Publications by authors named "Ilaria Mormile"

13 Publications

  • Page 1 of 1

Common Variable Immunodeficiency and Autoimmune Diseases: A Retrospective Study of 95 Adult Patients in a Single Tertiary Care Center.

Front Immunol 2021 5;12:652487. Epub 2021 Jul 5.

Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy.

Common variable immunodeficiency (CVID) is the most common clinically significant primary immunodeficiency in adulthood, which presents a broad spectrum of clinical manifestations, often including non-infectious complications in addition to heightened susceptibility to infections. These protean manifestations may significantly complicate the differential diagnosis resulting in diagnostic delay and under-treatment with increased mortality and morbidity. Autoimmunity occurs in up to 30% of CVID patients, and it is an emerging cause of morbidity and mortality in this type of patients. 95 patients (42 males and 53 females) diagnosed with CVID, basing on ESID diagnostic criteria, were enrolled in this retrospective cohort study. Clinical phenotypes were established according to Chapel 2012: i) no other disease-related complications, ii) cytopenias (thrombocytopenia/autoimmune hemolytic anemia/neutropenia), iii) polyclonal lymphoproliferation (granuloma/lymphoid interstitial pneumonitis/persistent unexplained lymphadenopathy), and iv) unexplained persistent enteropathy. Clinical items in the analysis were age, gender, and clinical features. Laboratory data included immunoglobulin (Ig)G, IgM and IgA levels at diagnosis, flow-cytometric analysis of peripheral lymphocytes (CD3+, CD3+CD4+, CD3+CD8+, CD19+, CD4+CD25highCD127low, CD19hiCD21loCD38lo, and follicular T helper cell counts). Comparisons of continuous variables between groups were performed with unpaired t-test, when applicable. 39 patients (41%) showed autoimmune complications. Among them, there were 21 females (53.8%) and 18 males (46.2%). The most prevalent autoimmune manifestations were cytopenias (17.8%), followed by arthritis (11.5%), psoriasis (9.4%), and vitiligo (6.3%). The most common cytopenia was immune thrombocytopenia, reported in 10 out of 95 patients (10.5%), followed by autoimmune hemolytic anemia (n=3, 3.1%) and autoimmune neutropenia (n=3, 3.1%). Other autoimmune complications included thyroiditis, coeliac disease, erythema nodosum, Raynaud's phenomenon, alopecia, recurring oral ulcers, autoimmune gastritis, and primary biliary cholangitis. There were no statistically significant differences comparing immunoglobulin levels between CVID patients with or without autoimmune manifestations. There was no statistical difference in CD3+, CD8+, CD4+CD25highCD127low T, CD19, CD19hiCD21loCD38lo, and follicular T helper cell counts in CVID patients with or without autoimmune disorders. In conclusion, autoimmune manifestations often affect patients with CVID. Early recognition and tailored treatment of these conditions are pivotal to ensure a better quality of life and the reduction of CVID associated complications.
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http://dx.doi.org/10.3389/fimmu.2021.652487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287325PMC
July 2021

The N-Formyl Peptide Receptors and Rheumatoid Arthritis: A Dangerous Liaison or Confusing Relationship?

Front Immunol 2021 18;12:685214. Epub 2021 Jun 18.

Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by a progressive symmetric inflammation of the joints resulting in bone erosion and cartilage destruction with a progressive loss of function and joint deformity. An increased number of findings support the role of innate immunity in RA: many innate immune mechanisms are responsible for producing several cytokines and chemokines involved in RA pathogenesis, such as Tumor Necrosis Factor (TNF)-α, interleukin (IL)-6, and IL-1. Pattern recognition receptors (PRRs) play a crucial role in modulating the activity of the innate arm of the immune response. We focused our attention over the years on the expression and functions of a specific class of PRR, namely formyl peptide receptors (FPRs), which exert a key function in both sustaining and resolving the inflammatory response, depending on the context and/or the agonist. We performed a broad review of the data available in the literature on the role of FPRs and their ligands in RA. Furthermore, we queried a publicly available database collecting data from 90 RA patients with different clinic features to evaluate the possible association between FPRs and clinic-pathologic parameters of RA patients.
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http://dx.doi.org/10.3389/fimmu.2021.685214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253054PMC
June 2021

Clinical predictors of psoriatic arthritis and osteoclast differentiation.

Exp Dermatol 2021 Jun 30. Epub 2021 Jun 30.

Department of Advanced Biomedical Sciences University of Naples Federico II, Naples, Italy.

Psoriasis and psoriatic arthritis (PsA) are interrelated inflammatory diseases. Psoriasis usually precedes PsA onset and represents a well-established risk factor for PsA development. Bone erosion is a hallmark of PsA, and the contribution of cutaneous psoriatic inflammation in this process has been demonstrated. However, little is still known on the pathogenetic mechanisms that link psoriatic skin to joint damage. Clinical features of psoriatic disease, including specific body site involvement, seem to be important risk predictors of PsA. The aim of this pilot research study was to investigate if psoriatic cutaneous inflammation, affecting these anatomical predictive sites for PsA, could be linked to osteoclast differentiation and activity. Our results showed that psoriasis skin localizations were positively related to the osteoclastogenic profile in psoriatic patients. These results provide new insights into the fascinating skin-joint axis concept.
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http://dx.doi.org/10.1111/exd.14424DOI Listing
June 2021

Real-life evidence of low-dose mepolizumab efficacy in EGPA: a case series.

Respir Res 2021 Jun 23;22(1):185. Epub 2021 Jun 23.

Department of Translational Medical Sciences, University of Naples Ferderico II, Naples, Italy.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare, small vessel, necrotizing vasculitis. The disease is mainly characterized by hypereosinophilia and asthma with frequent sinonasal involvement, although multiple organs can be affected, including the heart, lungs, skin, gastrointestinal tract, kidneys, and nervous system. IL-5 production is pathogenetically central for the development of the disease by promoting proliferation, transvascular migration and functional activation of eosinophils. The degree of blood and tissue eosinophilia appears to be associated with disease pathogenesis and eosinophil depletion represents a promising treatment approach for EGPA. We prospectively evaluated the efficacy and safety of a low dose (100 mg q4w), 12-month course of mepolizumab, an anti-IL-5 monoclonal antibody, in eight patients with severe asthma and active EGPA. Patients were recruited by the tertiary care center of Clinical Immunology and Allergy, University of Naples Federico II. The following outcomes were assessed before (T0), and after 6 (T6) and 12 months (T12) of mepolizumab treatment: Birmingham Vasculitis Activity Score (BVAS), prednisone intake, Sino-Nasal Outcome Test (SNOT-22), Total Endoscopic Polyp Score (TENPS), Asthma Control Test (ACT), Forced Expiratory Volume one second (FEV1)%, blood eosinophilia. BVAS score significantly decreased showing a sharp reduction in disease activity score. Clinical improvements in terms of sinonasal scores and asthma symptoms were observed, in parallel with a drastic drop in eosinophil blood count. Prednisone intake was significantly reduced. In two patients, asthma exacerbations led to discontinuation in mepolizumab therapy after 6 and 12 months despite BVAS reduction. Mepolizumab treatment was well tolerated, and no severe adverse drug effects were registered. In conclusion, our 12-month real-life study suggests that mepolizumab may be beneficial and safe in active EGPA patients by improving disease activity score, sinonasal and asthma outcomes while reducing the burden of prednisone intake.
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http://dx.doi.org/10.1186/s12931-021-01775-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220666PMC
June 2021

Episodic Angioedema with Hypereosinophilia (Gleich's Syndrome): A Case Report and Extensive Review of the Literature.

J Clin Med 2021 Apr 1;10(7). Epub 2021 Apr 1.

Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), WAO Center of Excellence, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy.

Episodic angioedema with eosinophilia (EAE) (Gleich's syndrome) is a rare disease characterized by hypereosinophilia (up to 95 × 10 cells/L), recurrent episodes of angioedema, urticaria, weight gain, and fever, that occur at periodical intervals (usually every 3-4 weeks). The exact etiology of EAE is still unclear, but both eosinophils and abnormalities of cytokines homeostasis seem to play a pivotal role in the pathogenesis of the disease. In particular, the cyclic elevation of serum interleukin-5 before the increase in eosinophil count has been reported. Herein, we performed a broad literature review and report the case of a thirty-two-year-old woman with a two-year history of cyclic angioedema attacks, urticaria, periodic weight gain, and severe hypereosinophilia, diagnosed with EAE and treated with oral corticosteroids. Describing the most relevant clinical features of EAE reported so far in the literature, we aim to provide physicians with some useful tools to help them deal with this disease. In addition, we aim to raise awareness about this rare condition in which approved diagnostic classification criteria are currently missing.
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http://dx.doi.org/10.3390/jcm10071442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037656PMC
April 2021

Respiratory Manifestations in Primary Immunodeficiencies: Findings From a Pediatric and Adult Cohort.

Arch Bronconeumol (Engl Ed) 2021 Feb 5. Epub 2021 Feb 5.

Department of Translational Medical Sciences - Section of Pediatrics, University of Naples Federico II, Naples, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.arbres.2021.01.019DOI Listing
February 2021

Immunosuppressive Treatment in Antiphospholipid Syndrome: Is It Worth It?

Biomedicines 2021 Feb 1;9(2). Epub 2021 Feb 1.

Department of Translational Medical Sciences, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy.

The antiphospholipid syndrome (APS) is characterized by the development of venous and/or arterial thrombosis and pregnancy morbidity in patients with persistent antiphospholipid antibodies (aPL). Catastrophic antiphospholipid syndrome (CAPS) is a life-threatening form of APS occurring in about 1% of cases. Lifelong anticoagulation with vitamin K antagonists remains the cornerstone of the therapy for thrombotic APS, but frequently the use of anticoagulation may be problematic due to the increased risk of bleeding, drug interactions, or comorbidities. Immunosuppressant drugs are widely used to treat several autoimmune conditions, in which their safety and effectiveness have been largely demonstrated. Similar evidence in the treatment of primary APS is limited to case reports or case series, and studies on a large scale lack. Immunomodulatory drugs may be an emerging tool in managing such particular situations, like refractory obstetrical complications, CAPS, or so-called APS non-criteria manifestations. In addition, immunomodulatory drugs may be useful in patients experiencing recurrent thromboembolic events despite optimized anticoagulant therapy. We did a comprehensive review of literature analyzing the possible role of immunomodulation in primary APS to provide a broad overview of potentially safe and effective target treatments for managing this devastating disease.
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http://dx.doi.org/10.3390/biomedicines9020132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911562PMC
February 2021

Psychological processes in the experience of hereditary angioedema in adult patients: an observational study.

Orphanet J Rare Dis 2021 01 9;16(1):23. Epub 2021 Jan 9.

Department of Humanities, University "Federico II", Naples, Italy.

Background: Hereditary angioedema associated to C1 inhibitor deficiency (C1-INH-HAE) is a pathological condition characterized by episodes of subcutaneous swelling and it is frequently associated with discomfort and social impairment of the patients, due to the anxiety experienced for an unpreventable manifestation of an attack during daily life. In children increased level of stress and alexithymia have been associated to C1-INH-HAE, and the latter correlated also with the severity of the disease. We hypothesized that the involvement of psychological issues may impact on the severity of C1-INH-HAE in adult patients as well, interfering with their ability to engage with the management of the disease.

Methods: 28 adult patients with C1-INH-HAE were evaluated for clinical (C1-INH-HAE Severity Score) and psychological factors (alexithymia, emotion regulation, stress, patient health engagement, general severity index) by means of validated questionnaires.

Results: Mean age (standard deviation [SD]) was 45 (11) years and time from diagnosis was 20 (12) years. The mean C1-INH-HAE severity score was 6.4. Alexithymia was absent in 22 (78%) patients. Moderate and high stress levels were present in 17 (61%) and 4 (14%) patients, respectively. Moderate-high discomfort was experienced by 9 (36%) patients and a discomfort beyond the clinical attention threshold was shown by 3 (12%) patients. Stress correlated with patient health engagement and with psychological discomfort.

Conclusions: In C1-INH-HAE, patients health engagement and moderate-high psychological discomfort are linked with stress but not with the severity of the disease or alexithymia. A better patient health engagement may be a target for psychological intervention in clinics to ameliorate the stress perceived by C1-INH-HAE patients.
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http://dx.doi.org/10.1186/s13023-020-01643-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796642PMC
January 2021

Psychology and hereditary angioedema: A systematic review.

Allergy Asthma Proc 2021 01;42(1):e1-e7

From the Department of Humanities, University Federico II, Naples, Italy, and.

Hereditary angioedema (HAE) is caused by mutations in the C1 inhibitor (C1-INH) gene Serpin Family G Member 1(), which results in either the decreased synthesis of normal C1-INH (C1-INH-HAE type I) or expression of unfunctional C1-INH (C1-INH-HAE type II). In recent studies, emotional stress was reported by patients as the most common trigger factor for C1-INH-HAE attacks. Moreover, patients reported considerable distress over the significant variability and uncertainty with which the disease manifests, in addition to the impact of physical symptoms on their overall quality of life. We did a systematic review of the literature to shed light on the advancements made in the study of how stress and psychological processes impact C1-INH-HAE. All of the articles on C1-INH-HAE were analyzed up to December 2019. Both medical data bases and psychological data bases were examined. The keywords (KWs) used for searching the medical and psychological data bases were the following: "hereditary angioedema," "psychology," "stress," "anxiety," and "depression." Of a total of 2549 articles on C1-INH-HAE, 113 articles were retrieved from the literature search by using the related KWs. Twenty-one of these articles were retrieved, examined, and classified. Although the literature confirmed that stress may induce various physical diseases, it also warned against making simplistic statements about its incidence that did not take into account the complexity and multicausality of factors that contribute to C1-INH-HAE expression.
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http://dx.doi.org/10.2500/aap.2021.42.200073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768073PMC
January 2021

Role of Endothelial G Protein-Coupled Receptor Kinase 2 in Angioedema.

Hypertension 2020 11 8;76(5):1625-1636. Epub 2020 Sep 8.

Department of Medicine and Surgery (M.R., M.O., M.C.), University of Salerno, Italy.

Excessive BK (bradykinin) stimulation is responsible for the exaggerated permeabilization of the endothelium in angioedema. However, the molecular mechanisms underlying these responses have not been investigated. BK receptors are Gq-protein-coupled receptors phosphorylated by GRK2 (G protein-coupled receptor kinase 2) with a hitherto unknown biological and pathophysiological significance. In the present study, we sought to identify the functional role of GRK2 in angioedema through the regulation of BK signaling. We found that the accumulation of cytosolic Ca in endothelial cells induced by BK was sensitive to GRK2 activity, as it was significantly augmented by inhibiting the kinase. Accordingly, permeabilization and NO production induced by BK were enhanced, as well. In vivo, mice with reduced GRK2 levels in the endothelium (Tie2-CRE/GRK2) exhibited an increased response to BK in terms of vascular permeability and extravasation. Finally, patients with reduced GRK2 levels displayed a severe phenotype of angioedema. Taken together, these findings establish GRK2 as a novel pivotal regulator of BK signaling with an essential role in the pathophysiology of vascular permeability and angioedema.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544666PMC
November 2020

Gastrointestinal manifestations of angioedema: a potential area of misdiagnosis.

Eur J Gastroenterol Hepatol 2021 06;33(6):787-793

Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), WAO Center of Excellence.

Abdominal pain is one of the most common conditions leading people to the emergency department. An uncommon but well described cause of abdominal pain is angioedema of the gastrointestinal tract due to recurrent angioedema without wheals. Abdominal involvement is very common in hereditary angioedema (HAE), but it is also described in acquired angioedema and allergic forms. In patients with HAE, the involvement of gastrointestinal tract with resultant abdominal pain occurs in 43-93% of cases. Attacks can involve the entire gastrointestinal tract, such as the oropharynx, small intestine, colon, liver, or pancreas. Pain is the most common gastrointestinal symptom, and it may occur for many years even without cutaneous or respiratory symptoms. The case report we included in this article emphasizes the importance of accurate evaluation of personal and family history in patients with a long history of acute, severe, and unexplained abdominal pain, and it gives an example of how diagnostic delay may be longer if gastroenterological symptoms are the predominant clinical presentation. Furthermore, sometimes the simultaneous presence of concomitant gastrointestinal disorders and HAE may cause difficulties in differential diagnosis. Gastroenterologists and other physicians should add HAE to their list of potential causes of unexplained abdominal pain. The initiation of appropriate prophylaxis and treatment will prevent needless suffering and useless surgical and medical procedures.
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http://dx.doi.org/10.1097/MEG.0000000000001848DOI Listing
June 2021

Total and High Molecular Weight Adiponectin Expression Is Decreased in Patients with Common Variable Immunodeficiency: Correlation with Ig Replacement Therapy.

Front Immunol 2017 31;8:895. Epub 2017 Jul 31.

Department of Translational Medical Sciences, Allergy and Clinical Immunology, University of Naples Federico II, Naples, Italy.

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 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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http://dx.doi.org/10.3389/fimmu.2017.00895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5534466PMC
July 2017

Delay in diagnosis affects the clinical outcome in a cohort of cvid patients with marked reduction of iga serum levels.

Clin Immunol 2017 07 25;180:1-4. Epub 2017 Mar 25.

Department of Translational Medical Sciences, Allergy and Clinical Immunology, University of Naples Federico II, Naples, Italy.

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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http://dx.doi.org/10.1016/j.clim.2017.03.011DOI Listing
July 2017
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