CONICET | Buscador de Institutos y Recursos Humanos

Background. Urea Cycle Disorders(UCD)comprise a group of metabolopatiessharing similar clinical phenotypes, in which acute hyperammonemia (HA)crises often occur. Among others, intercurrent infections have been empirically proposed as the main precipitants. Moreover, acute HA events following infections are clinically different from those triggered by other precipitants, representing a distinct clinical entity with increased morbidity. As infections are concurrent with HAevents, wehypothesized thatHAper se may induce animmunocompromised state causal of recurrent infections observed in patients. Methods.Different phenotypic and functional immune function parameters were assessed in UCD patients and healthy control volunteers. In vitrolymphoproliferation against different polyclonal and memory recall cell antigens, T helper cell subsets analyses by flow cytometry, cytokine secretion in culture supernatants, total immunoglobulin serum levels, and the glycosylation status of leukocyte cell surface proteins were assessed.Results.Similar lymphoproliferative responses to either polyclonal or memory recall cell antigens were observed in patientswith respect to controls. However, patients undergoingHA crisespresented significantlyreduced lymphoproliferation to different stimuli. Remarkably, significantly reduced counts of Th17 and Th1 cells, together with decreased IL17 and IFNɣsecretion levels, were observed in UCD patients.Moreover, monocytes and lymphocytes seem to display a different glycosylation pattern in conditions of HA. Discussion.These preliminary data show that UCD patients present alterations in different biomarkers of immune function, especially during HA crises, suggesting a state of immunocompromise which would renders patients more susceptible to infections. The latter would further aggravatethe HA status increasing the morbidity/mortality risk.