Autoimmunity and Neurosciences

Group leader

Principal Investigator

Team members

Alexandre Mendes, MD, PhD

Integrated PhD researcher

    Ana Martins da Silva, MD, PhD

    Integrated PhD researcher

      António Marinho, MD, PhD

      Integrated PhD researcher

        António Martins da Silva, MD, PhD

        Integrated PhD researcher

          Bárbara Leal, PhD

          Integrated PhD researcher

            Betânia Ferreira, MD

            PhD Student

              Carlos Vasconcelos, MD, PhD

              Integrated PhD researcher

                Ernestina Santos, MD, PhD

                Integrated PhD researcher

                  Henrique Reguengo, MSc

                  PhD Student

                    Isabel Almeida, MD, PhD

                    Integrated PhD researcher

                      Ivone Silva, MD, PhD

                      Integrated PhD researcher

                        João Araújo Correia, MD, PhD

                        Clinical researcher

                        Director of the Internal Medicine Service - CHUP

                          João Chaves, MD

                          Integrated PhD researcher

                            José Carlos Oliveira, MD, PhD

                            Laboratory researcher

                            Head of Clinical Chemistry at CHUP

                              Manuel Melo Pires, MD, PhD

                              Integrated PhD researcher

                                Paulo Barbosa, MD, PhD

                                Clinical researcher

                                President of the Administration Council of CHUP

                                  Paulo Pinho e Costa, MD, PhD

                                  Integrated PhD researcher

                                    Raquel Faria, MD

                                    PhD Student

                                      Tiago Torres, MD, PhD

                                      Integrated PhD researcher

                                        Introduction

                                        The AI&NS is a multidisciplinary research group that gathers professionals from different scientific areas and disciplines, such as clinical immunology, immunogenetics, neurology, neurophysiology, neuropsychology, neuroradiology, neurosurgery, and pathology.

                                        This group was studying the heterogeneity of complex inflammation-associated diseases to uncover new biomarkers for disease susceptibility, progression, and treatment response. They have been gathering molecular and clinical data associated with disease physiopathology and progression of such diseases studying large cohorts of patients. The aim was to contribute to a better classification of these diseases and subsequent earlier and more effective treatments.

                                        The AI&NS group was able to show the contribution of genetic – HLA, vitamin D receptors – and epigenetic – microRNA’s – factors with clinical subgroups, severity and outcomes. This has been explored in Systemic Lupus Erythematosus (SLE), Multiple Sclerosis (MS), Behçet’s Disease (BD), Sleep (Hyersomnolence) Disorders, and Epilepsy (Mesial Temporal Lobe Epilepsy – MTLE).

                                        Differently from “Classical” Autoimmune/Inflammatory Diseases, Sleep Disorders cursing with daytime hypersomnolence, namely narcolepsy type 1 (N1), type 2 (N2) and Idiopathic Hypersomnia (IH) are, many times, difficult to be distinguished on the course of the disease. They demonstrated that genetic identification of different HLA alleles was able to help on such distinction.

                                        Other, “Non-Classical” Autoimmune/Inflammatory Disease is Mesial Temporal Lobe Epilepsy in which its resistance to treatment has been associated to CNS inflammation. The AI&NS group demonstrated that purinergic –inflammatory axis is dysregulated in this syndrome contributing to seizure propagation and to a poor response to pharmacological treatment.


                                        Aims

                                        The primary research goals are:

                                        • To identify prognostic and predictive biomarkers of autoimmune and neurodegenerative diseases, with an emphasis on genetic, immunological and neurobehavioral factors, through the investigation of common etiological and pathophysiological mechanisms.
                                        • To provide new markers of disease risk and disease progression, in order to improve preventive care and therapeutic strategies.
                                        • To identify predictors of clinical variability and treatment outcomes in Autoimmune, Neurodegenerative and Autoimmune/ Neurodegenerative diseases.

                                        Highlighted publications

                                        1. Langefeld CD, Ainsworth HC, Cunninghame Graham DS, Kelly JA, Comeau ME, Marion MC, Howard TD, Ramos PS, Croker JA, Morris DL, Sandling JK, Almlöf JC, Acevedo-Vásquez EM, Alarcón GS, Babini AM, Baca V, Bengtsson AA, Berbotto GA, Bijl M, Brown EE, Brunner HI, Cardiel MH, Catoggio L, Cervera R, Cucho-Venegas JM, Dahlqvist SR, D’Alfonso S, Da Silva BM, de la Rúa Figueroa I, Doria A, Edberg JC, Endreffy E, Esquivel-Valerio JA, Fortin PR, Freedman BI, Frostegård J, García MA, de la Torre IG, Gilkeson GS, Gladman DD, Gunnarsson I, Guthridge JM, Huggins JL, James JA, Kallenberg CGM, Kamen DL, Karp DR, Kaufman KM, Kottyan LC, Kovács L, Laustrup H, Lauwerys BR, Li QZ, Maradiaga-Ceceña MA, Martín J, McCune JM, McWilliams DR, Merrill JT, Miranda P, Moctezuma JF, Nath SK, Niewold TB, Orozco L, Ortego-Centeno N, Petri M, Pineau CA, Pons-Estel BA, Pope J, Raj P, Ramsey-Goldman R, Reveille JD, Russell LP, Sabio JM, Aguilar-Salinas CA, Scherbarth HR, Scorza R, Seldin MF, Sjöwall C, Svenungsson E, Thompson SD, Toloza SMA, Truedsson L, Tusié-Luna T, Vasconcelos C, Vilá LM, Wallace DJ, Weisman MH, Wither JE, Bhangale T, Oksenberg JR, Rioux JD, Gregersen PK, Syvänen AC, Rönnblom L, Criswell LA, Jacob CO, Sivils KL, Tsao BP, Schanberg LE, Behrens TW, Silverman ED, Alarcón-Riquelme ME, Kimberly RP, Harley JB, Wakeland EK, Graham RR, Gaffney PM, Vyse TJ. Transancestral mapping and genetic load in systemic lupus erythematosus. Nat Commun. 2017 Jul 17;8:16021. doi: 10.1038/ncomms16021
                                        2. Nour MM, Nakashima I, Coutinho E, Woodhall M, Sousa F, Revis J, Takai Y, George J, Kitley J, Santos ME, Nour JM, Cheng F, Kuroda H, Misu T, Martins-da-Silva A, DeLuca GC, Vincent A, Palace J, Waters P, Fujihara K, Leite MI. Pregnancy outcomes in Aquaporin 4- positive neuromyelitis optica spectrum disorder; Neurology. 2016 Jan 5;86(1):79-87. doi: 10.1212/WNL.0000000000002208
                                        3. Kasperaviciute D, Catarino CB, Matarin M, Leu C, Novy J, Tostevin A, Leal B, Hessel EV, Hallmann K, Hildebrand MS, Dahl HH, Ryten M, Trabzuni D, Ramasamy A, Alhusaini S, Doherty CP, Dorn T, Hansen J, Krämer G, Steinhoff BJ, Zumsteg D, Duncan S, Kälviäinen RK, Eriksson KJ, Kantanen AM, Pandolfo M, Gruber-Sedlmayr U, Schlachter K, Reinthaler EM, Stogmann E, Zimprich F, Théâtre E, Smith C, O’Brien TJ, Meng Tan K, Petrovski S, Robbiano A, Paravidino R, Zara F, Striano P, Sperling MR, Buono RJ, Hakonarson H, Chaves J, Costa PP, Silva BM, da Silva AM, de Graan PN, Koeleman BP, Becker A, Schoch S, von Lehe M, Reif PS, Rosenow F, Becker F, Weber Y, Lerche H, Rössler K, Buchfelder M, Hamer HM, Kobow K, Coras R, Blumcke I, Scheffer IE, Berkovic SF, Weale ME; UK Brain Expression Consortium, Delanty N, Depondt C, Cavalleri GL, Kunz WS, Sisodiya SM. Epilepsy, hippocampal sclerosis and febrile seizures linked by common genetic variation around SCN1A. Brain. 2013 Oct;136(Pt 10):3140-50. doi: 10.1093/brain/awt233

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