Immunoallergology Unit

IT Florence, Italy

Immunoallergology Unit

IT Florence, Italy

Time filter

Source Type

Cantini F.,Hospital of Prato | Nannini C.,Hospital of Prato | Niccoli L.,Hospital of Prato | Iannone F.,University of Bari | And 6 more authors.
Autoimmunity Reviews | Year: 2015

Since the introduction of biologics for the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and psoriasis (Pso) an increased risk of tuberculosis (TB) reactivation in patients with latent tuberculosis infection (LTBI) has been recorded for anti-TNF agents, while a low or absent risk is associated with the non-anti-TNF targeted biologics. To reduce this risk several recommendation sets have been published over time, but in most of them the host-related risk, and the predisposing role to TB reactivation exerted by corticosteroids and by the traditional disease-modifying anti-rheumatic drugs has not been adequately addressed. Moreover, the management of the underlying disease, and the timing of biologic restarting in patients with TB occurrence have been rarely indicated. A multidisciplinary expert panel, the Italian multidisciplinary task force for screening of tuberculosis before and during biologic therapy (SAFEBIO), was constituted, and through a review of the literature, an evidence-based guidance for LTBI detection, identification of the individualized level of risk of TB reactivation, and practical management of patients with TB occurrence was formulated. The literature review confirmed a higher TB risk associated with monoclonal anti-TNF agents, a low risk for soluble receptor etanercept, and a low or absent risk for non-anti-TNF targeted biologics. Considering the TB reactivation risk associated with host demographic and clinical features, and previous or current non-biologic therapies, a low, intermediate, or high TB reactivation risk in the single patient was identified, thus driving the safest biologic choice. Moreover, based on the underlying disease activity measurement and the different TB risk associated with non-biologic and biologic therapies, practical indications for the treatment of RA, PsA, AS, and Pso in patients with TB occurrence, as well as the safest timing of biologic restarting, were provided. © 2015 Elsevier B.V.


Matucci A.,Immunoallergology Unit | Vultaggio A.,Immunoallergology Unit
Journal of Rheumatology | Year: 2014

In this review, recent insights into innate and adaptive cellular and humoral immune response to Mycobacterium tuberculosis (Mtb) are discussed and the role of specific cytokines such as tumor necrosis factor-α (TNF-α) is highlighted. According to recent findings, the immune system plays a key role in avoiding mycobacteria dissemination. The importance of different cell types (macrophages, dendritic cells, interferon-g-producing T cells) as well as the production of proinflammatory cytokines such as interleukin 6 (IL-6), IL-12, and IL-23/IL-17 have been demonstrated. Alveolar macrophages are considered the first cells infected by Mtb during respiratory infection. Mtb proliferates within alveolar macrophages and dendritic cells and induces the release of cytokines such as TNF-α, IL-1, IL-6, and IL-12. Toll-like receptors-stimulated dendritic cells link innate and adaptive immunity by promoting polarization of effector T cells. The efficient induction of Th1 immunity is decisive in defense against Mtb. In fact, host effector immune response against Mtb is related to the presence of a Th1 response. The definition of the cellular and molecular mechanisms involved in the immune response to Mtb can be helpful in developing new preventive strategies to avoid infection relapse, particularly in patients treated with biological agents. © 2014. All rights reserved.


PubMed | University Utrecht, Helmholtz Center Munich, Complutense University of Madrid, University of Lausanne and 10 more.
Type: Journal Article | Journal: Allergy | Year: 2015

Biologic agents (also termed biologicals or biologics) are therapeutics that are synthesized by living organisms and directed against a specific determinant, for example, a cytokine or receptor. In inflammatory and autoimmune diseases, biologicals have revolutionized the treatment of several immune-mediated disorders. Biologicals have also been tested in allergic disorders. These include agents targeting IgE; T helper 2 (Th2)-type and Th2-promoting cytokines, including interleukin-4 (IL-4), IL-5, IL-9, IL-13, IL-31, and thymic stromal lymphopoietin (TSLP); pro-inflammatory cytokines, such as IL-1, IL-12, IL-17A, IL-17F, IL-23, and tumor necrosis factor (TNF); chemokine receptor CCR4; and lymphocyte surface and adhesion molecules, including CD2, CD11a, CD20, CD25, CD52, and OX40 ligand. In this task force paper of the Interest Group on Biologicals of the European Academy of Allergy and Clinical Immunology, we review biologicals that are currently available or tested for the use in various allergic and urticarial pathologies, by providing an overview on their state of development, area of use, adverse events, and future research directions.


Maggi E.,University of Florence | Vultaggio A.,Immunoallergology Unit | Matucci A.,Immunoallergology Unit
Expert Review of Clinical Immunology | Year: 2011

This article reports recent evidence on epidemiological data concerning monoclonal antibody (mAb) infusion-related anaphylaxis, as well as recent data on the correlation between mAb immunogenicity and safety profiles. Pathogenic mechanisms of mAb-related adverse reactions including hypersensitivity, IgE- and non-IgE-mediated events and cytokine release syndrome are also highlighted. Finally, the role of serum anti-mAb antibodies as markers to monitor the safety of such therapeutical compounds are extensively evaluated. The anaphylaxis occurring during therapy with the anti-TNF-α mAb infliximab, largely used in immune-mediated diseases, has been taken as a paradig. © 2011 Expert Reviews Ltd.


Vultaggio A.,Immunoallergology Unit | Matucci A.,Immunoallergology Unit | Nencini F.,University of Florence | Pratesi S.,University of Florence | And 5 more authors.
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2010

Background: Infliximab is a chimeric monoclonal antibody against TNF-α useful in the treatment of many chronic inflammatory diseases. Severe anaphylaxis has been reported during therapy, although the exact mechanism has not been fully defined. The reactions have been related to the infliximab immunogenicity and development of specific antibodies. Aims of the study: Evaluation of the development of IgE and non-IgE antibodies to infliximab and their relationship with infusion reaction. Methods: Seventy-one patients (11 reactives, 11 therapeutically nonresponders, and 49 unreactive therapeutically responders) and 20 non-infliximab-exposed control subjects (ten rheumatoid arthritis, five spondyloarthropathies, five vasculitis) were evaluated for the presence of IgE (ImmunoCAP assay), IgM, and non-isotype-specific (ELISA assays) anti-infliximab antibodies. Sera were obtained at baseline and during the course of treatment, before each infliximab infusion. Results: Eleven out of 71 patients had a hypersensitivity reaction to infliximab. Non-isotype-specific anti-infliximab antibodies were detected in eight reactive and two nonresponder patients. Three patients with severe reactions displayed anti-infliximab IgE antibodies and positive skin testing. Detectable levels of anti-infliximab IgM antibodies were shown in three additional IgE- and skin testing-negative patients. IgE and IgM antibodies to infliximab were not detectable in the two nonresponder patients. Antibodies developed before the 2nd and the 3rd infusion, and their appearance was strictly related to the timing of the reaction. Conclusions: This report indicates that in some patients with infliximab-related severe reactions, IgE or IgM antibodies against infliximab were detectable. The majority of reactions could be predicted by the appearance of anti-infliximab antibodies. © 2009 John Wiley & Sons A/S.


Vultaggio A.,Immunoallergology Unit | Matucci A.,Immunoallergology Unit | Nencini F.,University of Florence | Pratesi S.,University of Florence | And 7 more authors.
International Archives of Allergy and Immunology | Year: 2012

Rituximab (RTX) is currently used in the treatment of lymphoproliferative diseases and of several rheumatologic disorders and is a frequent cause of acute infusion reactions, usually classified as cytokine release syndrome (CRS). Some infusion reactions to RTX raise concern for immediate type I hypersensitivity, even if to date RTX-specific IgE antibodies have not been reported. To improve knowledge of the mechanisms of reactions to RTX, we investigated humoral and cellular immune responses to this drug in a patient suffering from rheumatoid arthritis who displayed two immediate infusion-related reactions. RTX-exposed tolerant patients and healthy untreated subjects were used as controls. Non-isotype-specific and IgE anti-RTX antibodies were positive in the serum samples collected from the reactive patient but not in those from the control groups. Only the reactive patient also displayed skin testing positivity with RTX. More importantly, RTX-stimulated peripheral blood mononuclear cells from the reactive patient, but not from the controls, displayed a dose-dependent proliferative response associated with a Th2 cytokine production profile. Our results show the presence of RTX-specific Th2-type cells and IgE antibodies, thus suggesting that type I hypersensitivity may be an additional mechanism to CRS in the development of RTX reactions. Copyright © 2012 S. Karger AG, Basel.


Matucci A.,Immunoallergology Unit | Pratesi S.,University of Florence | Petroni G.,University of Florence | Nencini F.,University of Florence | And 4 more authors.
Clinical and Experimental Allergy | Year: 2013

Background: The administration of biological agents is potentially affected by IgE-mediated infusion reactions. Objective: The aim of the study was to evaluate the utility of skin testing in patients who have experienced infliximab (IFX)-related reactions. Methods: Thirty patients with previous immediate hypersensitivity reaction to IFX, 20 disease-matched non exposed subjects, 15 IFX-treated disease-matched tolerant patients and 15 IFX non-responder patients were enrolled. Non-isotype-specific and IgE anti-drug antibodies (ADAs) were measured by a double-capture ELISA kit and ImmunoCAP assay, respectively. Prick and intra-dermal tests were carried out with the commercial IFX preparation serially diluted. Results: Skin testing, performed in 23 of 30 reactive patients, resulted positive in 7 of them (30.4%), whereas no positivity was found in other groups of patients. The majority of reactive patients displayed non-isotype-specific ADAs (23/30, 76.6%) and the presence of anti-IFX IgE antibodies was detected in 6 of them (26%). All 6 IgE-positive reactive patients showed skin testing positivity. One reactive ADAs-positive patient who resulted skin test positive, with no detectable serum IFX-specific IgE ADAs, was also found. Skin testing positivity was associated with severe and early reactions (within the 3rd dose). No unexpected adverse reactions to skin testing were recorded. Conclusions and Clinical Relevance: This study shows that about 30% of reactive patients display skin testing positivity. They usually develop severe reactions, mainly during the first administrations of IFX. The specificity and the safety of skin testing procedure for this biological agent are also confirmed. © 2013 John Wiley & Sons Ltd.


Nencini F.,University of Florence | Pratesi S.,University of Florence | Petroni G.,University of Florence | Matucci A.,Immunoallergology Unit | And 2 more authors.
Drug Development Research | Year: 2014

Enabling Technology, Genomics, Proteomics Preclinical Development Toxicology, Formulation Drug Delivery, Pharmacokinetics Some patients with chronic inflammatory diseases either do not respond to or lose their initial responsiveness to Tumor Necrosis Factor (TNF) inhibitor therapy. In these patients, the clinical response after switching to another anti-TNF drug suggests that lack of response is not related to the therapeutic target itself but immunogenicity. All biologics are potentially immunogenic and can induce the development of antidrug antibodies (ADAs). ADA formation is associated with lower serum drug levels, infusion reactions, and loss of response. Analytical methods for ADA detection include enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA), surface plasmon resonance, and electrochemiluminescence. Currently, RIA and ELISA are the preferred methods due to a combination of reproducibility, sensitivity, and cost but have some limitations. There is no single available assay that has all pros and no cons, and therefore the use of more methods for the assessment of samples is a high priority. © 2014 Wiley Periodicals, Inc.


PubMed | University of Padua, University of Bari, University of Foggia, University of Rome Tor Vergata and 3 more.
Type: | Journal: Pulmonary pharmacology & therapeutics | Year: 2015

Few data are available on the proportion of asthmatics achieving a good asthma control (according GINA guidelines) and on the level of airway inflammation during omalizumab treatment. The aim of this cross-sectional national observational study was to assess the level of control (according to GINA guidelines) achieved in a group of asthmatics on omalizumab treatment, and to characterize the factors that influence the lack of control. We studied 306 asthmatics under omalizumab treatment for a median of 32 months (range 4-120). The level of control according to GINA was good in 25.2%, partial in 47.1% and poor in 24.5% of patients (data were missing for the remaining 3.2%). Comparison between poorly controlled and partially or well controlled asthmatics showed a statistically significant higher prevalence of some comorbidities in the first group, namely obesity, gastro-oesophageal reflux disease (GORD), aspirin intolerance and mental disorders (all p<0.001). Similarly, asthmatics with at least one exacerbation in the last year showed a significantly higher prevalence of obesity, chronic rhinosinusitis, nasal polyps, GORD, and aspirin intolerance (all p<0.05) than patients without exacerbations. When we selected patients without relevant comorbidities (upper airways disease, GORD, obesity, aspirin intolerance) and not currently smoking (N=73), the percentage of well or partially controlled asthmatics was significantly higher than in patients with comorbidities (84.9% vs 71.1%, p=0.02); the rate of asthmatics without exacerbations in the last year was also higher (73.6% vs 51.1%, p=0.001). During omalizumab treatment, a high percentage of asthmatics obtain a good or partial control of asthma. Comorbidities are associated with the lack of asthma control and persistence of exacerbations.


PubMed | Immunoallergology Unit, University of Florence and Gastroenterology Unit
Type: Journal Article | Journal: Clinical and experimental immunology | Year: 2016

Antibodies recognizing infliximab (IFX) may develop in a proportion of treated patients, leading to loss of response or hypersensitivity reactions (HRs). T cell response to IFX has been poorly investigated. This paper was addressed to detect IFX-specific T cells in treated patients with inflammatory diseases developing, or not, anti-drug antibodies (ADA) and to correlate the presence of specific T cells with the clinical outcomes of the treatment. A co-culture system of IFX-loaded dendritic cells and purified autologous CD4

Loading Immunoallergology Unit collaborators
Loading Immunoallergology Unit collaborators