IVIg effects on regulatory B cells in patients with neuroimmune diseases

Intravenous immunoglobulins (IVIg) are an efficient anti-inflammatory and immunomodulatory treatment used in a number of neurological diseases, among others, inflammatory neuropathies and worsening myasthenia gravis. The finding of serum antibodies in patients suffering from these IVIG-responding conditions provides these pathologies with one remarkable common feature: effector B lymphocytes seem to be somehow involved in their pathogenesis, hence our interest in characterizing B cells upon IVIg treatment.
While widely and successfully used in clinical practice IVIg's mechanism(s) remain uncertain. Studies involving IVIg effects on B-cells have been conducted using in vitro experiments and animal models providing relevant yet partial data. The effect of IVIg therapy on B-cells in general and, more specifically, on regulatory B cells (Bregs) in the context of neuroimmune diseases is currently poorly understood.

Bregs are a rare subset of B type lymphocytes that suppress immunopathology acting upon several target cells in the immune system. Impaired Breg yields have been described in a plethora of autoimmune conditions, such as multiple sclerosis, rheumatoid arthritis or type 1 diabetes. To further highlight the contribution of this cell subset to immunomodulation, its depletion has been described to exacerbate autoimmunity in several murine models.

With our project we aim to uncover potentially relevant mechanisms of action of IVIg, as well as to characterize the role of Bregs in the pathogenesis of neuroinmmune diseases. Granted the validity of our hypothesis, which have met encouraging preliminary results, this study would provide invaluable information in terms of prognostic and responsiveness to treatment biomarkers. Additionally, molecular arrays might provide insight into new IVIg targets. They might also explain the poor response to IVIg treatment that some subgroups of patients experience.

Curriculum Vitae

Luis Querol (Valencia, 1980) graduated in Medicine at University of Oviedo. He completed his residency in Neurology at the Hospital de la Santa Creu i Sant Pau in Barcelona.

In 2009 he was awarded a Rio- Hortega contract in the Neuroimmunology field in the group of Dr. Isabel Illa, where he developed his thesis on the role of autoantibodies in immune-mediated neuropathies.

During his last year of Rio Hortega contract, in 2012, he worked as a research associate in the Department of Neurology at Yale University (USA) in the group of Dr Kevin O'Connor, where he conducted projects related autoantibodies in multiple sclerosis and myasthenia gravis.

Led by Dr. Illa, he completed his Doctorate in Medicine at the Autonomous University of Barcelona in 2013, thanks to studies that identified antibodies with clinical utility in autoimmune neuropathies. In particular he described the anti-contactin antibodies in a characteristic subgroup of patients with CIDP, the first biomarker detected in CIDP with clinical utility.

After his US rotation he continued to work at the Neuromuscular Diseases Unit of the Hospital de la Santa Creu i Sant Pau, where he combines clinical care, with special interest in autoimmune disease of the peripheral nervous system, with the laboratory and translational research in the field of autoantibodies and immune-mediated neuropathies.

Luis Querol has received th Best Young Clinical Investigator CIBERNED 2013 award and the 2014 PK Thomas prize for best presentation in the field of neuropathies of the European Federation of Neurological Societies, both for his work with autoantibodies in CIDP

Academic Training

• Graduate in Medicine (University of Oviedo), 2004
• Doctor in Medicine ( Autonomous University of Barcelona), 2013

Grants and Awards

• Rio- Hortega Research Contract (Instituto de Salud Carlos III), 2009-2012
• Juan Rodes Contract Research (Instituto de Salud Carlos III), 2013-
• Award for Best Young Clinical Investigator CIBERNED, 2013
• PK Thomas Prize, EFNS, 2014

Areas of investigation

• Immunopathogenesis of CIDP, special interest on B cells and antibodies
• Role of B cells and autoantibodies in other neuroimmune diseases