W155 - Immune Alterations in Patients with Congenital Urea Cycle Disorders

Silene Silvera-Ruiz – FOCIS-FCE Centro de Inmunologia Clinica de Cordoba (CICC). CIBICI-CONICET. Facultad de Ciencias Quimicas. Universidad Nacional de Cordoba.; Daniela Paira – FOCIS-FCE Centro de Investigación en Inmunología Clínica de Córdoba (CICC). CIBICI-CONICET. Facultad de Ciencias Químicas. Universidad Nacional de Córdoba. Córdoba. Argentina.; Maria Martinez – PhD student, FOCIS-FCE Centro de Investigación en Inmunología Clínica de Córdoba (CICC). CIBICI-CONICET. Facultad de Ciencias Químicas. Universidad Nacional de Córdoba. Córdoba. Argentina.; Yair Chocobar – FOCIS-FCE Centro de Investigación en Inmunología Clínica de Córdoba (CICC). CIBICI-CONICET. Facultad de Ciencias Químicas. Universidad Nacional de Córdoba. Córdoba. Argentina.; Natalia Peano – Fundación para el Progreso de la Medicina. Córdoba. Argentina.; Adriana Becerra – FOCIS-FCE Centro de Inmunologia Clinica de Cordoba (CICC). CIBICI-CONICET. Facultad de Ciencias Quimicas. Universidad Nacional de Cordoba.; Olga Gornik – Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia.; Toma Keser – Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia.; Adriana Gruppi – FOCIS-FCE Centro de Inmunologia Clinica de Cordoba (CICC). CIBICI-CONICET. Facultad de Ciencias Quimicas. Universidad Nacional de Cordoba.; Carola Grosso – FOCIS-FCE Centro de Inmunologia Clinica de Cordoba (CICC). CIBICI-CONICET. Facultad de Ciencias Quimicas. Universidad Nacional de Cordoba.; Laura Larovere – FOCIS-FCE Centro de Inmunologia Clinica de Cordoba (CICC). CIBICI-CONICET. Facultad de Ciencias Quimicas. Universidad Nacional de Cordoba.

Abstract Text: Urea Cycle Disorders (UCD) comprise a group of metabolopathies sharing similar clinical phenotypes, in which acute hyperammonemia (AH) crises occur often. Interestingly, intercurrent infections are the most frequent and dangerous precipitant of AH and metabolic decompensation. Although concurrent, it is currently unknown whether infections are associated with immunological alterations in these patients.
Thus, we herein analyzed different phenotypic and functional immune function parameters in UCD patients and healthy controls. In vitro lymphoproliferation against different polyclonal and memory recall cell antigens, T helper cell subsets, cytokine secretion in culture supernatants, total immunoglobulin serum levels, and the glycosylation status of serum immunoglobulins, were analyzed.
Similar lymphoproliferative responses to either polyclonal or memory recall cell antigens were observed in patients with respect to controls. However, significantly reduced counts of Th17 and Th1 cells and decreased IL17 and IFNɣ secretion levels were observed in patients with respect to controls. Moreover, patients revealed significantly higher proportions of terminally differentiated effector memory (TEMRA) CD4 and CD8 T cells. Besides, a state of marked hypogammaglobulinemia associated with significantly reduced frequencies of plasmablasts and memory B cells was detected in UCD patients. Moreover, serum immunoglobulins displayed a strikingly altered glycosylation pattern.
These data show that UCD patients present alterations in different biomarkers of immune function, suggesting a state of immunocompromise that would renders patients more susceptible to infections. The latter would further aggravate the HA status increasing the morbidity/mortality risk.