Immune response and vascular disease

jose delgado alves

José Alves

Principal Investigator



Campus Sant'Ana
Pólo de Investigação, NMS, UNL
Rua Câmara Pestana, nº 6
Lab 3.16
1150-082 Lisboa, Portugal

Phone: (+351) 218 803 038 (ext 22492)
Lab Ext: 26012
Fax: (+351) 351 218 803 028
E-mail: jose.alves(at)

Main interests

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.

Prizes and Grants

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)


- Maratona da Saúde (RTP) – March 2018
- Jornal Hospital Público – May 2018
- Entrevista sobre lupus (RTP) – 2016
- Live Medicina Interna – 2015 (p.52)


- Characterization of anti-HDL (aHDL) antibodies: identification of their biologic activity and clinical relevance - iNOVA4Health

- Humoral response towards HDL and vascular risk in patients with Psoriasis – Pfizer

- Familial Risk in Raynaud´s Disease, Systemic Sclerosis and Diabetes Mellitus– the role of vascular memory - Actelion International

- HDL in regulation of T cell activation.- Fundação Amadeu Dias

- Role of Dll-4 on the endothelial dysfunction in systemic sclerosis- Bolsa de Estudo em Autoimunidade NEDAI da SPMI

- Importance of Nailfold Capillaroscopy in Raynaud’s Phenomenon and other Immune-Mediated Vascular Diseases, Actelion International

- Anti-apolipoprotein A-I antibodies in the pathogenesis of Alzheimer disease - EXPL/NEU-SCC/0186/2012 and Fundação Amadeu Dias

- Importance of antibodies anti-IFN-gamma as a new family of autoantibodies. -Several sponsorships

- Neutralizing antibodies in anti-TNF therapy. -Private sponsorships

- Antibodies against the acetylcholine receptor as an indicator for diagnosis and therapy of Myasthenia Gravis. -Several sponsorships

- Clinical trial EXPLORE: “Exploratory, double blind placebo controlled, randomized, single cross-over study to evaluate the potential anti-oxidant action of Niaspan” -Merck Serono S.A.

  • Amengual O, Forastiero R, Sugiura-Ogasawara M, Otomo K, Oku K, Favas C, Delgado Alves J, Žigon P, Ambrožič A, Tomšič M, Ruiz-Arruza I, Ruiz-Irastorza G, Bertolaccini ML, Norman GL, Shums Z, Arai J, Murashima A, Tebo AE, Gerosa M, Meroni PL, Rodriguez-Pintó I, Cervera R, Swadzba J, Musial J, Atsumi T. Evaluation of phosphatidylserine-dependent antiprothrombin antibody testing for the diagnosis of antiphospholipid syndrome: results of an international multicentre study. Lupus. 2017 Mar;26(3):266-276. doi: 10.1177/0961203316660203
  • Ames PR, Margaglione M. Incidental splanchnic vein thrombosis: preliminary registry data. Lancet Haematol 2016; 3(6):e256-7.
  • Sokoll, K. B., Batuca, J., Lopez, L. R., Hensor, E., Emery, P., Delgado Alves, J., & Ames, P. R. J. Effects of Atorvastatin on Atherosclerosis and Atherogenesis in Systemic Lupus Erythematosus: A Pilot Study. ISRN Immunology 2014; Article ID 295239, 7 p.
  • 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
  • Ames PR, Batuca JR, Muncy IJ, De La Torre IG, Pascoe-Gonzales S, Guyer K, Matsuura E, Lopez LR. Aspirin insensitive thromboxane generation is associated with oxidatve stress in type 2 diabetes mellitus. Thromb Res 2012; 130:350-4.
  • Alves JD, Marinho A, Serra MJ. Tocilizumab: is there life beyond anti-TNF blockade? Int J Clin Pract 2011; 65(4):508-13.
  • Neves M, Alves JD. Factors implicated in the generation and persistence of long-lived plasma cell-mediated autoimmunity. Autoimmun Rev 2011; 10(7):375-82.
  • Ferreira I, Neves M, Alves JD. Atherosclerosis risk in antiphospholipid syndrome. Int J Clin Rheum 2011; 6(5): 583-593.
  • Ames PRJ, Ortiz-Cadenas A, Garcia-de la Torre I, Nava A, Oregon-Miranda A, Batuca JR, Kojima K, Lopez LR, Matsuura E. Rosuvastatin treatment is associated with a decrease of serum oxidised low-density lipoprotein/beta2-glycoprotein I complex concentration in type 2 diabetes. Br J Diabetes Vasc Dis 2010; 10: 292-299.
  • Ames PR, Batuca JR, Ciampa A, Iannaccone L, Delgado Alves J. Clinical relevance of nitric oxide metabolites and nitrative stress in thrombotic primary antiphospholipid syndrome. J Rheumatol 2010; 37(12):2523-30.
  • Amaral M, Favas C, Delgado Alves J. Persistency of low levels of anticardiolipin and anti-beta2 glycoprotein1 in thrombosis. Eur J Intern Med 2010; 21(2):101-3.
  • Ames PR, Matsuura E, Batuca JR, Ciampa A, Lopez LL, Ferrara F, Iannaccone L and Delgado Alves J. High-density lipoprotein inversely relates to its specific auntoantibody favoring oxidation in thrombotic primary antiphospholipid syndrome. Lupus 2010; 19(6):711-6.
  • Ames PR, Margaglione M, Mackie S, Alves JD. Eosinophilia and thrombophilia in churg strauss syndrome: a clinical and pathogenetic overview. Clin Appl Thromb Hemost 2009; 16(6):628-36.
  • Charakida M, Besler C, Batuca JR, Sangle S, Marques S, Sousa M, Wang G, Tousoulis D, Delgado Alves J, Mackworth-Young C, Hughes G, D’Cruz D, Luscher T, Landmesser U and Deanfield JE. (2009) Vascular dysfunction in primary antiphospholipid syndrome; role of dysfunctional high density lipoprotein. JAMA 302(11):1210-1217.
  • Ames PR, Margarita A, Alves JD. Antiphospholipid antibodies and atherosclerosis: insights from systemic lupus erythematosus and primary antiphospholipid syndrome. Clin Rev Allergy Immunol 2009; 7(1):29-35.
  • Batuca JR and Delgado Alves J. C-reactive protein in systemic lupus erythematosus. Autoimmunity 2009. 42(4):282-5.
  • Batuca JR, Amaral MC and Delgado Alves J. Humoral Mechanismof Atherogenesis. Ann N Y Acad Sci 2009; 1173:401-408.
  • Batuca JR, Ames PR, Amaral MC, Favas C, Isenberg DA and Delgado Alves J. Anti-atherogenic and anti-inflammatory properties of high-density lipoprotein are affected by specific antibodies in systemic lupus erythematosus. Rheumatology (Oxford) 2009; 48(1):26-31.
  • Amaral MC, Alves JD. Pathogenesis of multi-organic failure in autoimmune diseases.Autoimmun Rev 2009; 8(6):525-8.
  • Pereira SA, Batuca JR, Caixas U, Branco T, Delgado-Alves J, Germano I, Lampreia F and Monteiro EC. Effect of efavirenz on high-density lipoprotein antioxidant properties in HIV-infected patients. Br J Clin Pharmacol 2009; 68(6):891-7.
  • Ames PR, Antinolfi I, Ciampa A, Batuca JR, Scenna G, Lopez LR, Delgado Alves J, Iannaccone L and Matsuura E. Primary antiphospholipid syndrome: a low-grade auto-inflammatory disease? Rheumatology (Oxford) 2008; 47(12):1832-7.
  • Alves JD, Steinhagen-Thiessen E, Darioli R, Hostalek U, Vogt A. Influence of the timing of low-dose aspirin on tolerability of prolonged-release nicotinic acid in patients at elevated cardiovascular risk. Curr Med Res Opin 2008; 24(10):2815-20.
  • Ehrenstein MR, Alves JD. Antibodies and other biomarkers - pathological consequences (2). Lupus 2008; 17(3):256-8.
  • Batuca JR, Ames PRJ, Isenberg DA, Delgado Alves J. Antibodies toward High-Density Lipoprotein Components Inhibit Paraoxonase Activity in Patients with Systemic Lupus Erythematosus. Ann N Y Acad Sci 2007; 1108 (1), 137–146.
  • Margarita A, Batuca J, Scenna G, Delgado Alves J., Lopez L, Iannaccone L, Matsuura E, Ames PRJ. Subclinical Atherosclerosis in Primary Antiphospholipid Syndrome. Ann N Y Acad Sci 2007; 1108 (1), 475–480.
  • Ames PR, Delgado Alves J, Lopez LR, Gentile F, Margarita A, Pizzella L, Batuca JR, Scenna G, Brancaccio V and Matsuura E. Antibodies against beta2-glycoprotein I complexed with an oxidised lipoprotein relate to intima thickening of carotid arteries in primary antiphospholipid syndrome. Clin Dev Immunol 2006; 13(1):1-9.
  • Alves JD, Clapp BR, Stidwill R, Chen PP, Hingorani AD, Singer M, Isenberg DA. Human monoclonal IgG anticardiolipin antibodies induce nitric oxide synthase expression. Atherosclerosis 2006; 185(2):246-53.
  • Ames PR, Iannaccone L, Alves JD, Margarita A, Lopez LR, Brancaccio V. Factor XIII in primary antiphospholipid syndrome.J Rheumatol 2005; 32(6):1058-62.
  • Delgado Alves J, Mason LJ, Ames PR, Chen PP, Rauch J, Levine JS, Subang R, Isenberg DA. Antiphospholipid antibodies are associated with enhanced oxidative stress, decreased plasma nitric oxide and paraoxonase activity in an experimental mouse model. Rheumatology (Oxford) 2005; 44(10):1238-44.
  • Delgado Alves J, Radway-Bright EL, Lee S, Grima B, Hothersall J, Ravirajan CT, Isenberg DA. Antiphospholipid antibodies are induced by in vitro fertilization and correlate with paraoxonase activity and total antioxidant capacity of plasma in infertile women. Lupus 2005; 14(5):373-80.
  • Delgado Alves J, Inanc M, Diz-Kucukkaya R, Grima B, Soromenho F, Isenberg DA. Thrombotic risk in patients submitted to splenectomy for systemic lupus erythematosus and antiphospholipid antibody syndrome-related thrombocytopenia. Eur J Intern Med 2004; 15(3):162-167.
  • Shoenfeld Y, Lev S, Blatt I, Blank M, Font J, von Landenberg P, Lev N, Zaech J, Cervera R, Piette JC, Khamashta MA, Bertolaccini ML, Hughes GR, Youinou P, Meroni PL, Pengo V, Alves JD, Tincani A, Szegedi G, Lakos G, Sturfelt G, Jönsen A, Koike T, Sanmarco M, Ruffatti A, Ulcova-Gallova Z, Praprotnik S, Rozman B, Lorber M, Chapman J, van-Breda-Vriezman PJ, Damoiseaux J. Features associated with epilepsy in the antiphospholipid syndrome. J Rheumatol 2004; 31(7):1344-8.
  • Shoenfeld Y, Krause I, Kvapil F, Sulkes J, Lev S, von Landenberg P, Font J, Zaech J, Cervera R, Piette JC, Boffa MC, Khamashta MA, Bertolaccini ML, Hughes GR, Youinou P, Meroni PL, Pengo V, Alves JD, Tincani A, Szegedi G, Lakos G, Sturfelt G, Jönsen A, Koike T, Sanmarco M, Ruffatti A, Ulcova-Gallova Z, Praprotnik S, Rozman B, Lorber M, Vriezman VB, Blank M. Prevalence and clinical correlations of antibodies against six beta2-glycoprotein-I-related peptides in the antiphospholipid syndrome. J Clin Immunol 2003; 23(5):377-83.
  • Alves JD, Grima B. Oxidative stress in systemic lupus erythematosus and antiphospholipid syndrome: a gateway to atherosclerosis. Curr Rheumatol Rep 2003; 5(5):383-90.
  • Alves JD, Ames PR. Atherosclerosis, oxidative stress and auto-antibodies in systemic lupus erythematosus and primary antiphospholipid syndrome. Immunobiology 2003; 207(1):23-8.
  • Delgado Alves J, Kumar S, Isenberg DA. Cross-reactivity between anti-cardiolipin, anti-high-density lipoprotein and anti-apolipoprotein A-I IgG antibodies in patients with systemic lupus erythematosus and primary antiphospholipid syndrome. Rheumatology (Oxford) 2003; 42(7):893-9.
  • Delgado Alves J, Ames PR, Donohue S, Stanyer L, Nourooz-Zadeh J, Ravirajan C, Isenberg DA. Antibodies to high-density lipoprotein and beta2-glycoprotein I are inversely correlated with paraoxonase activity in systemic lupus erythematosus and primary antiphospholipid syndrome. Arthritis Rheum 2002; 46(10):2686-94.
  • Ames PR, Margarita A, Delgado Alves J, Tommasino C, Iannaccone L, Brancaccio V. Anticardiolipin antibody titre and plasma homocysteine level independently predict intima media thickness of carotid arteries in subjects with idiopathic antiphospholipid antibodies. Lupus 2002; 11(4):208-14.



- 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

Team photos

grupo irvd

Team Jose Alves