CONICET | Buscador de Institutos y Recursos Humanos

Introduction: Autoinflammatory diseases are inborn errors of the innate immune system. They present with uncontrolled systemic and organ specific inflammation, like infections, that generally associate inflammation of the skin and others organs since neonatal period and raised inflammatory markers in blood. Some may not have fever. In recent years, new mutations were discovered, as causes of primary immunodeficiencies. SAMD9L expression is high in B and NK lymphocytes, moderate in T cells, monocytes, neutrophils, lung and muscle and low in skin, liver, heart and kidney tissues. Missense mutation in SAMD9L can cause, an Early-Onset Immune- Dysregulation Syndrome of Neutrophilic Panniculitis, Interstitial Lung Disease and Cytopenias.Objectives: Report clinical case and immune reconstitution 3 years after bone marrow transplant in a patient with severe neonatal autoinflammatory syndrome due to SAMD9L mutation, with innate and adaptive immune compromise.Methods: Retrospective analysis of a clinical history and immune reconstitution in a patient with a new primary disease of immune dysregulation.Results: 3 years old girl, with chronic and generalized pustulosis since birth. At 2 months, persists with severe skin ulcers, no fever but high levels of CRP:78.5 mg/dl and ERS:68 mm3/h. In the immunological lab: hypogammaglobulinemia and almost absent B cell counts. Because of that she began treatment with intravenous gammaglobulin and corticosteroid, in spite of it she presented several skin exacerbations. So anti-TNF α (0.8 mg/dose weekly) treatment was added. She could improve skin lesions and almost normalized CRP but at fifth dose, she presented low platelets, white cells count and visceromegaly with respiratory failure because of Pneumocity Jiroveci and skin erythema and adenopathy at BCG site, needing mechanical ventilation, antibiotic, corticosteroid, cyclosporine and tuberculostatics drug because: positive Mycobacterium bovis in blood. After this treatment she presented partial response with marrow aplasia and she received canakinumab (ant IL-1β) 1 mg/kg/dose. No mutation in ADA2, TNFRSF1A, CECR1 and NLRP3 was found. Given the severe compromise, new studies were performed: Altered score for interferonopathies and mutation in SAMD9L protein was found by WES. Two months later, she was clinically stable. In 2016 she received unrelated HSCT (10/10). Nowadays she presents clinically well, no infections, only has mild rash in skin. No cytopenias, normal immunoglobulins, with B cell engraftment 15% (18,3 %B memory cells, 10,3% post switched memory cells and 3,2 % B transitional cells) Cd4 naïve T cells: 29,8% - 169 mm3, Normal NK compartment and T cells proliferations and normalized serum proinflammatory cytokines, with good evolution up to today and stopped GvHD treatment, only continue with weekly subcutaneous gammaglobulinConclusion: Severe autoinflammatory syndrome represent a challenge for clinical immunologists. HSCT was a curative treatment for our patient, who presented with a severe neonatal autoinflammation due to an immunodeficiency that affect innate and adaptive immune response