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The William Harvey Research Institute - Faculty of Medicine and Dentistry

Dr Felice Rivellese

Felice

Research Fellow and Clinical Research Fellow in Rheumatology at Barts Health NHS Trust

Centre: Experimental Medicine & Rheumatology

Email: f.rivellese@qmul.ac.uk
Twitter: @FeliceRivellese

Profile

ORCiD: https://orcid.org/0000-0002-6759-7521

Researchgate 
Linkedin 

Felice Rivellese studied Medicine at the University of Naples Federico II. During the final years of his speciality training in Clinical Immunology, with the support of a EULAR bursary and of an ARTICULUM (now FOREUM) fellowship, he attended the Department of Rheumatology at Leiden University as a visiting research fellow, where he studied the involvement of cells of the innate immunity in the pathogenesis of inflammatory arthritis.

In 2014, he moved to the Centre of Experimental Medicine & Rheumatology at Queen Mary University of London, led by Prof Costantino Pitzalis, and he was awarded a Marie-Curie fellowship, with a project on the Study of Mast cells in Rheumatoid Arthritis, which was also the focus of his PhD in Clinical Pathophysiology and Experimental Medicine, with sub specialization in Immunological and Rheumatologic Sciences (PhD thesis).  

In 2018, he was awarded a Transitional Research Fellowship by the National Institute of Health Research (NIHR), with a project on the study of Synovial B cells to inform treatment response in Rheumatoid Arthritis (SyBRA). During this time, he transitioned from basic/laboratory research to clinical research, acquiring new skills in clinical trials, epidemiology, and bioinformatics, as he was actively involved in the setup, delivery, and analysis of stratified medicine clinical trials in inflammatory arthritis.

Currently, Dr Rivellese is responsible for the management of the EMR Clinical Research Team, where he is responsible for performing ultrasound-guided synovial biopsies and coordinates a team of 2 nurses, 3 clinical trial practitioners and 2 clinical fellows at PhD level. He is also affiliated to the Centre for Translational Bioinformatics, where he collaborates with Prof Michael Barnes and Dr Myles Lewis and their teams on several research projects in stratified medicine.

Dr Rivellese is member of the EULAR Council (European Alliance of Associations for Rheumatology). He is Past-Chair (2021-2022) of the EMEUNET (Emerging EULAR Network) Committee, and he is member of the EULAR Research Committee.

Research

Group members

Mile-End Clinical Research Team
Mary Githinji, Victoria Amosun (Research nurses)
Fatima Bibi, Ishraat Miah (Clinical Trial Practitioners)
Dr Susan Wang, Dr Sotiria Manou-Stathopoulou (Clinical Research Fellows)

Innate immunity and inflammatory arthritis

During the first years of my career, my research interests focused on the role of cells of the innate immunity, such as mast cells and basophils, in inflammatory arthritis. I showed that mast cells, best known as effector cells of hypersensitive (i.e. allergic) reactions,  infiltrate the joints of patients with Rheumatoid Arthritis, where they can induce the activation of B cells, leading to the production of autoantibodies (https://doi.org/10.1136/annrheumdis-2018-213418). On the other hand, I also found that mast cells, depending on the type of stimuli, can induce either pro- or anti-inflammatory responses responses (https://doi.org/10.1002/art.39192). Altogether, the results of my research suggest that mast cells can act as immunomodulatory cells (https://doi.org/10.1016/j.autrev.2017.04.001).

Stratified medicine clinical trials: from bench to bedside

Following the award of an NIHR Transitional Research fellowship, building on my expertise in basic and translational science, I aimed at transferring the results obtained in the laboratory to the clinical practice.

To this aim, I focused on the study of samples obtained from the joints of patients recruited in three large, stratified medicine trials in Rheumatoid Arthritis:

  • Patients with early untreated arthritis recruited into the Pathobiology of Early Arthritis Cohort (PEAC);
  • Patients in whom the first-line medication failed, recruited into the Stratification of biologic Therapies for RA by Pathobiology (STRAP);
  • Patients in whom the first biologic medication failed, recruited into the Randomised, open labelled study in anti-TNFa inadequate responders to investigate the mechanisms for Response - Resistance to Rituximab versus Tocilizumab in RA (R4RA)

A key output of my research has been the validation of the scores used to assess the presence of B cells in synovia, including immunohistochemistry techniques (e.g. looking at B cells under the microscope) and molecular analyses, the latter assessing a signature of genes highly specific for B cells (https://doi.org/10.1002/art.41184). Using the molecular score, the results of the R4RA trial, recently published in The Lancet, have shown that patients with a low B cell signature in the joints have a poor response to B cell depletion with Rituximab, as compared with Tocilizumab, the latter targeting the IL6 receptor (10.1016/S0140-6736(20)32341-2).

Current/future research

My current research is focused on expanding the above findings, by combining histology and molecular analyses to build integrated models to predict treatment response, an ongoing work in collaboration with the Centre for Translational Bioinformatics.

In parallel, I’m leading the analysis of the STRAP trial, where, building on the experience with the R4RA trial, we are combining histological and molecular approaches to study treatment response/non-response.

Our next step will be to combine the results from the above cohorts, which have been recruiting patients at different disease stages.  One of the next aims will be to dissect the mechanisms of non-response, by focusing on patients in whom multiple medications fail, i.e. patients with so-called Difficult-to-treat Rheumatoid Arthritis. In parallel, I’m also contributing to the setup of a new IMI-EU-funded multi-centre, biopsy-driven clinical trial (https://3tr-imi.eu/), that will recruit up to 400 patients to test the hypothesis that synovial biomarker-positive patients have a better response than biomarker-negative patients, thus providing the next step towards personalised medicine in inflammatory arthritis.

 

Key Publications

Full list: https://orcid.org/0000-0002-6759-7521

  • Boutet MA, Nerviani A, Lliso-Ribera G, Leone R, Sironi M, Hands R, Rivellese F, Del Prete A, Goldmann K, Lewis MJ, Mantovani A, Bottazzi B, Pitzalis C. Circulating and Synovial Pentraxin-3 (PTX3) Expression Levels Correlate With Rheumatoid Arthritis Severity and Tissue Infiltration Independently of Conventional Treatments Response. Front Immunol. 2021 Jun 25;12:686795. doi: https://doi.org/10.3389/fimmu.2021.686795
  • Kragstrup TW, Singh HS, Grundberg I, Nielsen AL, Rivellese F, Mehta A, Goldberg MB, Filbin MR, Qvist P, Bibby BM. Plasma ACE2 predicts outcome of COVID-19 in hospitalized patients. PLoS One. 2021 Jun 4;16(6):e0252799. doi:  10.1371/journal.pone.0252799
  • Rivellese F, Manou-Stathopoulou S, Mauro D, Goldmann K, Pyne D, Rajakariar R, Gordon P, Schafer P, Bombardieri M, Pitzalis C, Lewis MJ. Effects of targeting the transcription factors Ikaros and Aiolos on B cell activation and differentiation in systemic lupus erythematosus. Lupus Sci Med. 2021 Mar;8(1):e000445. doi:  https://doi.org/10.1136/lupus-2020-000445
  • Humby F, Durez P, Buch M, Lewis M, Rizvi H, Rivellese F, Nerviani A, Giorli G, Mahto A, Montecucco C, Lauwerys B, Ng N, Ho P, Bombardieri M, Romão VC, Verschueren P, Kelly S, Sainaghi PP, Gendi N, Dasgupta B, Cauli A, Reynolds P, Cañete JD, Moots R, Taylor P, Edwards CJ, Isaacs J, Sasieni P, Choy E, Pitzalis C. Rituximab versus Tocilizumab in anti-TNF inadequate responder 1 patients with Rheumatoid Arthritis (R4RA): a stratified, biopsy-driven, multi-centre, randomised, open label, controlled clinical trial – 16 week outcomes. Lancet. 2021 Jan 23;397(10271):305-317. doi:  10.1016/S0140-6736(20)32341-2 (IF 60.392)
  • Pontarini E, Murray-Brown WJ, Croia C, Lucchesi D, Conway J, Rivellese F, Fossati-Jimack L, Astorri E, Prediletto E, Corsiero E, Romana Delvecchio F, Coleby R, Gelbhardt E, Bono A, Baldini C, Puxeddu I, Ruscitti P, Giacomelli R, Barone F, Fisher B, Bowman SJ, Colafrancesco S, Priori R, Sutcliffe N, Challacombe S, Carlesso G, Tappuni A, Pitzalis C, Bombardieri M. Unique expansion of IL-21+ Tfh and Tph cells under control of ICOS identifies Sjögren's syndrome with ectopic germinal centres and MALT lymphoma. Ann Rheum Dis. 2020 Dec;79(12):1588-1599. doi: https://doi.org/10.1136/annrheumdis-2020-217646 Epub 2020 Sep 22. (IF 16.102)
  • Giacomelli R, Afeltra A, Bartoloni E, Berardicurti O, Bombardieri M, Bortoluzzi A, Carubbi F, Caso F, Cervera R, Ciccia F, Cipriani P, Coloma-Bazán E, Conti F, Costa L, D'Angelo S, Distler O, Feist E, Foulquier N, Gabini M, Gerber V, Gerli R, Grembiale RD, Guggino G, Hoxha A, Iagnocco A, Jordan S, Kahaleh B, Lauper K, Liakouli V, Lubrano E, Margiotta D, Naty S, Navarini L, Perosa F, Perricone C, Perricone R, Prete M, Pers JO, Pitzalis C, Priori R, Rivellese F, Ruffatti A, Ruscitti P, Scarpa R, Shoenfeld Y, Triolo G, Tzioufas A. The growing role of precision medicine for the treatment of autoimmune diseases; results of a systematic review of literature and Experts' Consensus. Autoimmun Rev. 2021 Feb;20(2):102738. doi: https://doi.org/10.1016/j.autrev.2020.102738
  • Rivellese F*, Rossi FW*, Giorli G, Napolitano F, de Paulis A, Pitzalis C. Persistence of mast cell-positive synovitis in early 1 rheumatoid arthritis following treatment with conventional synthetic Disease Modifying Anti-Rheumatic Drugs. Front. Pharmacol., 14 July 2020 | https://doi.org/10.3389/fphar.2020.01051
  • Rossi FW*, Rivellese F*, Napolitano F, Mosella F, Selleri C, Montuori N, de Paulis A. Effects of Polyurethane Foam Dressings as an Add-on Therapy in the Management of Digital Ulcers in Scleroderma Patients. *co-first authors. Transl Med UniSa. 2020 May 31;22:10-14. eCollection 2020 May.PMID: 32523901  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265916/
  • Rivellese F, Pontarini E, Pitzalis C. Tertiary Lymphoid Organs in Rheumatoid Arthritis. Curr Top Microbiol Immunol. 2020 Jun 2. doi: 10.1007/82_2020_216
  • Nerviani A, Di Cicco M, Mahto A, Lliso-Ribera G, Rivellese F, Thorborn G, Hands R, Bellan M, Mauro D, Boutet MA, Giorli G, Lewis M, Kelly S, Bombardieri M, Humby F, Pitzalis C. A Pauci-Immune Synovial Pathotype Predicts Inadequate Response to TNFα-Blockade in Rheumatoid Arthritis Patients. Front Immunol. 2020 May 5;11:845. doi: https://doi.org/10.3389/fimmu.2020.00845
  • Lucchesi D, Coleby R, Pontarini E, Prediletto E, Rivellese F, Hill DG, Derrac Soria A, Jones SA, Humphreys IR, Sutcliffe N, Tappuni AR, Pitzalis C, Jones GW, Bombardieri M. Impaired IL-27 Mediated Control of CD4+ T Cell Function Impacts on Ectopic Lymphoid Structure Formation in Patients with Sjögren's Syndrome. Arthritis Rheumatol. 2020 Apr 20. doi: 10.1002/art.41289
  • Rivellese F, Prediletto E. ACE2 at the centre of COVID-19 from paucisymptomatic infections to severe pneumonia. Autoimmun Rev. 2020 Jun;19(6):102536. doi: 10.1016/j.autrev.2020.102536
  • Rivellese F, Humby F, Bugatti S, Fossati-Jimack L, Rizvi H, Lucchesi D, Lliso-Ribera G, Nerviani A, Hands RE, Giorli G, Frias B, Thornborn G, Jaworska E, John C, Goldmann K, Lewis MJ, Manzo A, Bombardieri M, Pitzalis C; PEAC- R4RA investigators. B cell synovitis and clinical phenotypes in rheumatoid arthritis: relationship to disease stages and drug exposure. Arthritis Rheumatol. 2019 Nov 29.  https://doi.org/10.1002/art.41184
  • LLiso-Ribera G, Humby F, Nerviani A, Mauro D, Rivellese F, Kelly S, Hands R, Bene F, Ramamoorthi N, Hackney J, Cauli A, Choy E, Filer A, Taylor P, McInness I, Townsend M, Pitzalis C.
  • Synovial tissue signatures enhance clinical classification and prognostic/treatment response algorithms in early inflammatory arthritis and predict requirement for subsequent biologic therapy: results from the Pathobiology of Early Arthritis Cohort (PEAC). Ann Rheum Dis. 2019 Dec;78(12):1642-1652. https://doi.org/10.1136/annrheumdis-2019-215751
  • Lewis MJ, Barnes MR, Blighe K, Goldmann K, Rana S, Hackney JA, Ramamoorthi N, John CR, Watson DS, Kummerfeld SK, Hands R, Riahi S, Rocher-Ros V, Rivellese F, Humby F, Kelly S, Bombardieri M, Ng N, DiCicco M, van der Heijde D, Landewé R, van der Helm-van Mil A, Cauli A, McInnes IB, Buckley CD, Choy E, Taylor PC, Townsend MJ, Pitzalis C. Molecular Portraits of Early Rheumatoid Arthritis Identify Clinical and Treatment Response Phenotypes. Cell Rep. 2019 Aug 27;28(9):2455-2470.e5.  https://doi.org/10.1016/j.celrep.2019.07.091
  • Rivellese F, Rossi FW, Galdiero MR, Pitzalis C, de Paulis A. Mast Cells in Early Rheumatoid Arthritis. Int J Mol Sci. 2019 Apr 25;20(8). pii: E2040.  https://doi.org/10.3390/ijms20082040
  • Rivellese F, Mauro D, Nerviani A, Pagani S, Fossati-Jimack L, Messemaker T, Kurreeman F, Toes R, Ramming A, Rauber S, Schett G, Jones G, Jones S, Rossi FW, de Paulis A, Marone G, El Shikh M, Humby F, Pitzalis C. Mast cells in early rheumatoid arthritis associate with synovial lymphoid aggregates and support B-cell autoantibody production. Ann Rheum Dis. 2018 Dec;77(12):1773-1781https://doi.org/10.1136/annrheumdis-2018-213418
  • Rivellese F, Lobasso A, Barbieri L, Liccardo B, De Paulis A, Rossi FW. Novel therapeutic approaches in Rheumatoid Arthritis: Role of Janus Kinases Inhibitors. Curr Med Chem. 2018 Feb 9.  https://doi.org/10.2174/0929867325666180209145243 (IF 4.184).
  • Rauber S, Luber M, Weber S, Maul L, Soare A, Wohlfahrt T, Lin NY, Dietel K, Bozec A, Herrmann M, Kaplan MH, Weigmann B, Zaiss MM, Fearon U, Veale DJ, Cañete JD, Distler O, Rivellese F, Pitzalis C, Neurath MF, McKenzie ANJ, Wirtz S, Schett G, Distler JHW, Ramming A. Resolution of inflammation by interleukin-9-producing type 2 innate lymphoid cells. Nat Med. 2017 Aug;23(8):938-944. https://doi.org/10.1038/nm.4373 (IF 36.130)
  • Rivellese F, Nerviani A, Rossi FW, Marone G, Matucci-Cerinic M, de Paulis A, Pitzalis C. Mast cells in rheumatoid arthritis: friends or foes? Autoimmun Rev. 2017 Jun;16(6):557-563.   https://doi.org/10.1016/j.autrev.2017.04.001(IF  7.767)
  • Llibre A, López-Macías C, Marafioti T, Mehta H, Partridge A, Kanzig C, Rivellese F, Galson JD, Walker LJ, Milne P, Phillips RE, Kelly DF, Freeman GJ, El Shikh ME, Klenerman P, Willberg CB.  LLT1 and CD161 Expression in Human Germinal Centers Promotes B Cell Activation and CXCR4 Downregulation. J Immunol. 2016 Mar 1;196(5):2085-94. https://doi.org/10.4049/jimmunol.1502462
  • Rivellese F, de Paulis A, Marone G, Pitzalis C, Toes RE. Reply to: Serum levels of tryptase suggest that mast cells might play an anti-inflammatory functions in Rheumatoid Arthritis. Arthritis Rheumatol.  Arthritis Rheumatol. 2016 Mar;68(3):769-70. https://doi.org/10.1002/art.39505
  • Rivellese F, Suurmond J, Habets K, Dorjée AL, Ramamoorthi N, Townsend MJ, de Paulis A, Marone G, Huizinga TW, Pitzalis C, Toes RE. Ability of Interleukin-33- and Immune Complex-Triggered Activation of Human Mast Cells to Down-Regulate Monocyte-Mediated Immune Responses. Arthritis Rheumatol. 2015 Sep;67(9):2343-53.  https://doi.org/10.1002/art.39192
  • Rivellese F, Suurmond J, de Paulis A, Marone G, Huizinga TW, Toes RE. IgE and IL-33-mediated triggering of human basophils inhibits TLR4-induced monocyte activation. Eur J Immunol. 2014 Oct;44(10):3045-55.  https://doi.org/10.1002/eji.201444731
  • Suurmond J, Rivellese F, Dorjée AL, Bakker AM, Rombouts YJ, Rispens T, Wolbink G, Zaldumbide A, Hoeben RC, Huizinga TW, Toes RE. Toll-like receptor triggering augments activation of human mast cells by anti-citrullinated protein antibodies. Ann Rheum Dis. 2015 Oct;74(10):1915-23.  https://doi.org/10.1136/annrheumdis-2014-205562

Sponsors

Collaborators

Internal
Dr Myles LewisProfessor Michael BarnesDr Cankut CubukKatriona GoldmannElisabetta Sciacca (Centre for Translational Bioinformatics)
Giovanni Giorli (Biostatistician)
Alessandra Nerviani (Clinical Lecturer)

External
Professor Anne Barton (University of Manchester)
Professor Paul McKeigue and Dr Athina Spiliopoulou (University of Edinburgh) Professor Tom Huizinga and Professor Rene Toes (Leiden University)
Dr Andreas Ramming (Erlangen University)
Professor Amato de Paulis and Professor Francesca W Rossi (University of Naples Federico II) 
STRAP and R4RA Investigators and Recruiting Centres
3TR partners