The effect of folinic acid supplementation on homocysteine concentrations in newborns.

OBJECTIVE: The incidence of cerebrovascular accidents (CVA) occurring perinatally is relatively high and aspects of the multifactorial pathophysiology remain unclear. Elevated homocysteine concentrations have been shown to be associated with an increased risk for CVA in children and even in newborns. We studied the possible homocysteine lowering effect of folinic acid in newborns. METHOD: We included 37 newborns in our prospective randomized folinic acid (given as 5-formyltetrahydrofolate) intervention study from patients admitted to our neonatal intensive care unit (18 controls, 19 intervention group). We measured total homocysteine (tHcy) and plasma folate concentrations at three time points (baseline, 1 and 2 weeks after intervention). The intervention group was treated with folinic acid (70 µg/kg/day) for 2 weeks. We calculated median concentrations (25th and 75th percentiles). RESULTS: Median tHcy concentrations at the three time points did not differ from each other in the control group nor in the intervention group. We also could not observe different tHcy concentrations between both groups. Plasma folate concentrations increased in the intervention group (mean increase 167% (95% confidence interval (CI) -291, 625)) compared with control group (mean increase -12% (95% CI -132, 108)), P for treatment effect: 0.03. CONCLUSION: We could not demonstrate a homocysteine lowering effect of folinic acid administration in newborns. This indicates that one carbon metabolism in newborns differs form adults. Cobalamin might be a better strategy to lower tHcy concentrations in newborns.

Epitope regions on U1 small nuclear RNA recognized by anti-U1RNA-specific autoantibodies.

Autoantibodies specifically directed to U1RNA were found in patients suffering from systemic lupus erythematosus (SLE) overlap syndromes. To obtain more insight in the mechanism responsible for this U1RNA-specific antibody formation and to use the antibodies eventually as a tool to study U1RNA-protein (U1RNP) interactions, the B cell epitopes on U1RNA were mapped. Using in vitro synthesized domains of U1RNA, the main epitope regions were found in stemloops II and IV. Furthermore, 3'-end or 5'-end truncation of both stemloop II and stemloop IV showed that the conformation of the stemloops is critical for antibody recognition. Mutant studies on both stemloops indicated that in the case of stemloop II the stem is the main antigenic region, whereas in stemloop IV, the loop (E-loop) is a main target. The results of this study support the idea that the anti-U1RNA autoantibody could be the result of a process driven by the human U1RNP complex itself (antigen-driven process).