Neutrophil-mediated inflammation in respiratory syncytial viral bronchiolitis.

BACKGROUND: The involvement of neutrophil-mediated inflammation may play an important role in the pathogenesis of acute respiratory syncytial virus bronchiolitis. However, no measurable marker is sensitive enough to assess neutrophil-mediated inflammation in the airways. Released neutrophil elastase (NE) in intraluminal airways has been reported to induce pulmonary inflammation. The aim of this study was to determine whether the amount of urinary trypsin inhibitor (UTI) in serum, a degenerate induced by NE, reflects the degree of airway inflammation in children with respiratory syncytial viral (RSV) bronchiolitis and whether the severity of inflammation is evaluated. The pre-alpha-/inter-alpha-trypsin inhibitor is assumed to be precursors of the UTI. When NE degrades these inhibitors, UTI is liberated. METHODS: Serum UTI concentrations in infants admitted with RSV bronchiolitis, other viral infections, bacterial pneumonia and control subjects were measured by means of one-step sandwich-type enzyme immunoassay. RESULTS: Serum UTI concentrations in 25 patients on admission were significantly higher than the 15 infantile control values (mean +/- SEM, 22.126 +/- 2.317 and 6.701 +/- 0.719 U/mL, respectively; P < 0.0001). The elevated levels returned to baseline values with improvement in the respiratory symptoms. Higher levels of serum UTI with RSV infection were consistently associated with clinical symptoms and artificial ventilation. Serum NE concentrations of patients were elevated in some patients but not significantly different from controls in the patients who showed only upper respiratory symptoms with RSV infections. CONCLUSION: The findings strongly suggested that neutrophil-mediated events are involved in the pathogenesis of RSV bronchiolitis, and the monitoring of UTI concentrations might be useful for evaluating the neutrophil-mediated airway inflammation.

Serologic analysis of three cases of neonatal alloimmune thrombocytopenia associated with HLA antibodies.

BACKGROUND: Neonatal alloimmune thrombocytopenia (NAIT) is caused when maternal alloantibodies react with paternally inherited antigens present on the fetal PLTs, a reaction mainly due to antibodies against human PLT antigens. Cases in which NAIT has been caused by HLA antibodies are relatively rare. In this study, three cases of NAIT associated with HLA antibodies that occurred in a 1-year period are reported. STUDY DESIGN AND METHODS: The presence of HLA antibodies in these three NAIT case studies was elucidated by examining reactions of the neonatal and maternal sera with lymphocytes, PLTs, and beads from an HLA antibody screening test (FlowPRA, One Lambda Inc.). Absorption and elution tests with paternal cells were also conducted. In addition, the influence of titer and specificity of HLA antibodies on NAIT was analyzed in light of 24 other documented cases in Japan. RESULTS: In the three case studies presented herein, antibodies against human PLT antigens were found in neither the maternal nor neonatal sera, while specific HLA antibodies were identified in both sera. Absorption of maternal serum with paternal PLTs eliminated the reactivity against paternal PLTs and lymphocytes. CONCLUSION: Transplacental passage of maternal HLA antibodies was observed in the three neonates cited in the present study.

Single base substitutions at the initiator codon in the mitochondrial acetoacetyl-CoA thiolase (ACAT1/T2) gene result in production of varying amounts of wild-type T2 polypeptide.

Initiator codon mutations are relatively uncommon and less well characterized compared to other types of mutations. We identified a novel initiator codon mutation (c.2T>C) heterozygously in a Japanese patient (Patient GK30) with mitochondrial acetoacetyl-CoA thiolase (T2) gene deficiency (ACAT1 deficiency); c.149delC was on the other allele. We examined translation efficiencies of nine mutant T2 cDNAs harboring one-base substitutions at the initiator methionine codon using in vivo transient expression analysis. We found that all the mutants produced wild-type T2 polypeptide, to various degrees (wild type (100%) > c.1A>C (66%) > c.2T>C, c.3G>C, c.3G>T (22%) > c3G>A, c.1A>G (11%) > c.2T>A, c.2T>G, c.1A>T (7.4%)). T2 mRNA expression levels in Patient GK08 (a homozygote of c.2T>A) and Patient GK30 fibroblasts, respectively, were almost the same as in control fibroblasts, when examined using semiquantitative PCR. This means that initiator codon mutations did not affect T2 mRNA levels. We propose that all one-base substitutions at the initiator methionine codon in the T2 gene could be mutations, which retain some residual T2 activity.