Líneas de investigación

• Antibody–Innate Immune Interactions in Autoimmune Neurological Disorders

  The group investigates the immune mechanisms underlying autoimmune neurological disorders mediated by antibodies against neuronal and glial surface antigens, including autoimmune encephalitis and demyelinating diseases. Our previous work has contributed to the clinical and immunological characterization of these disorders, defining humoral immune signatures that track with disease phenotype, activity, and outcome across conditions such as NMDA receptor, AMPAR, CASPR2 encephalitis and MOG antibody–associated disease. These studies identified compartment-specific antibody features, including Fc glycosylation profiles, that associate with etiology, age, disease activity, and functional recovery. Building on these findings, current research addresses why many patients experience incomplete or prolonged recovery despite immunotherapy. A central objective is to define how Fc-dependent engagement of innate immune pathways, including microglia-mediated mechanisms, contributes to synaptic dysfunction, neuronal injury, and long-term neurological impairment. By integrating systems-level antibody profiling with in vitro and animal models, this work aims to establish mechanistic links between antibody effector functions and tissue damage, identify biomarkers of outcome, and uncover therapeutic targets to improve recovery across autoimmune neurological disorders.

• Viral Triggers of Post-Infectious Brain Autoimmunity

  This research axis investigates how viral infections precipitate antibody-mediated autoimmune neurological disorders, using herpes simplex virus type 1 (HSV1) encephalitis as a model of post-infectious brain autoimmunity. Recent work from the group has shown that qualitative features of the HSV1-specific antibody response, rather than antibody titers alone, associate with disease severity and predict the development of post-herpetic autoimmune encephalitis. In particular, compartment-specific antibody effector functions in cerebrospinal fluid correlate with neuronal injury and clinical outcome, while distinct antiviral antibody profiles are associated with protection in peripheral infection. Ongoing studies aim to define how Fc-dependent innate immune mechanisms regulate viral control, central nervous system invasion, and antibody-mediated neuronal damage during acute infection, and how these processes promote the emergence of pathogenic neuronal autoantibodies. By integrating systems-level antibody profiling and human neuronal infection models, this work seeks to identify immune determinants of susceptibility, protection, and long-term neurological sequelae following viral encephalitis.

• Antibody Correlates Of Protection In Infectious Brain Disorders To Guide Next-Generation Vaccines

  This research axis focuses on identifying antibody correlates of protection and pathogenicity in neuroinfectious and neuroinflammatory disorders. Previous work has shown that qualitative features of antibody responses, shaped by immunological imprinting and tissue compartmentalization, critically influence neurological outcomes across infections. These studies demonstrated that pre-existing coronavirus immunity can skew SARS-CoV-2–specific antibody responses and contribute to persistent neurological sequelae, that Mycobacterium tuberculosis elicits distinct antibody programs in pulmonary versus brain infection, and that antibodies are functionally compartmentalized within the central nervous system during chronic HIV infection. Building on these findings, ongoing work examines how antibody effector functions and innate immune engagement regulate pathogen control, neuroinflammation, and long-term neurological dysfunction. This work provides a framework to guide the development of next-generation vaccines and immune-based therapies for infections affecting the nervous system.