Relationship between age at initiation of cysteamine treatment, adherence with therapy, and glomerular kidney function in infantile nephropathic cystinosis.

Infantile nephropathic cystinosis, due to impaired transport of cystine out of lysosomes, occurs with an incidence of 1 in 100-200,000 live births. It is characterized by renal Fanconi syndrome in the first year of life and glomerular dysfunction progression to end-stage kidney disease by approximately 10 years of age. Treatment with oral cysteamine therapy helps preserve glomerular function, but affected individuals eventually require kidney replacement therapy. This is because glomerular damage had already occurred by the time a child is diagnosed with cystinosis, typically in the second year of life. We performed a retrospective multicenter study to investigate the impact of initiating cysteamine treatment within the first 2 months of life in some infants and comparing two different levels of adherence in patients diagnosed at the typical age. We collected 3983 data points from 55 patients born between 1997 and 2020; 52 patients with 1592 data points could be further evaluated. These data were first analyzed by dividing the patient cohort into three groups: (i) standard treatment start with good adherence, (ii) standard treatment start with less good adherence, and (iii) early treatment start. At every age, mean estimated glomerular filtration rate (eGFR) was higher in early-treated patients than in later-treated patients. Second, a generalized additive mixed model (GAMM) was applied showing that patients with initiation of treatment before 2 months of age are expected to have a 34 ml/min/1.73 m2 higher eGFR than patients with later treatment start while controlling for adherence and patients' age. These data strongly suggest that oral cysteamine treatment initiated within 2 months of birth preserves kidney function in infantile nephropathic cystinosis and provide evidence of the utility of newborn screening for this disease.

Mannose-binding lectin and mannose-binding protein-associated serine protease 2 levels and infection in very-low-birth-weight infants.

OBJECTIVE: The aim of this study was to explore the role of the lectin pathway in neonatal sepsis through the study of MBL and MASP2 levels and their relationship with infection in a cohort of very-low-birth-weight infants (VLBWI). METHODS: MBL and MASP2 were measured in plasma samples of n = 89 VLBWI using ELISA and correlated with clinical parameters. MBL plasma levels were aligned with genotyping data of mbl2 exon 1 polymorphisms, rs1800450, rs1800451, and rs5030737. RESULTS: MBL levels were clearly determined by MBL genotype, i.e., AA individuals had tenfold higher MBL levels than AO individuals. MBL and MASP2 levels did not correlate with gestational age, apart from MASP2 levels on day 7. During the first 21 days of life, we noted a gradual increase in both MBL and MASP2 levels. On day 7 of life, MASP2 levels in infants developing late-onset sepsis measured before the onset of symptoms were found to be lower, as compared to non-LOS infants. CONCLUSIONS: In our cohort of VLBWI, MBL levels were genetically determined, but not associated with gestational age or sepsis in the first 21 days of life. Lower MASP2 levels on day 7 may indicate increased risk for late-onset infection.

Differential expression of antimicrobial polypeptides in cord blood samples of preterm and term infants.

AIM: To determine levels of antimicrobial polypeptides (AMP) in cord blood of term and preterm neonates and to investigate influencing factors. METHODS: In a single-centre study, n = 139 preterm infants and n = 36 term infants were included. AMP levels were analysed in supernatants of whole cord blood cultures with a standardised concentration of 5 × 10(6) white blood cells/mL via enzyme-linked immunosorbent assay (ELISA). RESULTS: Lactoferrin, human neutrophil peptides (HNP) 1-3 and bacterial permeability-increasing protein (BPI) expression in cord blood of preterm infants were influenced by the cause of preterm delivery, that is increased levels in infants with clinical amniotic infection. AMP levels also weakly correlated with white blood cell and neutrophil count at birth. In the whole cohort, no association between gestational age or birthweight with AMP levels was found. In the subgroup of infants without clinical amniotic infection (n = 77 preterm infants, n = 36 healthy term infants), we noted a weak correlation between gestational age and lactoferrin, calprotectin and HNP1-3 levels. In addition to that, we observed higher levels of lactoferrin and HNP1-3 in large-for-gestational-age infants. CONCLUSION: Our study confirms that several factors influence cord blood AMP levels which underlines the difficulties of using AMP levels as biomarkers of immunological response.

Lactoferrin and Human Neutrophil Protein (HNP) 1-3 Levels During the Neonatal Period in Preterm Infants.

Antimicrobial polypeptides (APPs) are part of the innate immune system, but their specific role in the context of preterm birth is not yet understood. The aim of this investigation was to determine the systemic expression of APPs, i.e., lactoferrin (LF) and human neutrophil protein (HNP) 1-3 in preterm infants in the period of highest vulnerability for infection and to correlate these biomarkers with short-term outcome. We therefore conducted a prospective two-center study including plasma samples of 278 preterm infants and 78 corresponding mothers. APP levels were analyzed on day 1, 3, 7, and 21 of life via enzyme-linked immunosorbent assay (ELISA). The levels of LF and HNP1-3 remained stable during the first 21 days of life and were not influenced by maternal levels. Elevated APP levels were found at day 1 in infants born to mothers with amniotic infection syndrome (AIS vs. no AIS, mean ± SD in ng/ml: LF 199.8 ± 300 vs. 124.1 ± 216.8, HNP 1-3 16,819 ± 36,124 vs. 8,701 ± 11,840; p = 0.021, n = 179). We found no elevated levels of APPs before the onset of sepsis episodes or in association with other short-term outcomes that are in part mediated by inflammation such as necrotizing enterocolitis (NEC) or retinopathy of prematurity (ROP). Interestingly, infants developing bronchopulmonary dysplasia (BPD) showed higher levels of HNP1-3 on day 21 than infants without BPD (13,473 ± 16,135 vs. 8,388 ± 15,938, n = 111, p = 0.008). In infants born without amniotic infection, levels of the measured APPs correlated with gestational age and birth weight. In our longitudinal study, systemic levels of LF and HNP 1-3 were not associated with postnatal infection and adverse short-term outcomes in preterm infants.