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Article ; Online: Affecting the effectors: JAK inhibitors modulation of immune cell numbers and functions in patients with rheumatoid arthritis.

Garufi, Cristina / Maclean, Mary / Gadina, Massimo / Spinelli, Francesca Romana

2022 Volume 18, Issue 3, Page(s) 309–319

Abstract: Introduction: The Janus kinase family includes four members - JAK1, JAK2, JAK3, TYK2 - that are selectively associated with type I and II cytokine receptors. Jak-inhibitors (Jakinibs) are a new class of drugs for treating inflammatory diseases. Five ... ...

Abstract	Introduction: The Janus kinase family includes four members - JAK1, JAK2, JAK3, TYK2 - that are selectively associated with type I and II cytokine receptors. Jak-inhibitors (Jakinibs) are a new class of drugs for treating inflammatory diseases. Five Jakinibs are currently available for Rheumatoid Arthritis (RA): tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib. Considering the role of cytokines and growth factors in immune cell survival and activation, the anti-proliferative and suppressive effects of Jakinibs on these cells are predictable. Areas covered: This review summarizes Jakinibs' effects on immune populations Expert opinion: In vitro
MeSH term(s)	Antirheumatic Agents/therapeutic use ; Arthritis, Rheumatoid/drug therapy ; Cell Count ; Humans ; Janus Kinase Inhibitors/therapeutic use ; Janus Kinases
Chemical Substances	Antirheumatic Agents ; Janus Kinase Inhibitors ; Janus Kinases (EC 2.7.10.2)
Language	English
Publishing date	2022-02-25
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2274260-8
ISSN	1744-8409 ; 1744-666X
ISSN (online)	1744-8409
ISSN	1744-666X
DOI	10.1080/1744666X.2022.2042254
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Article ; Online: Exercise-induced modulation of Interferon-signature: a therapeutic route toward management of Systemic Lupus Erythematosus.

Spinelli, Francesca Romana / Berti, Riccardo / Farina, Gabriele / Ceccarelli, Fulvia / Conti, Fabrizio / Crescioli, Clara

Autoimmunity reviews

2023 Volume 22, Issue 10, Page(s) 103412

Abstract: Systemic Lupus Erythematosus (SLE) is a multisystemic autoimmune disorder characterized by flares-ups/remissions with a complex clinical picture related to disease severity and organ/tissue injury, which, if left untreated, may result in permanent damage. ...

Abstract	Systemic Lupus Erythematosus (SLE) is a multisystemic autoimmune disorder characterized by flares-ups/remissions with a complex clinical picture related to disease severity and organ/tissue injury, which, if left untreated, may result in permanent damage. Enhanced fatigue and pain perception, worsened quality of life (QoL) and outcome are constant, albeit symptoms may differ. An aberrant SLE immunoprofiling, note as "interferon (IFN)α-signature", is acknowledged to break immunotolerance. Recently, a deregulated "IFNγ-signature" is suggested to silently precede/trigger IFNα profile before clinical manifestations. IFNα- and IFNγ-over-signaling merge in cytokine/chemokine overexpression exacerbating autoimmunity. Remission achievement and QoL improvement are the main goals. The current therapy (i.e., corticosteroids, immunosuppressants) aims to downregulate immune over-response. Exercise could be a safe treatment due to its ever-emerging ability to shape and re-balance immune system without harmful side-effects; in addition, it improves cardiorespiratory capacity and musculoskeletal strength/power, usually impaired in SLE. Nevertheless, exercise is not yet included in SLE care plans. Furthermore, due to the fear to worsening pain/fatigue, SLE subjects experience kinesiophobia and sedentary lifestyle, worsening physical health. Training SLE patients to exercise is mandatory to fight inactive behavior and ameliorate health. This review aims to focus the attention on the role of exercise as a non-pharmacological therapy in SLE, considering its ability to mitigate IFN-signature and rebalance (auto)immune response. To this purpose, the significance of IFNα- and IFNγ-signaling in SLE etiopathogenesis will be addressed first and discussed thereafter as biotarget of exercise. Comments are addressed on the need to make aware all SLE care professional figures to promote exercise for health patients.
MeSH term(s)	Humans ; Quality of Life ; Interferon-alpha/therapeutic use ; Cytokines/therapeutic use ; Lupus Erythematosus, Systemic/drug therapy ; Autoimmunity
Chemical Substances	Interferon-alpha ; Cytokines
Language	English
Publishing date	2023-08-18
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2144145-5
ISSN	1873-0183 ; 1568-9972
ISSN (online)	1873-0183
ISSN	1568-9972
DOI	10.1016/j.autrev.2023.103412
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Article: Telemedicine for rheumatological consultation: the new semeiotics for rheumatic examination.

Spinelli, Francesca Romana / Govoni, Marcello / Iannone, Florenzo / Mosca, Marta / Cauli, Alberto / Frediani, Bruno / Caporali, Roberto / Conti, Fabrizio

Clinical and experimental rheumatology

2023 Volume 41, Issue 5, Page(s) 993–996

MeSH term(s)	Humans ; Rheumatology ; Rheumatic Diseases/diagnosis ; Rheumatic Diseases/therapy ; Referral and Consultation ; Telemedicine
Language	English
Publishing date	2023-03-27
Publishing country	Italy
Document type	Editorial
ZDB-ID	605886-3
ISSN	1593-098X ; 0392-856X
ISSN (online)	1593-098X
ISSN	0392-856X
DOI	10.55563/clinexprheumatol/eeexhg
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Article ; Online: Tapering and discontinuation of glucocorticoids in patients with rheumatoid arthritis treated with tofacitinib.

Spinelli, Francesca Romana / Garufi, Cristina / Mancuso, Silvia / Ceccarelli, Fulvia / Truglia, Simona / Conti, Fabrizio

Scientific reports

2023 Volume 13, Issue 1, Page(s) 15537

Abstract: Although the rapid onset of effect of glucocorticoids (GCs) allows rapid control of rheumatoid arthritis (RA) symptoms, their chronic use may be associated with several adverse events. The 2022 update of EUALR recommendations for the management of ... ...

Abstract	Although the rapid onset of effect of glucocorticoids (GCs) allows rapid control of rheumatoid arthritis (RA) symptoms, their chronic use may be associated with several adverse events. The 2022 update of EUALR recommendations for the management of patients with RA suggests to reduce and discontinue oral GCs as quickly as possible. Considering GCs as a "bridging therapy" to promptly reduce symptoms and control inflammation, fast-acting drugs such as tofacitinib could allow faster and safer tapering of GCs. The purpose of this pilot study was to evaluate the steroid-sparing effect of adding tofacitinib in patients with RA inadequately responsive to methotrexate taking concomitant GCs. In this open-label pilot study, we enrolled patients with moderate to severe RA on a stable dose of prednisone (5-12.5 mg/day) who started treatment with tofacitinib. After 1 month, in patients who achieved at least a moderate EULAR response (decrease of > 1.2 in DAS28_CRP), GCs was tapered according to a predetermined schedule until complete discontinuation at week 12. Disease activity was assessed after 4, 12, 24 and 48 weeks of treatment. The primary endpoint was the percentage of patients discontinuing GCs after 12 weeks of tofacitinib treatment. We enrolled 30 patients (26 F: 4 M, mean age 60 ± 13 years, mean disease duration 13.2 ± 7.8 years). The primary endpoint was achieved: 9 patients (30%) discontinued GCs at week-12. At week-24, other 12 patients (46%) withdrew GCs. The median prednisone dose decreased from 5 mg/day (interquartile range 5-10 mg) to 2.5 (0-5) mg/day at week 12 and 48 (p < 0.00001 vs baseline). At week 48, 12 out of 30 patients (40%) had discontinued prednisone. The percentage of patients achieving remission or low disease activity increased throughout the follow-up without any difference between patients who discontinued or not the GC. In this cohort of long-standing RA patients treated with tofacitinib, the discontinuation of glucocorticoids was achievable in up to 30% of patients. These results should encourage rheumatologists to consider GCs tapering and discontinuation of GCs, as suggested by the 2022 EULAR recommendations, an achievable goal.
MeSH term(s)	Humans ; Middle Aged ; Aged ; Glucocorticoids/adverse effects ; Prednisone/adverse effects ; Pilot Projects ; Arthritis, Rheumatoid/drug therapy
Chemical Substances	Glucocorticoids ; Prednisone (VB0R961HZT) ; tofacitinib (87LA6FU830)
Language	English
Publishing date	2023-09-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-42371-z
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Article ; Online: JAK1: Number one in the family; number one in inflammation?

Spinelli, Francesca Romana / Colbert, Robert A / Gadina, Massimo

Rheumatology (Oxford, England)

2021 Volume 60, Issue Suppl 2, Page(s) ii3–ii10

Abstract: Several cytokines involved in inflammatory pathologies signal via the Janus kinase-signal transducer and activator of transcription pathway. Four JAKs are known: JAK1, JAK2, JAK3 and TYK2. The specific activation of JAKs and STATs determines the ... ...

Abstract	Several cytokines involved in inflammatory pathologies signal via the Janus kinase-signal transducer and activator of transcription pathway. Four JAKs are known: JAK1, JAK2, JAK3 and TYK2. The specific activation of JAKs and STATs determines the biological effects of each cytokine. JAK1 is involved in the signalling of 'γc' receptor cytokines (IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21), pro-inflammatory cytokines including IL-6, as well as IFN. The critical position of JAK1 downstream of these cytokines suggests that JAK1-selective inhibitors are comparable to non-selective ones, without the unwanted consequences of JAK2- or JAK3-blockade. JAK inhibition has led to a better understanding of the biology of synovial inflammation and bone homeostasis. Moreover, the efficacy of non-selective JAK inhibitors and novel JAK1-selective drugs in RA supports a role for JAK1 in its pathogenesis. JAK1-selective drugs are also showing promise in axial spondyloarthritis, suggesting that they may target additional regulatory pathways that impact cytokines such as TNF and IL-17A, which do not use JAKs. Additionally, evidence now supports a JAK1 predominance in the signalling of IL-6 and oncostatin M, and indirectly, of TNF in synovial fibroblasts, macrophages and endothelial cells. Notably, bone homeostasis is also dependent on cytokines relying on JAK1 signalling to promote receptor activator of NF-κB ligand expression in osteoblasts and T cells, contributing to osteoclastogenesis. Here, the contribution of JAK1 over other kinases is unclear. While beneficial effects of JAK inhibitors on bone erosion are supported by preclinical and clinical data, effects on new bone formation in axial spondyloarthritis requires additional study.
MeSH term(s)	Arthritis, Rheumatoid/drug therapy ; Arthritis, Rheumatoid/immunology ; Bone Resorption/immunology ; Cytokines/immunology ; Humans ; Janus Kinase 1/antagonists & inhibitors ; Janus Kinase 1/immunology ; Janus Kinase 2 ; Janus Kinase 3 ; Janus Kinase Inhibitors/therapeutic use ; Osteogenesis/immunology ; Spondylarthropathies/drug therapy ; Spondylarthropathies/immunology ; Synovitis/immunology ; TYK2 Kinase
Chemical Substances	Cytokines ; Janus Kinase Inhibitors ; Janus Kinase 1 (EC 2.7.10.2) ; Janus Kinase 2 (EC 2.7.10.2) ; Janus Kinase 3 (EC 2.7.10.2) ; TYK2 Kinase (EC 2.7.10.2)
Language	English
Publishing date	2021-04-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1464822-2
ISSN	1462-0332 ; 1462-0324
ISSN (online)	1462-0332
ISSN	1462-0324
DOI	10.1093/rheumatology/keab024
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Zs.B 240: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 497: Show issues

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Article ; Online: Comment on: Temporal relationships between systemic lupus erythematosus and comorbidities.

Conti, Fabrizio / Ceccarelli, Fulvia / Spinelli, Francesca Romana

Rheumatology (Oxford, England)

2019 Volume 58, Issue 9, Page(s) 1698

MeSH term(s)	Comorbidity ; Humans ; Lupus Erythematosus, Systemic
Language	English
Publishing date	2019-07-10
Publishing country	England
Document type	Letter ; Comment
ZDB-ID	1464822-2
ISSN	1462-0332 ; 1462-0324
ISSN (online)	1462-0332
ISSN	1462-0324
DOI	10.1093/rheumatology/kez271
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Article ; Online: HiJAKing SARS-CoV-2? The potential role of JAK inhibitors in the management of COVID-19.

Spinelli, Francesca Romana / Conti, Fabrizio / Gadina, Massimo

Science immunology

2020 Volume 5, Issue 47

Abstract: JAK kinase inhibitors are being investigated as a way of managing cytokine storm in severe COVID-19 patients. ...

Abstract	JAK kinase inhibitors are being investigated as a way of managing cytokine storm in severe COVID-19 patients.
MeSH term(s)	Animals ; Azetidines/therapeutic use ; Betacoronavirus/physiology ; Clinical Trials as Topic ; Coronavirus Infections/drug therapy ; Coronavirus Infections/immunology ; Humans ; Janus Kinase Inhibitors/therapeutic use ; Pandemics ; Pneumonia, Viral/drug therapy ; Pneumonia, Viral/immunology ; Sulfonamides/therapeutic use
Chemical Substances	Azetidines ; Janus Kinase Inhibitors ; Sulfonamides ; baricitinib (ISP4442I3Y)
Keywords	covid19
Language	English
Publishing date	2020-05-08
Publishing country	United States
Document type	Journal Article
ISSN	2470-9468
ISSN (online)	2470-9468
DOI	10.1126/sciimmunol.abc5367
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Article ; Online: Foreword: Seminars in Research 2014 Joint Experiences in Rheumatology and Dermatology.

Costanzo, Antonio / Spinelli, Francesca Romana

The Journal of international medical research

2016 Volume 44, Issue 1 suppl, Page(s) 3–5

Language	English
Publishing date	2016-09
Publishing country	England
Document type	Journal Article
ZDB-ID	184023-x
ISSN	1473-2300 ; 0300-0605 ; 0142-2596
ISSN (online)	1473-2300
ISSN	0300-0605 ; 0142-2596
DOI	10.1177/0300060515593267
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Zs.A 925: Show issues

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Article ; Online: JAK inhibitors: Ten years after.

Spinelli, Francesca Romana / Meylan, Françoise / O'Shea, John J / Gadina, Massimo

European journal of immunology

2021 Volume 51, Issue 7, Page(s) 1615–1627

Abstract: The European Journal of Immunology was launched 50 years ago, coinciding with the discovery of many cytokines and growth factors and the emergence of an entirely new field of research. Ultimately, our knowledge about the biological activity of these ... ...

Abstract	The European Journal of Immunology was launched 50 years ago, coinciding with the discovery of many cytokines and growth factors and the emergence of an entirely new field of research. Ultimately, our knowledge about the biological activity of these factors allowed us to better understand how the immune system functions in the context of inflammatory and autoimmune diseases leading to the development of targeted biologic therapies. The study of cytokine signal transduction led to the discovery of Janus kinases (JAK), and the consideration of therapeutically targeting JAKs to treat immune and inflammatory diseases. This year also marks the tenth anniversary of the approval of the first JAK inhibitor (jakinib) and now there are a total of nine approved jakinibs for treatment of rheumatologic, dermatologic, gastrointestinal, and neoplastic indications and most recently COVID-19. Here, we summarized the discoveries that led to development of first-generation jakinibs, discussed some of the newer, possibly more selective jakinibs, as well as jakinibs that also target other kinases. We also illustrated the rationale behind the application of these drugs in the treatment of COVID-19 cytokine storm. In this review, we will discuss the clinical success of jakinibs, the gaps in our understanding of their biological activities as well as challenges in regard to their clinical application.
MeSH term(s)	Autoimmune Diseases/drug therapy ; COVID-19/drug therapy ; Cytokine Release Syndrome/drug therapy ; Cytokine Release Syndrome/pathology ; Cytokines/biosynthesis ; Cytokines/immunology ; Humans ; Hypersensitivity/drug therapy ; Janus Kinase Inhibitors/therapeutic use ; Janus Kinases/antagonists & inhibitors ; SARS-CoV-2/drug effects ; Signal Transduction/immunology
Chemical Substances	Cytokines ; Janus Kinase Inhibitors ; Janus Kinases (EC 2.7.10.2)
Language	English
Publishing date	2021-05-31
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Review
ZDB-ID	120108-6
ISSN	1521-4141 ; 0014-2980
ISSN (online)	1521-4141
ISSN	0014-2980
DOI	10.1002/eji.202048922
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Zs.A 489: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Kidney Biopsy and Immuno-Rheumatological Diseases: A Retrospective and Observational Study.

Gigante, Antonietta / Cianci, Rosario / Villa, Annalisa / Pellicano, Chiara / Giannakakis, Konstantinos / Rosato, Edoardo / Spinelli, Francesca Romana / Basile, Umberto / Racco, Cosimo / Di Virgilio, Elena Maria / Cerbelli, Bruna / Conti, Fabrizio

Journal of personalized medicine

2024 Volume 14, Issue 1

Abstract: Renal involvement is a common occurrence in patients with immuno-rheumatological diseases (IRDs). Several instances of glomerulonephritis (GN) occur in the setting of IRD and complicate the clinical course of an underlying condition. The aim of this ... ...

Abstract	Renal involvement is a common occurrence in patients with immuno-rheumatological diseases (IRDs). Several instances of glomerulonephritis (GN) occur in the setting of IRD and complicate the clinical course of an underlying condition. The aim of this study was to observe the spectrum of nephropathies according to age, kidney function, history of IRD at the time of biopsy, and histopathological kidney diagnosis. We evaluated data relating to 699 consecutive kidney native biopsies (female 52.1%) with a median age of 48 years (IQR 34-62) performed in adult patients collected over 15 years. The study population was divided into three groups: patients with kidney histological findings correlated to underlying IRD (Group 1), patients with kidney histological findings not correlated to underlying IRD (Group 2), and patients with kidney histological findings compatible with "de novo" IRD (absent in personal medical history) (Group 3). Kidney involvement related to IRD was found in 25.2% of patients. Group 1 was mostly represented by lupus nephritis (76.6%), with a younger age than Group 3 (
Language	English
Publishing date	2024-01-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662248-8
ISSN	2075-4426
ISSN	2075-4426
DOI	10.3390/jpm14010092
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