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Antineoplásicos Inmunológicos , Enfermedad de Hodgkin , Antineoplásicos Inmunológicos/efectos adversos , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/tratamiento farmacológico , Humanos , Masculino , Recurrencia Local de Neoplasia/tratamiento farmacológico , Nivolumab/efectos adversosRESUMEN
Adiponectin exerts beneficial pleiotropic effects through three receptors, AdipoR1, AdipoR2, and T-cadherin; it also exerts immunomodulatory effects. We previously demonstrated that adiponectin levels are altered in common variable immunodeficiency disease (CVID). The purpose of the present study was to investigate further the specific involvement of adiponectin in CVID by characterizing (i) the expression profile of adiponectin receptors on peripheral blood mononuclear cells; (ii) the levels of another relevant adipokine, namely leptin; (iii) the levels of five other cytokines (IL-2, IL-6, IL-10, TNFα, and IFNγ) in 24 patients on maintenance therapy, in 18 treatment-naïve patients (before and 24 h after the first Ig infusion) and in 28 healthy controls. We found that (i) adiponectin was down-expressed in patients on maintenance therapy and in treatment-naïve patients, and that it increased in treatment-naïve patients 24 h after the first Ig infusion; (ii) leptin expression did not differ between maintenance patients and controls either before or after the first Ig infusion; (iii) AdipoR1 expression was significantly higher on B lymphocytes, monocytes and NK cells of CVID patients than in controls; (iv) the expression of AdipoR1 and AdipoR2 on B lymphocytes, monocytes and NK cells was higher after the first Ig infusion than in treatment-naïve patients; (v) T-cadherin expression did not differ between treatment- naïve CVID patients and controls, and was not affected by Ig infusion; and (vi) IL-6, IL-8, IL-10, and TNFα levels were differently expressed in CVID patients on therapy maintenance and were not affected by the first Ig replacement therapy. This is the first study to demonstrate that the expression of AdipoRs in peripheral blood mononuclear cells from CVID patients differs from that of controls, and changes after the first Ig infusion. The specificity of adiponectin involvement in CVID is supported by the absence of changes in leptin levels and in the levels of the cytokines investigated. Taken together, these results suggest that the adiponectin system plays an important and specific role in CVID. A better understanding of adiponectin as a link in the cross-talk between the immune system and adipose tissue may provide additional benefits for the management of CVID patients.
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Inmunodeficiencia Variable Común/tratamiento farmacológico , Citocinas/sangre , Inmunoglobulinas/administración & dosificación , Receptores de Adiponectina/inmunología , Adiponectina/sangre , Adiponectina/genética , Adulto , Cadherinas/genética , Cadherinas/inmunología , Inmunodeficiencia Variable Común/sangre , Inmunodeficiencia Variable Común/inmunología , Citocinas/inmunología , Femenino , Humanos , Inmunoglobulinas/sangre , Leptina/sangre , Leptina/genética , Leucocitos Mononucleares/inmunología , Masculino , Persona de Mediana Edad , Receptores de Adiponectina/genética , Factor de Necrosis Tumoral alfa/sangre , Adulto JovenRESUMEN
Mast cells and their mediators play a role in the control of homeostasis and in the pathogenesis of several disorders. The concept of rodent mast cell heterogeneity, initially established in the mid-1960s has been extended in humans. Human mast cells isolated and purified from different anatomic sites can be activated via aggregation of cell surface high affinity IgE receptors (FcεRI) by antigens, superantigens, anti-IgE, and anti-FcεRI. MAS-related G protein-coupled receptor-X2 (MRGPRX2) is expressed at high level in human skin mast cells (MCs) (HSMCs), synovial MCs (HSyMCs), but not in lung MCs (HLMCs). MRGPX2 can be activated by neuropeptide substance P, several opioids, cationic drugs, and 48/80. Substance P (5 × 10-7 M - 5 × 10-6 M) induced histamine and tryptase release from HSMCs and to a lesser extent from HSyMCs, but not from HLMCs and human cardiac MCs (HHMCs). Morphine (10-5 M - 3 × 10-4 M) selectively induced histamine and tryptase release from HSMCs, but not from HLMCs and HHMCs. SP and morphine were incomplete secretagogues because they did not induce the de novo synthesis of arachidonic acid metabolites from human mast cells. In the same experiments anti-IgE (3 µg/ml) induced the release of histamine and tryptase and the de novo synthesis of prostaglandin D2 (PGD2) from HLMCs, HHMCs, HSyMCs, and HSMCs. By contrast, anti-IgE induced the production of leukotriene C4 (LTC4) from HLMCs, HHMCs, HSyMCs, but not from HSMCs. These results are compatible with the heterogeneous expression and function of MRGPRX2 receptor on primary human mast cells isolated from different anatomic sites.
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Common variable immunodeficiency (CVID) is the most frequent symptomatic primary antibody deficiency in adulthood and is characterized by the marked reduction of IgG and IgA serum levels. Thanks to the successful use of polyvalent immunoglobulin replacement therapy to treat and prevent recurrent infections, non-infectious complications, including autoimmunity, polyclonal lymphoproliferation and malignancies, have progressively become the major cause of morbidity and mortality in CVID patients. The management of these complications is particularly challenging, often requiring multiple lines of immunosuppressive treatments. Over the last 5-10 years, the anti-CD20 monoclonal antibody (i.e., rituximab) has been increasingly used for the treatment of both autoimmune and non-malignant lymphoproliferative manifestations associated with CVID. This review illustrates the evidence on the use of rituximab in CVID. For this purpose, first we discuss the mechanisms proposed for the rituximab mediated B-cell depletion; then, we analyze the literature data regarding the CVID-related complications for which rituximab has been used, focusing on autoimmune cytopenias, granulomatous lymphocytic interstitial lung disease (GLILD) and non-malignant lymphoproliferative syndromes. The cumulative data suggest that in the vast majority of the studies, rituximab has proven to be an effective and relatively safe therapeutic option. However, there are currently no data on the long-term efficacy and side effects of rituximab and other second-line therapeutic options. Further randomized controlled trials are needed to optimize the management strategies of non-infectious complications of CVID.
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B cell superantigens, also called immunoglobulin superantigens, bind to the variable regions of either the heavy or light chain of immunoglobulins mirroring the lymphocyte-activating properties of classical T cell superantigens. Protein A of Staphylococcus aureus, protein L of Peptostreptococcus magnus, and gp120 of HIV are typical immunoglobulin superantigens. Mast cells are immune cells expressing the high-affinity receptor for IgE (FcεRI) and are strategically located in the human heart, where they play a role in several cardiometabolic diseases. Here, we investigated whether immunoglobulin superantigens induced the activation of human heart mast cells (HHMCs). Protein A induced the de novo synthesis of cysteinyl leukotriene C4 (LTC4) from HHMCs through the interaction with IgE VH3+ bound to FcεRI. Protein L stimulated the production of prostaglandin D2 (PGD2) from HHMCs through the interaction with κ light chains of IgE. HIV glycoprotein gp120 induced the release of preformed (histamine) and de novo synthesized mediators, such as cysteinyl leukotriene C4 (LTC4), angiogenic (VEGF-A), and lymphangiogenic (VEGF-C) factors by interacting with the VH3 region of IgE. Collectively, our data indicate that bacterial and viral immunoglobulin superantigens can interact with different regions of IgE bound to FcεRI to induce the release of proinflammatory, angiogenic, and lymphangiogenic factors from human cardiac mast cells.
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Mastocitos/inmunología , Mastocitos/metabolismo , Miocardio/inmunología , Miocardio/metabolismo , Superantígenos/inmunología , Antígenos Bacterianos/inmunología , Antígenos Virales/inmunología , Biomarcadores , Liberación de Histamina , Humanos , Inmunoglobulina E/inmunología , Inmunoglobulina G/inmunología , Inmunoglobulina M/inmunología , Infarto del Miocardio/etiología , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Miocardio/patologíaRESUMEN
Asthma is a heterogeneous disease characterized by chronic airway inflammation that results in a wide spectrum of clinical manifestations. Patients with severe asthma represent a substantial share of consumption of healthcare resources and hospitalization. Moreover, these patients are at risk of increased morbidity and mortality. Recently, several phenotypes and endotypes of asthma have been identified. The identification of specific subtypes of asthma is fundamental for optimizing the clinical benefit of novel treatments. Although in most patients the disease can be controlled by some combination of pharmacologic agents, in some 5-10% of patients the disease remains uncontrolled. Several monoclonal antibodies (mAbs) targeting pathogenetic molecules (e.g., IgE, IL-5, IL- 5Rα, IL-4, IL-13, TSLP) are currently available or under development for the treatment of different forms of severe type 2 asthma. The identification of diagnostic and predictive biomarkers (e.g., IgE, blood eosinophil count, FeNO, periostin, etc.) has revolutioned the field of targeted therapy in severe asthma. Monoclonal antibodies targeting Th2-driven inflammation are generally safe in adult patients with moderate-to-severe asthma. The long-term safety of these biologics is a relevant issue that should be addressed. Unfortunately, little is known about non-type 2 asthma. Further studies are needed to identify biomarkers to guide targeted therapies of different forms of non-type 2 asthma.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Asma/terapia , Inmunoterapia , Anticuerpos Monoclonales Humanizados/inmunología , Humanos , Interleucinas/antagonistas & inhibidores , Interleucinas/inmunologíaRESUMEN
BACKGROUND: Common variable immunodeficiency (CVID) encompasses a heterogeneous group of primary antibody deficiency disorders characterized by recurrent infections, autoimmunity and malignancies. Gastrointestinal manifestations are frequently associated with CVID. OBJECTIVE: In this cross-sectional study, we evaluated gastric and duodenal involvement in a cohort of adult patients with CVID. METHODS: Upper gastrointestinal endoscopy was performed in 58 patients (26 males, mean age 47.8±15.6 years), diagnosed with CVID according to 2014 ESID criteria. Random biopsies were collected from gastric antrum and descending duodenum for the all enrolled subjects. Intraepithelial lymphocytosis in descending duodenum was defined as the presence of 25 lymphocytes per 100 enterocytes. RESULTS: The major histopathological findings that we found were: a) chronic active gastritis (44.8%), Helicobacter pylori-associated (8.6%), b) chronic duodenitis (39.6%) with intraepithelial lymphocytosis (31%) and absence of plasma cells (18.9%) and c) autoimmune atrophic gastritis (5.2%). Three patients (5.2%) presented Intestinal Metaplasia (IM) of the gastric antrum. This finding was associated with H. pylori infection and persisted after the eradication in one patient. IM was associated with autoimmune atrophic gastritis in two cases. Giardia lamblia infection was observed in the duodenum samples from three patients (5.2%). A diagnosis of Gastric adenocarcinoma was made in a 58-year- old woman diagnosed with gastric dysplasia one year earlier. CONCLUSION: In our cohort of CVID patients, gastro-duodenal histopathological findings, including malignancies, are frequent and can affect long-term prognosis. A rigorous endoscopic follow-up is needed in CVID patients irrespective of the gastrointestinal symptoms.
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Inmunodeficiencia Variable Común/inmunología , Duodenitis/inmunología , Gastritis/inmunología , Inmunización Pasiva/métodos , Adulto , Anciano , Inmunodeficiencia Variable Común/epidemiología , Inmunodeficiencia Variable Común/patología , Inmunodeficiencia Variable Común/terapia , Estudios Transversales , Duodenitis/epidemiología , Duodenitis/patología , Endoscopía Gastrointestinal , Femenino , Gastritis/epidemiología , Gastritis/patología , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Distribución AleatoriaRESUMEN
BACKGROUND: According to the World Health Organization, air pollution is closely associated with climate change and, in particular, with global warming. In addition to melting of ice and snow, rising sea level, and flooding of coastal areas, global warming is leading to a tropicalization of temperate marine ecosystems. Moreover, the effects of air pollution on airway and lung diseases are well documented as reported by the World Allergy Organization. METHODS: Scientific literature was searched for studies investigating the effect of the interaction between air pollution and climate change on allergic and respiratory diseases. RESULTS: Since 1990s, a multitude of articles and reviews have been published on this topic, with many studies confirming that the warming of our planet is caused by the "greenhouse effect" as a result of increased emission of "greenhouse" gases. Air pollution is also closely linked to global warming: the emission of hydrocarbon combustion products leads to increased concentrations of biological allergens such as pollens, generating a mixture of these particles called particulate matter (PM). The concept is that global warming is linked to the emission of hydrocarbon combustion products, since both carbon dioxide and heat increase pollen emission into the atmosphere, and all these particles make up PM10. However, the understanding of the mechanisms by which PM affects human health is still limited. Therefore, several studies are trying to determine the causes of global warming. There is also evidence that increased concentrations of air pollutants and pollens can activate inflammatory mediators in the airways. Our Task Force has prepared a Decalogue of rules addressing public administrators, which aims to limit the amount of allergenic pollen in the air without sacrificing public green areas. CONCLUSIONS: Several studies underscore the significant risks of global warming on human health due to increasing levels of air pollution. The impact of climate change on respiratory diseases appears well documented. The last decades have seen a rise in the concentrations of pollens and pollutants in the air. This rise parallels the increase in the number of people presenting with allergic symptoms (e.g., allergic rhinitis, conjunctivitis, and asthma), who often require emergency medical care. Our hope is that scientists from different disciplines will work together with institutions, pharmaceutical companies and lay organizations to limit the adverse health effects of air pollution and global warming.
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BACKGROUND: Morbidity and mortality of primary and secondary antibody deficiencies (AD) are frequently associated with diagnostic delays. These could be avoided by a combination of factors including a widespread and effective development in screening tests. METHODS: Calculated globulin (CG), derived from the difference between serum total protein and albumin levels, reflects immunoglobulin serum levels and has shown to have a predictive value in the early diagnosis of antibody deficiencies. This study investigated the possibility to use low levels of CG to detect antibody deficiency in an Italian University Hospital. RESULTS: First, we conducted an analysis of anonymized adult samples collected at our biochemistry laboratory with a range of calculated globulin levels from 15 to 22 g/l. A CG cut-off of 19 g/l detected subjects with IgG lower than 600 mg/dl with a sensitivity of 70% and a specificity of 75%. To further verify the clinical usefulness of CG, we retrospectively evaluated the relationship between CG values and serum IgG levels in 38 patients diagnosed with CVID at our Institution. Using a CG cut-off of 19 g/l, we detected antibody deficiency in 97.3% (37/38) of the subjects present in our cohort. CONCLUSION: Finally, we chose a CG value of 19 g/l as the cut-off for a prospective AD screening program. The results of this study show that a screening CG test can be used as a tool to reduce diagnostic delays, improve long-term prognosis and reduce the healthcare costs of antibody deficiency.
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Inmunodeficiencia Variable Común/sangre , Deficiencia de IgG/sangre , Seroglobulinas/análisis , Adulto , Estudios de Cohortes , Diagnóstico Precoz , Femenino , Hospitales Universitarios , Humanos , Inmunoglobulina G/sangre , Masculino , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
Thymic stromal lymphopoietin (TSLP) is a pleiotropic cytokine originally isolated from a murine thymic stromal cell line. TSLP exerts its biological effects by binding to a high-affinity heteromeric complex composed of thymic stromal lymphopoietin receptor chain and IL-7Rα. TSLP is primarily expressed by activated lung and intestinal epithelial cells, keratinocytes, and fibroblasts. However, dendritic cells (DCs), mast cells, and presumably other immune cells can also produce TSLP. Different groups of investigators have demonstrated the existence of two variants for TSLP in human tissues: the main isoform expressed in steady state is the short form (sf TSLP), which plays a homeostatic role, whereas the long form (lfTSLP) is upregulated in inflammatory conditions. In addition, there is evidence that in pathological conditions, TSLP can be cleaved by several endogenous proteases. Several cellular targets for TSLP have been identified, including immune (DCs, ILC2, T and B cells, NKT and Treg cells, eosinophils, neutrophils, basophils, monocytes, mast cells, and macrophages) and non-immune cells (platelets and sensory neurons). TSLP has been originally implicated in a variety of allergic diseases (e.g., atopic dermatitis, bronchial asthma, eosinophilic esophagitis). Emerging evidence indicates that TSLP is also involved in chronic inflammatory (i.e., chronic obstructive pulmonary disease and celiac disease) and autoimmune (e.g., psoriasis, rheumatoid arthritis) disorders and several cancers. These emerging observations greatly widen the role of TSLP in different human diseases. Most of these studies have not used tools to analyze the expression of the two TSLP isoforms. The broad pathophysiologic profile of TSLP has motivated therapeutic targeting of this cytokine. Tezepelumab is a first-in-class human monoclonal antibody (1) that binds to TSLP inhibiting its interaction with TSLP receptor complex. Tezepelumab given as an add-on-therapy to patients with severe uncontrolled asthma has shown safety and efficacy. Several clinical trials are evaluating the safety and the efficacy of tezepelumab in different inflammatory disorders. Monoclonal antibodies used to neutralize TSLP should not interact or hamper the homeostatic effects of sf TSLP.
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Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by reduced immunoglobulin serum levels and absent or impaired antibody production. Clinical manifestations, including infections, inflammatory and autoimmune diseases, and malignancies, also involve various segments of the gastrointestinal tract. Chronic diarrhea is one of the most common gastrointestinal symptoms and may cause a wide spectrum of potentially life-threatening conditions as malabsorption and protein-energy malnutrition. We describe three female CVID adult patients presenting with chronic diarrhea, weight loss, and protein-energy malnutrition due to different underlying conditions. Our review of the literature explores the various gastrointestinal involvements in CVID and points out several histopathological findings proper of the disease, thus highlighting the relevance of the endoscopic and histological assessment in CVID patients presenting with chronic diarrhea.
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Inmunodeficiencia Variable Común/diagnóstico , Diarrea/diagnóstico , Tracto Gastrointestinal/patología , Infecciones por Helicobacter/diagnóstico , Helicobacter pylori/fisiología , Adulto , Enfermedad Crónica , Inmunodeficiencia Variable Común/complicaciones , Diarrea/complicaciones , Endoscopía , Resultado Fatal , Femenino , Infecciones por Helicobacter/complicaciones , Humanos , Persona de Mediana EdadRESUMEN
Immunoglobulin therapy is the administration of human polyvalent IgG and represents the most effective treatment to prevent recurrent infections in antibody deficiency patients. Primary antibody deficiency represents the main indication of immunoglobulin replacement therapy and includes a wide range of disorders characterized by impaired antibody production in response to pathogens and recurrent infections. However, not all primary antibody deficiency patients require immunoglobulin replacement. Indeed, immunoglobulin preparations are expensive and, once prescribed, usually result in lifelong therapy. Moreover, many patients significantly benefit from a long-term antibiotic prophylaxis and a prompt begin of antibiotic therapy in case of infectious events. Even more controversial is the decision to initiate immunoglobulin replacement therapy in secondary antibody deficiency, a heterogeneous and expanding group including B-cell lymphoproliferative syndromes, protein losing states and therapeutic agents. This review seeks to define the indication to immunoglobulin replacement in primary and secondary antibody deficiency disorders, distinguishing those in which the beginning of immunoglobulin therapy is always indicated at the same time as the diagnosis has been made, from those lacking of defined indication to replacement therapy. In addition, we propose a clinical approach, mainly based on the evaluation of infectious history, vaccine response and bronchiectasis finding, to support the decision to initiate immunoglobulin therapy in an individual patient.
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Síndrome Linfoproliferativo Autoinmune/terapia , Inmunoglobulina G/uso terapéutico , Síndromes de Inmunodeficiencia/terapia , Inmunoterapia/métodos , Vacunas/inmunología , Profilaxis Antibiótica , Bronquiectasia , Humanos , Inmunidad Heteróloga , Selección de PacienteRESUMEN
Adiponectin (Acrp30) is an adipokine widely studied for its beneficial metabolic properties. It circulates as low molecular weight (LMW), medium molecular weight (MMW), and high molecular weight (HMW) oligomers. The latter exerts the most potent biological effects. Acrp30 attracted renewed interest with the finding that it was associated with the development and progression of immune disorders. The mechanisms underlying this association and the role of Acrp30 in the pathophysiology of immune-mediated conditions remain unknown. Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by chronic activation of the immune system, impaired antibody production, and imbalanced cytokine production. In the attempt to shed light on the expression of Acrp30 in CVID, we: (a) investigated total Acrp30 and its oligomerization state in CVID patients undergoing maintenance Ig replacement therapy; (b) assessed the effects of Ig replacement therapy on Acrp30 expression in treatment-naïve CVID patients, namely, patients not treated before diagnosis, before and after the first Ig administration; and (c) evaluated the correlation between Acrp30 levels and clinical phenotypes of the disease. As controls, we analyzed healthy subjects and patients affected by a non-immunodeficiency chronic inflammatory demyelinating polyneuropathy (CIDP), before and after Ig infusion. We found that total Acrp30 and HMW oligomers were decreased in CVID but not in CIDP patients versus controls. Moreover, Acrp30 levels were correlated with IgA levels and were associated with two CVID phenotypes, namely, autoimmune cytopenia and enteropathy. Receiver operating characteristic curve analysis indicated that Acrp30 modulation is specific for CVID patients. Acrp30 and HMW levels quickly and dramatically increased after Ig infusion only in eight treatment-naïve CVID patients but not in five CIDP patients. This finding indicates that Ig administration per se is not able to induce an increase of Acrp30, but the specific cellular and/or molecular background proper of CVID seems to be essential. In conclusion, our data indicate that Acrp30 is specifically related to CVID activity. Further studies are required to understand the biological role of Acrp30 and its possible use as disease biomarker in CVID.
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Common variable immunodeficiency disorders (CVID) represent a collection of diseases leading to an absent or strongly impaired antibody production. CVID presents a wide range of immunological abnormalities and clinical manifestations, including infections, inflammatory and autoimmune diseases, and malignancies. The aim of this observational study was to analyze the epidemiological and clinical features of a cohort of 75 Italian CVID patients, and evaluate the correlation with comorbidity and mortality. Clinical data were retrospectively collected: the cohort was followed-up for a maximum of 30years (mean time of 10.24years, median of 9years). An higher age at the diagnosis of CVID and an higher age at onset of symptoms were significantly associated with a reduction of patients survival if stratified per median of IgA (less than or >8.00mg/dl). Thus IgA levels at diagnosis are correlated with patients survival contributing to identify a subset with a worse prognostic outcome.
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Inmunodeficiencia Variable Común/sangre , Inmunoglobulina A/sangre , Adulto , Anciano , Estudios de Cohortes , Inmunodeficiencia Variable Común/diagnóstico , Inmunodeficiencia Variable Común/epidemiología , Inmunodeficiencia Variable Común/inmunología , Femenino , Humanos , Italia/epidemiología , Masculino , Persona de Mediana EdadRESUMEN
Glucocorticoids and immunosuppressive drugs represent the first-line treatment of eosinophilic granulomatosis with polyangiitis (EGPA, former Churg-Strauss syndrome), even though the combined therapy is not successful in achieving the disease remission in some patients with neurological or cardiac involvement. We describe a case of an EGPA male patient with impaired left ventricular function not responsive to glucocorticoid and immunosuppressive therapy. We observed that high-dose (2g/kg/4weeks) intravenous immunoglobulin (IVIG) therapy significantly improved cardiac function, which was deteriorated after reducing IVIG dose at 0.5g/kg/4weeks, and was restored increasing again IVIG dose to 2g/kg/4weeks. The finding highlights the relevance of IVIG as treatment of choice in EGPA patients with cardiac involvement not responsive to the standard glucocorticoid and immunosuppressive therapy. Moreover, at a follow-up of 24months, the continuance of high dose IVIG therapy was required to maintain a sustained remission of the heart failure.
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Síndrome de Churg-Strauss/terapia , Granulomatosis con Poliangitis/terapia , Insuficiencia Cardíaca/terapia , Corazón/fisiología , Inmunoglobulinas Intravenosas/uso terapéutico , Inmunosupresores/uso terapéutico , Síndrome de Churg-Strauss/inmunología , Resistencia a Medicamentos , Glucocorticoides/uso terapéutico , Granulomatosis con Poliangitis/inmunología , Corazón/efectos de los fármacos , Insuficiencia Cardíaca/inmunología , Humanos , Masculino , Persona de Mediana Edad , Recuperación de la Función , Resultado del TratamientoRESUMEN
BACKGROUND: Hereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) is characterized by recurrent attacks of swelling that affect various body sites. Such attacks are a frequent cause of visits to the emergency department and are often treated in the hospital. In recent years, self-administration of C1-inhibitor (C1-INH) concentrates at home has become an increasingly used option, with a positive impact on patient outcomes and quality of life. METHODS: This was an observational study of 6 months' duration in 56 patients with C1-INH-HAE referred to a HAE center in southern Italy. The patients received three types of treatment for their swelling attacks: C1-INH concentrates administered at home (n = 25); icatibant administered at home (n = 12); and C1-INH concentrates administered in the hospital (n = 19). The objectives of this observational study were to compare therapy compliance (defined as the proportion of treated attacks) and quality of life in home- and hospital-treated patients, and to identify factors associated with the decision to use home therapy. RESULTS: Overall, 918 attacks were reported over 6 months, of which 544 (59.2 %) were treated. Total number of reported attacks and the mean (±SD) number of attacks per patient, respectively, in the three groups were: 611 and 24.4 (±26.1) for home-based C1-INH; 191 and 15.9 (±12.0) for home-based icatibant; 166 and 6.1 (±6.5) for hospital-based C1-INH. Differences in attack frequency between home- and hospital-based treatments were statistically significant (p = 0.002), while patient demographic characteristics and the disease severity score did not correlate with the use of home therapy. Compliance with therapy was significantly better with home-based therapy (71.2 % of treated attacks with C1-INH and 44.0 % with icatibant) than with hospital-based therapy (21.6 %, p = 0.003). Quality of life showed an opposite trend, with patients on hospital-based treatment reporting the highest quality of life. CONCLUSIONS: Home-based therapy was associated with better compliance compared with hospital-based therapy. The choice to adopt home-based therapy appeared to correlate with a high attack frequency. Home-based therapy is a valid treatment option for patients with C1-INH-HAE and should be offered to all such patients, and especially to those with high attack frequency.
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In this study, we compared intravenous immunoglobulins (IVIG) and subcutaneous immunoglobulins (SCIG) in terms of serum IgG concentration and incidence of infections in patients with hypogammaglobulinemia secondary to chemo-immunotherapy regimens including the anti-CD20 monoclonal antibody rituximab. Fourteen patients with a B-cell lymphoproliferative disease treated for at least six months with a rituximab-including chemo-immunotherapy regimen were recruited. Mean serum levels of IgG were higher during replacement therapy than at the end of rituximab treatment (p<0.001). Moreover, serum IgG level was higher during replacement therapy with SCIG than with IVIG (p<0.001). No differences in the incidence of infections were observed. Although the non-randomized design and the small number of patients do not allow definitive conclusions to be drawn, study results suggest that higher mean serum IgG levels are reached when using the subcutaneous route after a switch from the intravenous regimen, and that IVIG and SCIG offer comparable protection against infections.
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Agammaglobulinemia/sangre , Agammaglobulinemia/tratamiento farmacológico , Inmunoglobulina G/sangre , Inmunoglobulinas Intravenosas/uso terapéutico , Agammaglobulinemia/inducido químicamente , Anciano , Linfocitos B/efectos de los fármacos , Linfocitos B/patología , Esquema de Medicación , Femenino , Humanos , Inmunoglobulinas Intravenosas/administración & dosificación , Factores Inmunológicos/efectos adversos , Infusiones Intravenosas , Infusiones Subcutáneas , Trastornos Linfoproliferativos/sangre , Trastornos Linfoproliferativos/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Rituximab/efectos adversos , Resultado del TratamientoRESUMEN
OBJECTIVE: Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis characterized by asthma and blood eosinophilia, with the lung being the organ most frequently affected. Oral glucocorticoids and/or immunosuppressive drugs are the mainstay therapy of EGPA. Occasional reports suggest that EGPA patients can be treated with omalizumab in addition to conventional therapy to achieve asthma control. To investigate the long-term effects of omalizumab in patients with EGPA and asthma (2 females, 3 males, age 41-64 years), we carried out a 36-month follow-up observational study. At the time of enrollment, the patients were on maintenance therapy and had moderate to severe allergic asthma, eosinophilia and rhinosinusitis. Mononeuropathy/polyneuropathy and/or histological evidence of tissue eosinophilic infiltration were also present. METHODS: Patients were treated with omalizumab (300-600 mg s.c. every 2-4 weeks) as add-on therapy to prednisone, inhaled steroids and bronchodilators. During omalizumab treatment, spirometry, the asthma control test (ACT) score and eosinophilia were evaluated, and prednisone dosage was recorded. RESULTS: During the 36 months of omalizumab treatment asthma progressively improved as indicated by spirometry and the ACT score. Eosinophilia progressively decreased. The oral prednisone dose was reduced or withdrawn during treatment. No adverse events were recorded. CONCLUSIONS: In patients with EGPA and moderate to severe allergic asthma, omalizumab can be beneficial and safe. It enables corticosteroid tapering while decreasing eosinophilia and improving asthma symptoms over 36 months.