89 research outputs found
Interleukin-17 and innate immunity in infections and chronic inflammation
No full textInterleukin 17 (IL-17) includes several cytokines among which IL-17A is considered as one of the major pro-inflammatory cytokine being central to the innate and adaptive immune responses. IL-17 is produced by unconventional T cells, members of innate lymphoid cells (ILCs), mast cells, as well as typical innate immune cells, such as neutrophils and macrophages located in the epithelial barriers and characterised by a rapid response to infectious agents by recruiting neutrophils as first line of defence and inducing the production of antimicrobial peptides. Th17 responses appear pivotal in chronic and acute infections by bacteria, parasites, and fungi, as well as in autoimmune and chronic inflammatory diseases, including rheumatoid arthritis, psoriasis, and psoriatic arthritis. The data discussed in this review cumulatively indicate that innate-derived IL-17 constitutes a major element in the altered immune response against self antigens or the perpetuation of inflammation, particularly at mucosal sites. New drugs targeting the IL17 pathway include brodalumab, ixekizumab, and secukinumab and their use in psoriatic disease is expected to dramatically impact our approach to this systemic condition
Differences in biologics for treating ankylosing spondylitis: The contribution of network meta-analysis
No full textOBJECTIVE: Ankylosing Spondylitis (AS) is a chronic form of arthritis of unknown origin affecting the spine. In this study, we aimed to identify clinical and safety profiles of adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, and secukinumab that are biologic agents (biologics) mainly used for the treatment of AS, and to understand differences between them. MATERIALS AND METHODS: An extensive literature research was performed in MEDLINE and EMBASE in order to identify all network meta- analysis (NMA) and/or mixed treatment comparison (MTC) papers. NMA and/or MTC, with a ranking of the effectiveness of biologics in AS, were included in the analysis, and the adhesion to ISPOR guidelines was investigated. RESULTS: 60 studies were identified; after applying exclusion criteria methods, 7 studies underwent further analysis. Infliximab was the drug that exhibited the highest probability for achieving clinical efficacy by ASAS20 at 12 and 24 weeks. Considering only subcutaneous biologics, Golimumab achieved the highest probability for achieving the ASAS20 response at 12 weeks. CONCLUSIONS: Results from NMA on the use of biologics in AS indicates infliximab emerged as the drug with the highest probability of obtaining ASAS20 response both at 12 and 24 weeks of treatment
Personalized medicine in rheumatology : the paradigm of serum autoantibodies
No full textThe sequencing of the human genome is now well recognized as the starting point of personalized medicine. Nonetheless, everyone is unique and can develop different phenotypes of the same disease, despite identical genotypes, as well illustrated by discordant monozygotic twins. To recognize these differences, one of the easiest and most familiar examples of biomarkers capable of identifying and predicting the outcome of patients is represented by serum autoantibodies. In this review, we will describe the concept of personalized medicine and discuss the predictive, prognostic and preventive role of antinuclear antibodies (ANA), anti-citrullinated peptide antibodies (ACPA), rare autoantibodies and anti-drug antibodies (ADA), to evaluate how these can help to identify different disease immune phenotypes and to choose the best option for treating and monitoring rheumatic patients in everyday practice. The importance of ANA resides in the prediction of clinical manifestations in systemic sclerosis and systemic lupus erythematosus and their association with malignancies. ACPA have a predictive role in rheumatoid arthritis, they are associated with the development of a more aggressive disease, extra-articular manifestations and premature mortality in RA patients; moreover, they are capable of predicting therapeutic response. Rare autoantibodies are associated with different disease manifestations and also with a greater incidence of cancer. The determination of ADA levels may be useful in patients where the clinical efficacy of TNF-α inhibitor has dropped, for the assessment of a right management. The resulting scenario supports serum autoantibodies as the cornerstone of personalized medicine in autoimmune diseases
Numerical simulation of human hearing system
No full text© 2018 Isailovic et al. Hearing impairment is a problem faced by many people, mostly the elderly population but occurs even in newborns. Experimental tests performed on patients give information of the level of hearing impairment and the place where the problem is located. In order to understand process of hearing and hearing impairments it would be very useful to have a look inside, but it is not possible with any experimental equipment. However, it is possible to make a virtual look inside human auditory system by development of numerical model. Using data obtained by experimental research it is possible to make sufficiently detailed model and use it to gain new knowledge that can help in understanding of hearing process and problems with hearing. In this paper one such model will be presented. The model contains mechanical and fluid elements of the middle and inner ear
The Immune Response and the Pathogenesis of Idiopathic Inflammatory Myositis : a Critical Review
No full textThe pathogenesis of idiopathic inflammatory myositis (IIMs, including polymyositis and dermatomyositis) remains largely enigmatic, despite advances in the study of the role played by innate immunity, adaptive immunity, genetic predisposition, and environmental factors in an orchestrated response. Several factors are involved in the inflammatory state that characterizes the different forms of IIMs which share features and mechanisms but are clearly different with respect to the involved sites and characteristics of the inflammation. Cellular and non-cellular mechanisms of both the immune and non-immune systems have been identified as key regulators of inflammation in polymyositis/dermatomyositis, particularly at different stages of disease, leading to the fibrotic state that characterizes the end stage. Among these, a special role is played by an interferon signature and complement cascade with different mechanisms in polymyositis and dermatomyositis; these differences can be identified also histologically in muscle biopsies. Numerous cellular components of the adaptive and innate immune response are present in the site of tissue inflammation, and the complexity of idiopathic inflammatory myositis is further supported by the involvement of non-immune mechanisms such as hypoxia and autophagy. The aim of this comprehensive review is to describe the major pathogenic mechanisms involved in the onset of idiopathic inflammatory myositis and to report on the major working hypothesis with therapeutic implications
Clinical Trials Supporting the Role of the IL-17/IL-23 Axis in Axial Spondyloarthritis
No full textThe term spondyloarthritis (SpA) encompasses a heterogeneous group of inflammatory musculoskeletal diseases with several common genetic background and clinical features, including the possible involvement of the axial skeleton with peripheral mono- or oligo- arthritis and frequently coexisting skin, eye and intestinal manifestations. When the sacroiliac joints or other parts of the spine or thoracic wall are predominantly affected at magnetic resonance or X-ray imaging with inflammatory back pain, the disease is classified as axial SpA and the therapeutic choices are significantly different compared to cases of peripheral arthritis. Moving from the narrow effectiveness and safety profiles of non-steroidal anti-inflammatory drugs, there has been a significant research effort aimed at identifying new treatments based on our better understanding of the pathogenesis of SpA. Indeed, in parallel with the solid data demonstrating that IL-17 and IL-23 are key cytokines in the development of enthesitis and spondylitis, monoclonal antibodies interfering with this pathway have been developed for the treatment of axial SpA. Furthermore, the IL-17/IL-23 axis is key to extra-articular manifestations such as inflammatory bowel disease, uveitis, and psoriasis which are frequent comorbidities of SpA. Currently available drugs act through these mechanisms recognizing IL-23 and targeting IL-17, such as secukinumab and ixekizumab. These therapeutic approaches are now envisioned in the international treatment recommendations for psoriatic arthritis with an axial phenotype as well as for ankylosing spondylitis (AS). We will provide herein a concise comprehensive overview of the clinical evidence supporting the use of these and other drugs acting on IL-23 and IL-17 in axial SpA
Detection of anti-mitochondrial antibodies by immunoprecipitation in patients with systemic sclerosis
No full textObjective To describe a new immunoprecipitation pattern identified in Italian patients affected by systemic sclerosis (SSc), corresponding to the pyruvate dehydrogenase antigen complex recognized by anti-mitochondrial antibodies (AMA) in primary biliary cholangitis (PBC). Methods Autoantibodies in sera from 85 patients with SSc were tested by protein- and RNA-immunoprecipitation. Immunoprecipitation-Western blot was used to determine the identified proteins, and medical records re-evaluated for liver function tests and PBC. Results In 13/85 (15%) SSc sera, a unique set of 75-50-40-34 kD proteins that had not been previously reported, was noted. The four proteins were identified as the proteins X/E3BP, E1α E1Î2 and E2/E3 of the pyruvate dehydrogenase antigen complex by immunoprecipitation-Western blot. From clinical record evaluation, 9/13 (69%) SSc patients with this new pattern were positive for AMA by routine indirect immunofluorescence, and 7/13 (54%) had a diagnosis of PBC, while 4/13 (31%) manifested no biochemical signs of cholestasis. Twelve of 13 patients with SSc and AMA by immunoprecipitation have a limited cutaneous form of SSc and anti-centromere antibodies. Conclusions We describe a pattern of 4 proteins in 15% of SSc patients, identified for the first time by protein-immunoprecipitation. This pattern corresponds to serum AMA against the pyruvate dehydrogenase antigen complex and it must be considered in the interpretation of protein-immunoprecipitation results
FRI0130 Certolizumab pegol exposure during pregnancy in women with rheumatoid arthritis: evaluation of the long-term newborn outcomes
No full textNumerical simulation of human hearing system
No full textHearing impairment is a problem faced by many people, mostly the elderly population but occurs even in newborns. Experimental tests performed on patients give information of the level of hearing impairment and the place where the problem is located. In order to understand process of hearing and hearing impairments it would be very useful to have a look inside, but it is not possible with any experimental equipment. However, it is possible to make a virtual look inside human auditory system by development of numerical model. Using data obtained by experimental research it is possible to make sufficiently detailed model and use it to gain new knowledge that can help in understanding of hearing process and problems with hearing. In this paper one such model will be presented. The model contains mechanical and fluid elements of the middle and inner ear. © 2018 Isailovic et al
Effects of type II collagen epitope carbamylation and citrullination in HLA-DR4+ monozygotic twins discordant for rheumatoid arthritis
No full textThe aim of the study is to investigate the effect of the native, citrullinated or carbamylated type II-human collagen T cell- and B cell-epitopes on the adaptive immune response in rheumatoid arthritis (RA). Peripheral blood T and B cells obtained from an HLA-DR4+ woman with early RA, her healthy monozygotic twin, and an unrelated HLA-DR3+ woman with early RA were analyzed for activation (CD154/CD69), apoptosis (annexin/7-AAD), cytokine production (INFγ/IL-17/IL-4/IL-10/IL-6), and functional phenotype (CD45Ra/CCR7) after stimulation with the collagen native T cell-epitope (T261-273), the K264 carbamylated T cell-epitope (carT261-273), the native B cell-epitope (B359-369), or the R360 citrullinated B cell-epitope (citB359-369), and the combinations of these. The T cell memory compartment was activated by T cell-epitopes in both discordant DR4+ twins, but not in the DR3+ RA. The collagen-specific activation of CD4+ T cells was induced with both the native and carbamylated T cell-epitopes only in the RA twin. Both T cell-epitopes also induced IL-17 production in the RA twin, but a greater IL-4 and IL-10 response in the healthy twin. The citrullinated B cell-epitope, particularly when combined with the carbamylated T cell-epitope, induced B cell activation and an increased IL-6/IL-10 ratio in the RA twin compared to a greater IL-10 production in the healthy twin. Our data suggest that circulating collagen-specific T and B cells are found in HLA-DR4+ subjects, but only in RA activated cells express costimulatory molecules and produce pro-inflammatory cytokines. Carbamylation and citrullination further modulate the activation and cytokine polarization of T and B cells. This article is protected by copyright. All rights reserved
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