IMEX   05356
INSTITUTO DE MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Systemic autoinflammatory disease with intestinal bowel disease: what?s NLRP3 role? Case report
Autor/es:
BOUSO, CAROLINA; BUDA, GUADALUPE; JANCIC, CAROLINA C; DANIELIAN, SILVIA; ROCCA, ANA; ANTONISKA, MARIELA; BIAGIOLI, GERMÁN; MARTÍ, MARCELO; PRIETO, EMMA; YANCOSKI, JUDITH; OLEASTRO, MATÍAS
Lugar:
Cancún
Reunión:
Congreso; 6to Latin American Society for Immunodeficiencies (LASID); 2019
Resumen:
Introduction: NLRP3 belongs to the NOD-like receptors family of cytosolic PRR proteins. Its activation results in the inflammasome formation, with the subsequent production of mature interleukin (IL) 1β and 18. Pathogenic variants in NLRP3 have been formerly described as cryopyrinopathies (CINCA/NOMID, Muckle-Wells Syndrome, Familial Cold Urticaria), actually known as autoinflammatory diseases associated to NLRP3, with uncontrolled activation of this pathway.Objective: To describe a case of early-onset autoinflammatory disease with an unusual phenotype associated to an NLRP3 in silico predicted pathogenic variant.Case report: we present a non-dysmorphic girl, only daughter of non-consanguineous healthy parents, without family history of primary immunodeficiency. She started at 9 months of age with a systemic inflammatory process characterized by episodes of recurrent fever associated with subcutaneous nodules, and very-early-onset inflammatory bowel disease (VEOIBD) without evidence of infection. Blood tests showed leukocytosis (neutrophilia), thrombocytosis, elevated C-reactive protein and erythrocyte sedimentation rate, and normocytic normochromic anemia. Immunosuppressive treatment was started with good response to steroids, but poor response to 5-ASA and infliximab. A novel heterozygous NLRP3 variant in exon 3 (c.1307C>A) was then found through next-generation sequencing and confirmed by Sanger. This variant was not found in her parents (de novo); no other variants associated with her clinical evolution were found. Preliminary functional assays were performed in peripheral blood mononuclear cells revealing higher concentrations of IL-1β and IL-18 in patient?s samples compared to control. With these results, canakinumab therapy was started improving systemic symptoms like fever, acute phase reactants and skin lesions, although IBD persisted.Discussion: VEOIBD, associated with systemic inflammatory symptoms that are refractory to first-line therapy should raise the suspicion of an underlying monogenic disorder. A genetic and functionally proven diagnosis can guide towards specific therapeutic strategies. Although more functional assays are needed in order to confirm this variant as disease-causing, the patient didn?t improve with anti-TNF agents, but had a partial response to canakinumab. We hypothesize that other molecules besides IL-1β could be blocking targets in order to improve her IBD.