Deplezione B linfocitaria e sindrome di Sjögren primaria: esiste un ruolo per il rituximab? = B-cell depletion and primary Sjögren’s syndrome: is there a role for rituximab?

L\u2019idea che la deplezione dei B linfociti potesse essere utilizzata per il trattamento delle malattie reumatiche sistemiche deriva dall\u2019ipotesi che, eliminando le cellule alterate dal circolo, si possa curare la malattia. In realt\ue0, nelle malattie reumatiche sistemiche, contrariamente a quanto accade nei linfomi, la deplezione dei B linfociti persiste per alcuni mesi e successivamente si assiste alla riacutizzazione della malattia. Molteplici sono le ipotesi che possono spiegare tale evento: a) insufficiente deplezione dei cloni patogeni; b) persistenza di anticorpi patogeni; c) alterazione primaria o secondaria della tolleranza dei B linfociti; d) ricomparsa delle B cellule; e) reminiscenza della malattie da parte di cellule diverse dai B linfociti, probabilmente T linfociti (1, 2)..

Neurophysiological background for physical therapies in fibromyalgia

This paper describes the techniques for controlling pain by the physical means that are most widely used clinically, particularly in the case of fibromyalgia. They are grouped on the basis of the physical energy used: mechanical, thermal (including magnetic and electromagnetic), and light (LASER). The main underlying neu-rophysiological mechanisms are gate activation, the stimulation of descending systems of pain control, and the endogenous opiate system

Microbial Agents as Putative Inducers of B Cell Lymphoma in Sjögren's Syndrome through an Impaired Epigenetic Control : The State-of-The-Art

Introduction: Understanding the mechanisms underlying the pathogenesis of Sj\uf6gren's syndrome (SS) is crucially important in order to be able to discriminate the steps that lead to B cell transformation and promptly identify the patients at risk of lymphomagenesis. The aim of this narrative review is to describe the evidence concerning the role that infections or dysbiosis plays in the epigenetic control of gene expression in SS patients and their possible involvement in B cell lymphomagenesis. Materials and Methods: We searched the PubMed and Google Scholar databases and selected a total of 92 articles published during the last 25 years that describe experimental and clinical studies of the potential associations of microbiota and epigenetic aberrations with the risk of B cell lymphoma in SS patients. Results and Discussion: The genetic background of SS patients is characterized by the hyperexpression of genes that are mainly involved in regulating the innate and adaptive immune responses and oncogenesis. In addition, salivary gland epithelial cells and lymphocytes both have an altered epigenetic background that enhances the activation of proinflammatory and survival pathways. Dysbiosis or chronic latent infections may tune the immune response and modify the cell epigenetic machinery in such a way as to give B lymphocytes an activated or transformed phenotype. It is also worth noting that transposable integrated retroelements may participate in the pathogenesis of SS and B cell lymphomagenesis by inducing DNA breaks, modulating cell gene expression, or generating aberrant transcripts that chronically stimulate the immune system. Conclusions: Microorganisms may epigenetically modify target cells and induce their transcriptome to generate an activated or transformed phenotype. The occurrence of lymphoma in more than 15% of SS patients may be the end result of a combination of genetics, epigenetics, and dysbiosis or latent infections

Determinants of Risk Infection During Therapy with Anti TNF-Alpha Blocking Agents in Rheumatoid Arthritis

The use of TNF-alpha antagonists (infliximab, etanercept, adalimumab) has changed the course of many rheumatic diseases including rheumatoid arthritis (RA). Since their approval, some questions regarding their safety including infections have been observed. The aim of the study was to evaluate the changes in cytokines levels and cells subsets in patients with RA during anti TNF blocking agents treatment and the possible effect on infections’ development. We evaluated in 89 RA patients [39 treated with etanercept (ETN), 29 with adalimumab (ADA) and 21 with infliximab (IFN)] at baseline and after 6 months the following parameters: procalcitonin, ESR, CRP, cytokines as TNF, IL-6, IL-10, IL-8 and the TNF/IL-10 ratio, and peripheral mononuclear cells as CD3+, CD3+/CD4+, CD3+/CD8+, CD19+, CD3- /CD16+/56+, CD14+HLADR+, CD20+, CD19+/CD38+. Peripheral mononuclear cells were detected by flow cytometric system Cytomics FC500 and cytokines circulating levels by a quantitative sandwich enzyme immunoassay technique (Human IL-8 Instant ELISAe Bioscience, Human IL-6 Instant ELISA e Bioscience, Human IL-10 Instant ELISAe Bioscience and Human TNF-a Quantikine immunoassay RD system). A lower reduction of CD14+HLADR+ in ADA group 54.6±10.4% vs ETA 48.4±15.7% vs INF 40.7±16.5%, p<0.039 was found. No differences in all three groups on peripheral mononuclear cells CD3+, CD3+/CD4+, CD3+/CD8+, CD19+, CD 20+, CD19+/CD38+, CD3-/CD16+/56+, and cytokine circulating levels were found. The number of infections at 6 months was: 10.3% in ADA group, 12.8% in ETN group and 19.04% in IFN group. A correlation was found between the reduction in CD14+HLADR+ cells and IFN treatment. Our data showed that the level of CD14+HLADR+ cells was reduced during therapy with IFN. ADA and ETN don’t reduce lymphocyte populations and their subsets such as CD14+HLADR+ cells that play an important role host defence

Psychiatric problems in fibromyalgia : clinical and neurobiological links between mood disorders and fibromyalgia

Objective. To review the literature addressing the relationship between mood disorders and fibromyalgia/chron-ic pain and our current understanding of overlapping pathophysiological processes and pain and depression circuitry. Methods. We selectively reviewed articles on the co-occurrence of mood disorders and fibromyalgia/chronic pain published between 1990 and July 2012 in PubMed. Bibliographies and cross references were considered and included when appropriate. Results. Forty-nine out of 138 publications were retained for review. The vast majority of the studies found an association between depression and fibromyalgia. There is evidence that depression is often accompanied by symptoms of opposite polarity characterised by heights of mood, thinking and behaviour that have a considerable impact on pharmacological treatment. Recent developments support the view that the high rates of fibromyalgia and mood disorder comorbidity is generated by largely overlapping pathophysiological processes in the brain, that provide a neurobiological basis for the bidirectional, mutually exacerbating and disabling relationship between pain and depression. Conclusions. The finding of comparable pathophysiological characteristics of pain and depression provides a framework for understanding the relationship between the two conditions and sheds some light on neurobio-logical and therapeutic aspects

Safety of rituximab in rheumatoid arthritis

La artrite reumatoide \ue8 una malattia cronica che predispone alla comparsa di complicanze rappresentate da malattie infettive, neoplasie e malattie cardiovascolari. Il rischio \ue8 aumentato dalla necessit\ue0 di assumere a lungo farmaci immunomodultori, quali ad esempio i farmaci biotecnologici. La sicurezza del rituximab \ue8 stata valutata in un periodo di tempo medio (non superiore ai 10 anni) e i dati disponibili sono rassicuranti. Nei trials clinici condotti sia in pazienti gi\ue0 trattati (con antagonisti del TNF e/o con methotrexate) sia in pazienti naive \ue8 emerso che il rituximab \ue8 tollerato anche dopo diversi cicli di terapia. La percentuale totale di eventi avversi \ue8 infatti rimasta stabile nei vari cicli. L\u2019evento avverso pi\uf9 frequente era rappresentato dalla comparsa di reazioni infusionali. La percentuale di infezioni serie non aumentava dopo diversi cicli. I dati ottenuti da esperienze condotte nella vita quotidiana confermano il buon profilo di tollerabilit\ue0.Rheumatoid arthritis (RA) is a chronic disease that requires long-term administration of immunomodulatory drugs with a greater risk of side effects like malignancies, serious infections and cardiovascular diseases. Furthermore, patients with RA are more prone than the general population to these manifestations. Safety of rituximab has been evaluated in the short-term (6 months) and in the medium-term (up to 10 years) in patients who had been previously treated with antagonists of tumor necrosis factor (a-TNF) and/or with methotrexate (MTX) and in patients who were not. Data obtained from clinical trials demonstrated that rituximab is well tolerated either after a single course or after multiple courses. The overall rate of adverse events (AEs) was stable after the first three courses. The most frequent adverse event was infusion-related reactions (IRR). Serious infections did not increase after multiple courses. Data from "real life" confirm that treatment with rituximab is well tolerated