, China; Department of Cancer Immunology and Virology, Dana Farber Cancer Institute, Boston, MA 02115, USA. Electronic address:
Acute myeloid leukemia (AML) is one of the most common types of leukemia among adults with an overall poor prognosis and very limited treatment management. Immune checkpoint blockade of PD-1 alone or combined with other immune checkpoint blockade has gained impressive results in murine AML models by improving anti-leukemia CD8(+)T cell function, which has greatly promoted the strategy to utilize combined immune checkpoint inhibitors to treat AML patients. However, the expression profiles of these inhibitory receptors in T cells from AML patients have not been clearly defined. Read More
Introduction: Non-steroidal anti-inflammatory drugs (NSAIDs) are the most frequently involved in drug hypersensitivity reactions (DHR). NSAIDs are prescribed for different processes and some NSAIDs can be obtained over the counter. Areas covered: We analyse the practical approaches for managing and treating NSAID-DHR considering the five major groups of entities recognised, divided into two categories: those responding to strong COX-1 inhibitors and possibly weak COX-1 or selective COX-2 inhibitors named cross-intolerant (CI), and those induced by a single drug or drug group with good tolerance to strong COX-1 inhibitors, known as allergic reactions (SR). Read More
The role and significance of interleukin (IL)-21 in the development of sporadic CRC have not been well defined. The aim of this study is therefore to investigate the dynamics of the IL-21 along colorectal adenoma-carcinoma sequence and to evaluate the impact of IL-21 on clinicopathological parameters and CRC prognosis. The real-time PCR results showed that the level of IL-21 in adenomas (n=50) and sporadic CRC (n=50) were significantly higher than that in normal controls (n=18), which were predominately observed in the adenoma/CRC stroma. Read More
Persistent stimulation with antigens derived from viruses that establish chronic infections or tumour antigens results in the exhaustion of T cells. Coinhibitory receptors like PD-1 and CTLA-4 function as immune checkpoints on exhausted T cells. Blocking these molecules with antibodies improve immunity to cancer cells. Read More
Centre for Immune Regulation and Reproductive Immunology (CIRRI), Department of Clinical Biochemistry, Zealand University Hospital, DK-4000 Roskilde, Denmark; Department of Clinical Medicine, University of Copenhagen, Denmark. Electronic address:
HLA class Ia (HLA-ABC) and HLA class Ib (HLA-E, -F and -G) molecules and FOXP3+ tumor-infiltrating lymphocytes (TILs) are often reported as relevant factors of tumor immune regulation. We investigated their expression as prognostic factors in 200 patients with primary cutaneous melanoma (PCM). In our cohort, patients with tumors showing upregulation of HLA-ABC molecules had significantly thicker tumors (32% vs 7%, P<0. Read More
Anti-citrullinated Protein Antibodies (ACPA) are excellent markers for Rheumatoid arthritis (RA) and are postulated to have a pathogenic role in the disease process. A multistep model for the evolution of the ACPA response in RA was proposed in which an initial break of tolerance causes, as "first hit", "silent" production of ACPA without any clinical symptoms. The model further proposes that the ACPA immune response matures upon a certain (unknown) trigger, a "second hit", which leads to epitope spreading, an increase in ACPA titres and extended isotype usage before clinical RA manifestations. Read More
Dendritic cells (DCs) are bone-marrow-derived immune cells accounted for a key role in cancer vaccination as potent antigen-presenting cells within the immune system. Cancer microenvironment can modulate DCs maturation resulting in their accumulation into functional states associated with a reduced antitumor immune response. In this regard, a successful cancer vaccine needs to mount a potent antitumor immune response able to overcome the immunosuppressive tumor milieu. Read More
Background: Biological drugs, mainly interleukin (IL)-1 and IL-6 antagonists, but also tumor necrosis factor (TNF) inhibitors, have been used in the treatment of adult onset Still's disease patients (AOSD).
Research Design And Methods: We summarised the available evidence for the effectiveness of biologic drugs in AOSD. A systematic review of the literature was performed in order to identify all the available data concerning the effectiveness of biologic drugs in AOSD. Read More
Small molecules interfering with intracellular signalling pathways are used in the treatment of multiple diseases including RA. However, small molecules usually affect signalling in most cell types, not only in those which need to be targeted. This general inhibition of signalling pathways causes often adverse effects, which could be avoided by cell type-specific inhibitors. Read More
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA; Divison of Infectious Diseases, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA. Electronic address:
Females have a higher prevalence of most autoimmune diseases; however, the mechanism is unknown. In this study, we examined the expression of tight junction protein zonula occludens 1 (ZO-1) and estrogen receptor (ER)-α/β in human primary gut tissues by immunohistochemistry, immunofluorescence and qPCR. The expression of ZO-1 and ER-β but not ER-α was present in both male and female gut tissues. Read More
Laboratory for Autoimmune Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Genome-wide association studies have identified hundreds of risk variants associated with human autoimmune diseases. Recent evidence suggests that a substantial portion of them affect gene expression in specific cell types. To obtain the functional insights of GWAS findings, comprehensive characterization of genetic variants in human genome is a key task. Read More
Institute for Inflammation Research, Center for Rheumatology and Spine Disease, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark; Haematopoietic Cell Transplantation and Primary Immune Deficiency, Department of Paediatric and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark.
Interleukin-7 is a cytokine essential for T cell homeostasis. IL-7 binds to cellular IL-7 receptors in competition with a soluble form of the receptor (sIL-7Rα). We hypothesized that altered sIL-7Rα levels may cause adverse outcomes in patients undergoing HSCT. Read More
Laboratory of Experimental Thrombosis, Institute of Experimental Medicine-CONICET, National Academy of Medicine, José Andrés Pacheco de Melo 3081, Buenos Aires, Argentina. Electronic address:
NETosis is a host defense mechanism associated with inflammation and tissue damage. Experimental models show that platelets and von Willebrand factor (VWF) are key elements for intravascular NETosis. We determined NETosis in septic and burn patients at 1 and 4days post-admission (dpa). Read More
S100A9 is an endogenous danger signal that promotes and exacerbates the neutrophilic inflammatory response. To investigate the role of S100A9 in neutrophilic asthma, S100A9 levels were measured in sputum from 101 steroid-naïve asthmatics using an ELISA kit and the levels were significantly correlated with percentages of neutrophils in sputum. Intranasal administration of recombinant S100A9 markedly increased neutrophil numbers at 8h and 24h later with concomitant elevation of IL-1β, IL-17, and IFN-γ levels. Read More
Introduction: Loss of B cell tolerance is a hallmark feature of the pathogenesis of Systemic Lupus Erythematosus (SLE). Recent advances in B cell therapy have focused on targeted therapy aimed at inhibiting B cell activation and reducing B cell survival. Belimumab, a human monoclonal antibody against B cell activating factor (BAFF) was licensed in 2011 for the treatment of SLE. Read More
Clin Immunol 2017 Aug 26;183:145-157. Epub 2017 Aug 26.
State Key Laboratory of Virology and Medical Research Institute, Hubei Province Key Laboratory of Allergy and Immunology and Department of Immunology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, PR China. Electronic address:
Ficolin-2 is an important serum complement lectin. Here, we describe novel findings indicating that serum ficolin-2 concentrations in multiple tumor patients are significantly lower than those in healthy donors. Administration of exogenous ficolin-2 or ficolin-A (a ficolin-2-like molecule in mouse), with only once, could remarkably inhibit the tumor cells growth in murine tumor models via early macrophages, dendritic cells (DCs) and CD8(+) T cells, but not CD4(+) T cells. Read More
Introduction: Macrophage activation syndrome (MAS) is a severe, hyperinflammatory life-threatening syndrome, generally complicating different rheumatic diseases. Despite the severity of the disease, little is known about the pathogenic mechanisms and, thus, possible targeted therapies in the management of these patients. Areas covered: In this review, we aimed to update the current pathogenic knowledge of MAS, during rheumatic diseases, focusing mainly on immunologic abnormalities and on new possible therapeutic strategies. Read More
Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (IEOS-CNR), Napoli, Italy; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli "Federico II", Napoli, Italy. Electronic address:
Reliable immunologic biomarkers able to monitor disease course during multiple sclerosis (MS) are still missing. We aimed at identifying possible immunometabolic biomarkers able to predict the clinical outcome in MS patients during treatment with interferon (IFN)-beta-1a. We measured in 45 relapsing-remitting (RR) MS patients, blood circulating levels of several immunometabolic markers, at enrolment, and correlated their levels to disease activity and progression over time. Read More
Clin Immunol 2017 Aug 16;183:132-141. Epub 2017 Aug 16.
Medical University of South Carolina, Division of Rheumatology and Immunology, Charleston, SC 29425, USA. Electronic address:
Systemic lupus erythematosus (SLE) is a chronic and potentially severe autoimmune disease that disproportionately affects women. Despite a known role for hormonal factors impacting autoimmunity and disease pathogenesis, the specific mechanisms of action remain poorly understood. Our laboratory previously backcrossed "estrogen receptor alpha knockout (ERαKO)" mice onto the NZM2410 lupus prone background to generate NZM/ERαKO mice. Read More
RASGRP1 is a guanine-nucleotide-exchange factor essential for MAP-kinase mediated signaling in lymphocytes. We report the second case of RASGRP1 deficiency in a patient with a homozygous nonsense mutation in the catalytic domain of the protein. The patient had epidermodysplasia verruciformis, suggesting a clinically important intrinsic T cell function defect. Read More
Clin Immunol 2017 Aug 16;183:121-131. Epub 2017 Aug 16.
Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Neurology Institute of Xiangya Hospital, Central South University, Changsha, Hunan 410008, China. Electronic address:
Abnormal CD4(+)T cell activation is known to play roles in the pathogenesis of myasthenia gravis (MG). However, little is known about the mechanisms underlying the roles of lncRNAs in regulating CD4(+) T cell. In this study, we discovered that the lncRNA IFNG-AS1 is abnormally expressed in MG patients associated with quantitative myasthenia gravis (QMG) and the positive anti-AchR Ab levels patients. Read More
Introduction: Innate lymphoid cells (ILCs) represent a diverse family of cells of the innate immune system, which play an important role in regulation of tissue homeostasis, immunity and inflammation. Emerging evidence has highlighted the importance of ILCs in both protective immunity to respiratory infections and their pathological roles in the lungs. Therefore, the aim of this review is to summarize the current knowledge, interpret and integrate it into broader perspective, enabling greater insight into the role of ILCs in respiratory diseases. Read More
The 19th annual international Targeted Therapies meeting brought together over 100 leading basic scientists and clinical researchers from around the world in the field of immunology, molecular biology and rheumatology and other specialties. During the meeting, breakout sessions were held consisting of 5 disease-specific groups with 20-40 experts assigned to each group based on clinical or scientific expertise. Specific groups included: rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, systemic lupus erythematous, connective tissue diseases (e. Read More
Introduction: Lupus Nephritis (LN) is a severe manifestation of Systemic Lupus Erythematosus (SLE) with a significant prognostic impact. Over a prolonged course, an exhaustion of treatment alternatives may occur and further therapeutic options are needed. B cells play a pivotal role in disease pathogenesis and represent an attractive therapeutic target. Read More
Introduction: Cancer immunotherapy has evolved and is aimed at generating the efficacious therapeutic modality to enhance the specificity and power of the immune system to combat tumors. Areas covered: Current efforts in cancer immunotherapy fall into three main approaches. One approach is through the blockade of immune checkpoints, another approach is through adoptive cellular therapy, and the last approach is through vaccination. Read More
B cells play a pivotal role in the initiation and perpetuation of SLE. Because SLE is molecularly and clinically heterogeneous, efficacious targeted therapy to clinical remission has not yet been established in SLE. We have found i) statistical clustering between Tfh cells and class-switched memory B cells and the upregulated transition from CXCR5(+) IgM memory B cells to CXCR3(+) class-switched memory B cells in SLE by 8-color flow cytometry, ii) the involvement of Syk, Btk and JAK in the activation and differentiation of B cells in SLE, iii) SLE patients was divided to 3 groups based on immunophenotypic analysis and statistical analysis and patients in the Tfh/class-switched B cell-dominant group were most refractory to conventional therapies although 3 groups had similar clinical features. Read More
Invariant natural killer T (iNKT) cells are cytotoxic T cells that respond to glycolipid antigens presented by CD1d. Therapeutic activation of iNKT cells with α-galactosylceramide (α-GalCer) can prevent and reverse tumor growth in mice and clinical trials involving α-GalCer-stimulated iNKT cells are ongoing in humans. B cells express CD1d, however, we show that CD1d expression is reduced on B cells from patients with chronic lymphocytic leukemia (CLL). Read More
The development of virus-like particle (VLP) technology has had an enormous impact on modern vaccinology. In order to optimize the efficacy and safety of VLP-based vaccines, adjuvants are included in most vaccine formulations. To date, most licensed VLP-based vaccines utilize the classic aluminum adjuvant compositions. Read More
X-linked severe combined immunodeficiency (X-SCID), caused by defects in the common gamma chain, is typically characterized by T and NK cell defects with the presence of B cells. T cell dysfunction and impaired class-switch recombination of B cells mean that patients typically have defects in class-switched immunoglobulins (IgG, IgA, and IgE) with detectable IgM. Here, we describe two patients with X-SCID with IgG1 gammopathy, in whom we identified maternal T and B cell engraftment. Read More
Glucocorticoids are cost-effective drugs with potent anti-inflammatory and immunosuppressive effects. They are used successfully to treat many disorders, including rheumatoid arthritis, polymyalgia rheumatic and other rheumatic diseases. However, these drugs also have the potential to cause adverse effects, particularly if high doses are used for prolonged periods. Read More
Department of Regenerative Medicine and Cell Therapy, G.R. Doshi and K.M. Mehta Institute of Kidney Diseases and Research Centre and Dr. H.L. Trivedi Institute of Transplantation Sciences (IKDRC-ITS), Civil Hospital Campus, Asarwa, Ahmedabad 380016, India.
Tolerance induction (TI) has been attempted with chimerism/clonal deletion. We report results of TI protocol (TIP) using stem cell therapy (SCT) included adipose derived mesenchymal stem cells (AD-MSC) and hematopoietic stem cells (HSC) in 10 living-donor related renal transplantation (LDRT) patients under non-myeloablative conditioning with Bortezomib, Methylprednisone, rabbit-anti-thymoglobulin and Rituximab, without using conventional immunosuppression. Transplantation was performed following acceptable lymphocyte cross-match, flow cross-match, single antigen assay and negative mixed lymphocyte reaction (MLR). Read More