RESUMEN
Imlifidase (IdefirixTM), a cysteine protease derived from the immunoglobulin G (IgG)degrading enzyme of Streptococcus (S.) pyogenes is being developed by Hansa Biopharma AB for treatment of transplant rejection and rare IgG-mediated autoimmune conditions. In August 2020, intravenous imlifidase received its first global approval in the EU for desensitization treatment of highly sensitized adult kidney transplant patients with positive crossmatch against an available deceased donor. Imlifidase is currently undergoing clinical evaluation for the prevention of kidney transplant rejection in the USA, Australia, France and Austria, and clinical development is underway for anti-glomerular basement membrane disease, and for Guillain-Barre syndrome in France, the UK and the Netherlands. This article summarizes the milestones in the development of imlifidase leading to this first approval for desensitization treatment of highly sensitized adult kidney transplant patients with positive crossmatch against an available deceased donor.
Asunto(s)
Enfermedad por Anticuerpos Antimembrana Basal Glomerular/tratamiento farmacológico , Proteínas Bacterianas/uso terapéutico , Aprobación de Drogas , Rechazo de Injerto/tratamiento farmacológico , Síndrome de Guillain-Barré/tratamiento farmacológico , Administración Intravenosa , Animales , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/inmunología , Proteínas Bacterianas/farmacología , Ensayos Clínicos Fase I como Asunto , Ensayos Clínicos Fase II como Asunto , Desensibilización Inmunológica/métodos , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Unión Europea , Síndrome de Guillain-Barré/inmunología , Antígenos HLA/inmunología , Humanos , Inmunoglobulina G/inmunología , Inmunoglobulina G/metabolismo , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Enfermedades Raras/tratamiento farmacológico , Enfermedades Raras/inmunologíaRESUMEN
Autoimmune Syndrome Induced by Adjuvant (ASIA) is a definition aimed to describe the common etiological process at the root of five clinical entities sharing similar symptomatology: macrophagic myofasciitis syndrome (MMF), Gulf War Syndrome (GWS), sick building syndrome (SBS), siliconosis, and post vaccination autoimmune phenomena. ASIA illustrates the role of environmental immune stimulating agents, or adjuvants, in the instigation of complex autoimmune reactions among individuals bearing a genetic preponderance for autoimmunity. The value of ASIA lies first in the acknowledgment it provides for patients suffering from these as yet ill-defined medical conditions. Equally important is the spotlight it sheds for further research of these poorly understood conditions sharing a common pathogenesis. In this article we elaborate on the significance of ASIA, review the current evidence in support of the syndrome, and address recent reservations raised regarding its validity.
Asunto(s)
Adyuvantes Inmunológicos/efectos adversos , Enfermedades Autoinmunes/inmunología , Enfermedades Raras/inmunología , HumanosRESUMEN
Immune-mediated diseases of the central nervous system show wide variability both symptomatically and with respect to underlying pathophysiology. Recognizing aberrant immunologic activity as the cause of neurologic dysfunction requires establishing as precise a neuroanatomic and functional phenotype as possible, and a diagnostic and therapeutic strategy that stabilizes the patient, excludes broad categories of disease via rapidly available diagnostic assays, and maintains a broad differential diagnosis that includes immune-mediated conditions. This process is aided by recognizing the appropriate clinical circumstances under which immune-mediated disease should be suspected, and how to differentiate these conditions from other causes of similar neurologic dysfunction.
Asunto(s)
Enfermedades Autoinmunes del Sistema Nervioso/diagnóstico , Enfermedades Autoinmunes del Sistema Nervioso/inmunología , Enfermedades Raras/diagnóstico , Enfermedades Raras/inmunología , Niño , Diagnóstico Tardío , Diagnóstico Diferencial , Humanos , FenotipoAsunto(s)
Hidradenitis Supurativa/terapia , Enfermedades Raras/terapia , Antibacterianos/uso terapéutico , Terapia Biológica , Comorbilidad , Manejo de la Enfermedad , Predisposición Genética a la Enfermedad , Hidradenitis Supurativa/genética , Hidradenitis Supurativa/inmunología , Humanos , Enfermedades Raras/genética , Enfermedades Raras/inmunología , Investigación , Índice de Severidad de la EnfermedadRESUMEN
Autoimmune diseases are chronic, life threatening, and of burgeoning public health concern. They rank among the 10 most common causes of death in women, and some have incidence rates surpassing those of heart disease and cancer. Emerging information regarding molecular and cellular mechanisms affords opportunities for the discovery of novel therapeutic strategies or the repurposing of FDA-approved pharmacologic agents. Yet, obstacles to drug development amplify as an inverse function of the incidence of rare autoimmune disease; challenges include heterogeneous clinical presentation, paucity of definitive biomarkers, and poorly validated measures of therapeutic response. An integrative continuum model to address these challenges is being applied to neuromyelitis optica (NMO)-a potentially devastating neurodegenerative process that has had limited therapeutic options. This model links target discovery with pharmacologic application to accelerate improved clinical efficacy. The application of such innovative strategies may help researchers overcome barriers to therapeutic advances in NMO and other rare autoimmune diseases.