Immune Response and Vascular Disease

Our research focuses mainly on the connection between immunology and vascular disease. We work in a translational science workflow, with a strong interrelationship between basic science and clinical medicine. 

Adaptive and innate immune responses, as well as inflammation, are frequent phenomena throughout life and are cornerstones in the pathophysiology of autoimmune diseases, diabetes mellitus, atherosclerosis or neurodegenerative diseases. The interrelationship between these entities (immune response, inflammation, endothelial dysfunction, atherogenesis) is a central interest in our research, framing these mechanisms in multiple pathological contexts, such as cardiovascular diseases (eg. atherosclerosis, acute myocardial infarction/stroke, heart failure), immune-mediated diseases (eg. lupus, rheumatoid arthritis, systemic sclerosis), or neurodegeneration (eg. Alzheimer’s disease).

Of the main research areas with active projects, we highlight the following:

  • Characterization of a new family of antibodies against components of lipoproteins, especially against high density lipoproteins (HDL), which can block or disrupt their normal function in maintaining a healthy endothelium. This mechanism could be partially responsible for the increased cardiovascular risk associated with several autoimmune diseases, as in systemic lupus erythematosus, rheumatoid arthritis or psoriasis, but also for atherogenesis sensu lato such as in diabetes mellitus.
  • Interference of HDL particles in T lymphocyte biology, especially in systemic lupus erythematosus, where we study the dynamics of immune synapses in response to HDL and anti-HDL antibodies
  • The role if anti-HDL antibodies in amyloid-beta deposition in Alzheimer’s disease.
  • Microvascular dysfunction and dysangiogenesis, with a particular focus on the Notch signalling system and on the microanatomical changes seen through videocapillaroscopy, in two pathological models: systemic sclerosis and diabetes mellitus.
  • Emergence of neutralizing antibodies against biologic therapies, which results in treatment failure in several diseases.
  • Antibodies against HDL-Cholesterol lipoproteins, autoimmune diseases and cardiovascular disease
  • Antibodies against apolipoprotein A-I in Alzheimer’s disease
  • The role of the Notch signalling pathway in the microvascular dysfunction of systemic sclerosis
  • Vascular memory in Raynaud’s phenomenon and systemic sclerosis
  • Autoimmunity against lipoproteins in type 1 and type 2 diabetes mellitus
  • Endothelial dysfunction and subclinical diastolic dysfunction in systemic lupus erythematosus and systemic sclerosis.
  • Differential serum-plasma VEGF levels in vascular disease
  • Neutralizing antibodies against biologic drugs in autoimmune diseases

Seguro Paula F, Delgado Alves J. The role of the Notch pathway in the pathogenesis of systemic sclerosis: clinical implications. Exp Rev Clin Immunol 2021. doi: 10.1080/1744666X.2021.20003914

Fernandes das Neves M, Batuca J R, Delgado Alves J. The role of high-density lipoprotein in the regulation of the immune response: implications for atherosclerosis and autoimmunity. Immunology 2021; 00:1-11. doi: 10.1111/imm.13348

Fernandes das Neves M, Jury EC, Delgado Alves J. High density lipoprotein influences CD4 T cell proliferation in Systemic Lupus Erythematosus and increases TGF-β1 expression: A potential role in the protection from atherosclerosis and autoimmunity. Lupus. July 2021. doi: 10.1177/09612033211034557

Ribeiro R, Serôdio JF, Amaral MC, Duarte JA, Durão C, Mendes N, Delgado Alves J. Sensorineural Hearing Loss and Systemic Autoimmune Disease: The Experience of a Systemic Immune-Mediated Diseases Unit. Cureus. 2021 Mar 24;13(3):e14075

Serodio JF, Lopes M, Ribeiro R, Trindade M, Favas C, Alves JD. Hepatic fascioliasis as an important differential diagnosis to cholangiocarcinoma. J Travel Med. 2021:taab061. 

Alenquer M, Silva TM, Akpogheneta O, Ferreira F, Vale-Costa S, Medina-Lopes M, Batista F, Garcia AM, Barreto VM, Paulino C, Costa J, Sobral J, Diniz-Costa M, Ladeiro S, Alves JD, Leite RB, Demengeot J, Brito MR,  Amorim MJ. Saliva molecular testing bypassing RNA extraction is suitable for monitoring and diagnosing SARS-CoV-2 infection in children. medRxiv 2021.08.11.21261899; doi:

Oliveira RP, Ribeiro R, Melo L, Grima B, Oliveira S, Alves JD. Connective tissue disease-associated interstitial lung disease. Pulmonology. 2020: S2531-0437(20)30004-0. 

Gonçalves J, Sousa RL, Jacinto MJ, Silva DA, Paula F, Sousa R, Zahedi S, Carvalho J, Cabral MG, Costa M, Branco JC, Canhão H, Alves JD, Rodrigues AM, Soares H. Evaluating SARS-CoV-2 Seroconversion Following Relieve of Confinement Measures. Front Med (Lausanne) 2020;7:603996. doi: 10.3389/fmed.2020.603996. PMID: 33392225; PMCID: PMC7775303.

Paiva-Lopes MJ, Batuca JR, Gouveia S, Alves M, Papoila AL, Delgado Alves J. Antibodies towards high-density lipoprotein components in patients with psoriasis. Arch Dermatol Res 2019.

Ribeiro R, Batista F, Paula FS, Delgado Alves J. Changes in iron metabolism induced by anti-interleukin-6 receptor monoclonal antibody are associated with an increased risk of infection. Pharmaceuticals. 2019;12(3):100. 

Batuca JR, Amaral MC, Favas C, Justino GC, Papoila AL, Ames PRJ, Alves JD. Antibodies against HDL Components in Ischaemic Stroke and Coronary Artery Disease. Thromb Haemost. 2018 Jun;118(6):1088-1100

Caetano J, Paula FS, Amaral MC, Oliveira S, Delgado Alves J. Nailfold Videocapillaroscopy Changes Are Associated with the Presence and Severity of Systemic Sclerosis-Related Interstitial Lung Disease. J Clin Rheumatol. 2018 May 19. doi: 10.1097/RHU.0000000000000815

Batuca JR, Amaral MC, Favas C, Paula FS, Ames PR, Papoila AL, Delgado Alves J. Extended-release niacin increases anti-apolipoprotein A-I antibodies that block the antioxidant effect of high-density lipoprotein-cholesterol: the EXPLORE clinical trial. Br J Clin Pharmacol. 2017 May;83(5):1002-1010

Paula FS, Ferreira I, Amaral MC, Delgado Alves J. Systemic sclerosis-related changes on nailfold videocapillaroscopy in genetic and metabolic myopathies. Rheumatology (Oxford). 2016 Oct;55(10):1911-2

Sokoll KB, Batuca J, Lopez LR, Hensor E, Emery P, Delgado Alves J, Ames PRJ. Effects of Atorvastatin on Atherosclerosis and Atherogenesis in Systemic Lupus Erythematosus: A Pilot Study ISRN Immunology. 2014 Article ID 29523

Paula FS, Alves JD.Non-tumor necrosis factor-based biologic therapies for rheumatoid arthritis: present, future, and insights into pathogenesis. Biologics 2014;8:1-12


2019 – NOVARTIS | Excellence in Fundamental Medical Research, NOVA Medical School (Paula FS, Delgado Alves J)
2018 – Bolsa NEDM/Lilly, Diabetes Mellitus Studies Nucleus (NEDM), Portuguese Society of Internal Medicine (SPMI) (Batista F, Paula FS, Delgado Alves)
2018 – Bolsa Helena Saldanha (Boehringer Ingelheim), Diabetes Mellitus Studies Nucleus (NEDM), Portuguese Society of Internal Medicine (SPMI) (Amaral M, Delgado Alves J)
2018 – Maratona da Saúde, RTP (Neves M, Delgado Alves J)
2016 - Research Grant in Autoimmunity and Rare Diseases, Autoimmune Diseases Studies Nucleus (NEDAI), Portuguese Society of Internal Medicine (SPMI) (Amaral M, Delgado Alves J)
2015 – Fellowship award, FCT (Batuca J)
2015 - Pfizer Award Best Poster Autoimmunity, Autoimmune Diseases Studies Nucleus (NEDAI), Portuguese Society of Internal Medicine (SPMI) (Paula FS, Amaral M, Delgado Alves J)
2013 - Research Grant in Autoimmunity, Autoimmune Diseases Studies Nucleus (NEDAI), Portuguese Society of Internal Medicine (SPMI) (Paula FS, Amaral M, Delgado Alves J)
2013 – FCT Research Grant (Valverde AH)

Internal Medicine Department 4 - Fernando Fonseca Hospital, Amadora, Portugal
Systemic Immune-mediated Diseases Unit – Fernando Fonseca Hospital, Amadora, Portugal
Centre for Molecular Pathogenesis – Retrovirus and Associated infections unit (CPM-URIA), Faculty of Pharmacy – University of Lisbon, Portugal
Centre for Haemostasis and Thrombosis St George’s Healthcare, University of London, United Kingdom
Centre for Rheumatology Research, University College London, United Kingdom
Department of Biochemistry, University of Okayama, Japan
Dipartimento di Medicina e Scienze della Salute, Università del Molise, Italy
Tropical Diseases Unit and Centre of Malaria and Tropical Diseases, IHMT, Portugal
Neo-vascularization Unit, Molecular Medicine Institute, Portugal

Principal Investigator

José Delgado Alves


Filipe Paula
Research Coordinator
Paul Ames
Research Fellow
Joana Batuca
Research Fellow
Catarina Favas
Researcher, MD
Joana Caetano
Researcher, MD
Marisa Neves
Researcher, MD
Frederico Batista
Researcher, MD
Marta Carapeto Amaral
Researcher, MD