Dott.ssa Francesca Angelotti

Dirigente Medico in Medicina Interna

Specializzazione in Immunologia Clinica e Allergologia

Iscrizione Albo Ordine dei Medici

Laurea in Medicina e Chirurgia

Long-term efficacy, safety, and tolerability of recombinant human hyaluronidase-facilitated subcutaneous infusion of immunoglobulin (Ig) (fSCIG; HYQVIA(®)) in immunodeficiency diseases: real-life data from a monocentric experience

Autori: Francesca Angelotti, Riccardo Capecchi, Daiana Giannini, Ornella Mazzarella, Valeria Rocchi, Paola Migliorini
Rivista: Clinical and Experimental Medicine
Abstract: Humoral immunodeficiency diseases represent a heterogeneous group of disorders that require long-term therapies. Thus, the treatment provided must not only be effective but also safe and well tolerated. In this paper, we report our data on the efficacy, safety, and tolerability of recombinant human hyaluronidase-facilitated subcutaneous infusion of immunoglobulin (Ig) (fSCIG; HyQvia(®)) in immunodeficiency patients. We collected retrospective data from 30 patients with primary and secondary immunodeficiency diseases in therapy with fSCIG from September 2014 to December 2019. We evaluated the efficacy of the therapy, taking into account serum IgG values during follow-up and the number of annual infectious events and serious bacterial infections reported by patients. Safety was assessed on the basis of the number and intensity of adverse events (AEs) and local reactions reported. Our real-life data suggest that long-term repeated self-administration of recom- binant human hyaluronidase-facilitated subcutaneous infusion of immunoglobulins results in a reduced rate of infectious events if compared to the pre-treatment rate. Both AEs and local reactions are mild to moderate and were never reasons for treatment discontinuation. Therapy with HyQvia shows prolonged efficacy and good tolerability; these aspects, together with the possibility of self-administration at home, minimize the impact the illness has on patients.
Keywords: Subcutaneous immunoglobulins · Immunodeficiency diseases · Hyaluronidase

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Fingerprinting of anti-alpha enolase antibodies in systemic sclerosis.

Autori: Perconti, Pratesi, Angelotti, Manca, Puxeddu, Rubino, Maranto, Giallongo, Migliorini
Rivista: Clin Exp Rheumatol. 2019 Dec 16
Abstract:
OBJECTIVES:
Anti-alpha enolase antibodies have been detected in systemic sclerosis (SSc), but little is known on their fine specificity and their predictive value on single disease manifestations. The aim of this work is to perform an epitope mapping of alpha enolase by means of truncated recombinant proteins and to analyse the clinico-serological correlations of anti-alpha enolase antibodies in SSc patients.
METHODS:
Thirty-eight SSc patients were recruited and fully clinically and serologically characterised. Plasmids encoding full length and truncated polypeptides of alpha enolase were generated; the polypeptides were purified under native conditions and used in dot blot to test sera from SSc patients and controls. The densitometric values obtained on all the polypeptides with anti-IgG subclass specific antibodies were analysed by cluster analysis and partial least square regression.
RESULTS:
Anti-alpha enolase antibodies (mostly IgG1 and IgG2) are detected in 47% of SSc patients. IgG1 target the amino terminal region of alpha enolase, while IgG2 are more restricted to the central portion of the molecule. Anti-alpha enolase antibodies are not associated with disease-specific antibodies or with interstitial lung disease and do not identify patients affected by the limited vs. diffuse form.
CONCLUSIONS:
Anti-alpha enolase antibodies are very frequent in SSc but are not associated with clinical or serological features of the disease. Further studies on larger cohorts of patients are necessary to define their possible contribution in defining specific subsets of the disease.

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Biomarkers In Chronic Spontaneous Urticaria: Current Targets And Clinical Implications

Autori: Ilaria Puxeddu, Fiorella Petrelli, Francesca Angelotti, Cristina Croia, and Paola Migliorini
Rivista: J Asthma Allergy. 2019; 12: 285–295. Published online 2019 Sep 20. doi: 10.2147/JAA.S184986
Abstract: Chronic urticaria (CU) is a mast cell-driven disease characterized by the development of wheals, angioedema, or both for more than 6 weeks. The two major sub-types are chronic spontaneous urticaria (CSU) and inducible urticaria. In the last decade different pathophysiological mechanisms, potentially responsible for the development of the disease, have been described. It is likely that the activation of mast cells and basophils in CSU can be the results of immune system dysregulation, activation of the inflammatory cascade, and of the extrinsic coagulation pathway. Some of the mediators involved in the pathophysiological mechanisms of CSU have recently been identified as potential biomarkers useful for the diagnosis, follow-up, and management of the disease, even if they are not yet available in clinical practice. Thus, in this review we discuss new insights in the mediators involved in the pathogenesis of CSU, highlighting their potential role as biomarkers in the activity and progression of the disease and response to therapies.
Keywords: chronic urticaria, inflammation, biomarkers, angiogenesis

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AB0624 Safety of Rituximab Biosimilar for the Treatment of Cryoglobulinemic Vasculitis

Autori: Caterina Vacchi, Marcella Visentini, Maria DI Cicco, Francesca Angelotti, Gianfranco Lauletta, Andreina Manfredi, Davide Filippini, Antonio Tavoni, Milvia Casato, Laura Castelnovo, Giuseppe Monti, Maurizio Pietrogrande, Carlo Salvarani, Massimo Galli, Marco Sebastiani
Rivista: Annals of the Rheumatic Diseases 78 (Suppl 2):1773.1-1773· June 2019.
Abstract: Rituximab (RTX) represents a milestone in the treatment of mixed cryoglobulinemic vasculitis (MCV). Despite usually well-tolerated, RTX may induce different types of adverse drug reactions, including exacerbation of vasculitis. RTX biosimilars have been recently approved in Europe in the treatment of rheumatoid arthritis, but no data are available about effectiveness and safety of RTX biosimilars in the treatment of MCV.

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THU0453 Efficacy of ab initio or very early introduction of immunosuppressive therapy in giant cell arteritis: a multicenter retrospective observational study

Autori: L. Quartuccio, E. Cavallaro, F. Angelotti, R. Capecchi, G. Vitiello, D. Cammelli, A. Tavoni, S. De Vita
Rivista: Annals of the Rheumatic Diseases 77 (Suppl 2) · June 2018. doi: 10.1136/annrheumdis-2018-eular.3794
Abstract: Glucocorticoids (GC) remain the mainstay of treatment of giant cell arteritis (GCA). However, relapses occur in up to 50% of patients when GC are tapered and prolonged courses of GC are associated with serious side effects. In this setting, the outcome is frequently determined by GC-related adverse events (AEs). Thus, several studies have been conducted on the effectiveness of a GC-sparing immunosuppressive therapy (IT), with conflicting results.

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IL-1 family cytokines and soluble receptors in systemic lupus erythematosus

Autori: Paola Italiani, Maria Laura Manca, Francesca Angelotti, Daniela Melillo, Federico Pratesi, Ilaria Puxeddu, Diana Boraschi & Paola Migliorini
Rivista: Arthritis Research & Therapy. 2018 Feb 8;20(1):27. doi: 10.1186/s13075-018-1525-z.
Abstract:
BACKGROUND:
Dysregulated production of cytokines has a critical role in systemic lupus. The aim of this work is to identify, by a comprehensive analysis of IL-1 family cytokines and receptors in serum, correlation between cytokines/receptors' levels and the clinical and serological features of the disease.
METHODS:
A full clinical evaluation was performed in 74 patients with systemic lupus erythematosus (SLE). C3, C4, anti-dsDNA and anti-C1q antibodies were measured. Cytokines of the IL-1 family (IL-1α, IL-1β, IL-33, IL-18), soluble receptors (sIL-1R1, sIL-1R2, sIL-1R3, ST2/sIL-1R4) and antagonists (IL-1Ra, IL-18 binding protein (IL-18BP)) were measured in serum by multiarray ELISA. Free IL-18 was calculated as the amount of IL-18 not inhibited by IL-18BP. Data were analysed by non-parametric tests and by multivariate analysis, using partial least squares (PLS) models.
RESULTS:
Total IL-18, IL-18BP, sIL-1R4 and IL-1Ra levels were higher in SLE vs.
CONTROLS:
Total and free IL-18 and sIL-1R4 were higher in patients with active vs. inactive disease and correlated with ECLAM, anti-C1q and anti-dsDNA antibodies. sIL-1R2 was higher in patients with inactive disease, was negatively correlated with ECLAM and anti-C1q antibodies and was positively correlated with C3 levels. PLS identified sIL-1R4, sIL-1R2 and anti-dsDNA as variables distinguishing patients with active from those with inactive disease; sIL-1R4, IL-18BP and anti-dsDNA identified patients with active nephritis; sIL-1R4, C3, IL-18 and free IL-18 identified patients with haematological involvement.
CONCLUSION:
The data support the use of IL-18, sIL-1R2 and sIL-1R4 as biomarkers of disease activity and organ involvement, and suggest that failure in the inhibition of IL-1 activation may be a critical event in the active stages of SLE.
Keywords: Biomarkers; Il-1 family; Soluble IL-1 family receptors; Systemic lupus erythematosus

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One year in review 2017: Pathogenesis of rheumatoid arthritis

Autori: Angelotti F, Parma A, Cafaro G, Capecchi R, Alunno A, Puxeddu I
Rivista: Clin Exp Rheumatol. 2017 May-Jun;35(3):368-378. Epub 2017 Jun 7. Review.
Abstract: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease influenced by both genetic and environmental factors. It has been postulated that a high-risk genetic background, in combination with epigenetic marks and environmental exposures, leads to a cascade of events inducing synovitis and consequent destructive arthritis. The clinical picture of joint involvement in RA is the result of chronic inflammation of the synovium, characterised by interactions of resident cells such as fibroblast-like synoviocytes (FLS) with cells of the innate (e.g. macrophages, dendritic cells, mast cells and NK cells, neutrophils) and adaptive immune system (e.g. B and T lymphocytes). Currently, our understanding of the role of innate and adaptive immunity in the pathogenesis of RA is expanding. The concept of how immune responses contribute to the disease has dramatically evolved over the last 50 years. Shedding some light on the different aspects of RA pathogenesis will help to identify new targets for the development of disease-modifying therapies. Thus, in this review we report new insights in RA pathogenesis, resulting from a literature research date published in the last year.

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A novel DNA/histone H4 peptide complex detects autoantibodies in systemic lupus erythematosus sera

Autori: Panza F, Alcaro MC, Petrelli F, Angelotti F, Pratesi F, Rovero P and Migliorini P.
Rivista: Arthritis Res Ther. 2016; 18: 220. Published online 2016 Oct 4. doi: 10.1186/s13075-016-1117-8
Abstract:
BACKGROUND:
The detection of anti-dsDNA antibodies is critical for the diagnosis and follow-up of systemic lupus erythematosus (SLE) patients. The presently available assays are characterized by a non-optimal specificity (solid phase assays) or sensitivity (Crithidia Luciliae immunofluorescence test (CLIFT)). To overcome the limits of CLIFT and solid phase chromatin assays, we explored the diagnostic potential of an assay based on plasmid DNA containing a highly bent fragment of 211 bp from Crithidia Luciliae minicircles, complexed with histone peptides.
METHODS:
Electrically neutral complexes of PK201/CAT plasmid (PK) DNA and histone 4 (H4) peptides were evaluated by electromobility shift assay. Complexes of H4 peptides and PK were absorbed to the solid phase to detect specific immunoglobulin G (IgG) in sera. Sera from 109 SLE patients, 100 normal healthy subjects, and 169 disease controls were tested.
RESULTS:
H4(14-34) containing the consensus sequence for DNA binding interacts with PK, retarding its migration. H4(14-34)/PK complexes were used to test sera by ELISA. Anti-H4-PK antibodies were detected in 56 % of SLE sera (more frequently in patients with skin or joint involvement) versus 5.9 % in disease controls; inhibition assays show that sera react with epitopes present on DNA or on the complex, not on the peptide. Antibody titer is correlated with European Consensus Lupus Activity Measurement (ECLAM) score and anti-complement component 1q (C1q) antibodies, negatively with C3 levels. Anti-H4-PK antibodies compared with CLIFT and solid phase dsDNA assays display moderate concordance.
CONCLUSIONS:
The H4/PK assay is a simple and reliable test which is useful for the differential diagnosis and evaluation of disease activity in SLE patients.

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Severe thrombocytopenic purpura after meningococcal C vaccination in a woman affected by systemic lupus erythematosus

Autori: Angelotti F., Tavoni A.
Rivista: Clin Exp Rheumatol. 2017 Jan-Feb;35(1):172. Epub 2016 Sep 7

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AB0500 A Novel DNA-Peptide Complex Detects Anti-DSDNA Antibodies in SLE Sera

Autori: P. Migliorini, F. Panza, M.C. Alcaro, F. Petrelli, F. Angelotti, F. Pratesi, P. Rovero
Rivista: Annals of the Rheumatic Diseases. 2016
Abstract:
Background:
The detection of anti-dsDNA antibodies is critical for the diagnosis and follow-up of SLE patients. The presently available assays are characterized by a non-optimal specificity (solid phase assays) or sensitivity (CLIF test).
Objectives
To overcome the limits of CLIFT and solid phase chromatin assays, we explored the diagnostic potential of an assay based on plasmid DNA containing a highly bent fragment of 211 bp from Crithidia Luciliae microcircles, complexed with histone peptides.
Methods
Electrically neutral complexes of PK201/CAT plasmid (PK) DNA and histone (H) 4 peptides were evaluated by electromobility shift assay. Complexes of H4 peptides and PK were absorbed to the solid phase to detect IgG antibodies in sera. Sera from 109 SLE patients, 100 normals and 69 disease controls (systemic sclerosis, Sjogren's syndrome, unclassified connective tissue disease) were tested.
Results
H4 (14–34) containing the consensus sequence for DNA binding interacts with PK retarding its migration. H4 (14–34)-PK complexes were used to test sera by ELISA; inhibition assays show that sera react with epitopes present on DNA or on the complex, not on the peptide. Anti-H4-PK antibodies were detected in 56% SLE sera (more frequently in patients with skin or joint involvement) vs 12% disease controls; antibody titer is correlated with ECLAM score and anti-C1q antibodies, negatively with C3 levels. Anti-H4-PK antibodies compared with CLIFT and solid phase dsDNA assays display moderate concordance.
Conclusions
The H4-PK assay is a simple and reliable test, endowed with high specificity and sensitivity, useful for the differential diagnosis and evaluation of disease activity of SLE patients. This assay increases the variety of anti-DNA antibodies that can be measured, complementing the assays currently used for the detection of anti-DNA antibodies.

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