IMMUNE ALTERATIONS IN ARGENTINE PATIENTS WITH CONGENITAL UREA CYCLE METABOLIC DISORDERS

PAIRA, DANIELA A.; BECERRA, A; LAROVERE, LAURA E.; PEANO, NATALIA; MOTRICH, RUBEN D.; SILVERA-RUIZ, SILENE M.; OLIVERA, CAROLINA; DODELSON-KREMER, RAQUEL

Congreso; REUNIÓN DE SOCIEDADES DE BIOCIENCIAS 2020; 2020

Sociedad Argentina de Inmunologia

Background. Urea Cycle Disorders (UCD) comprise a group of metabolopathies sharing 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 HA events, we hypothesized that HA may per se induce an immunocompromised state that would be causal of the observed recurrent infections. Methods. Different phenotypic and functional immune function parameters were assessed in UCD patients and healthy control volunteers. In vitro lymphoproliferation against different polyclonal and memory recall cell antigens, T helper cell subset frequencies, cytokine secretion in culture supernatants, total immunoglobulin serum levels, and the glycosylation status of leukocyte cell surface proteins were assessed. Results. A state of marked hypogammaglobulinemia was detected in UCD patients. Conversely, similar lymphoproliferative responses to either polyclonal or memory recall cell antigens were observed in patients with respect to controls. However, patients undergoing HA crises presented significantly reduced lymphoproliferation to different stimuli. Remarkably, significantly reduced counts of Th17 and Th1 cells, together with decreased IL17 and IFNɣ secretion levels, were observed in UCD patients. Moreover, monocytes and lymphocytes seem to display an altered glycosylation pattern in conditions of HA. Discussion. These preliminary data indicate that UCD patients present alterations in different biomarkers of immune function, especially during HA crises, suggesting a state of immunocompromise that would render patients susceptible to infections. The latter would further aggravate the HA status increasing the morbidity/mortality risk.