ABSTRACT
Diminished neonatal antibody responses following infection or immunization may stem in part from intrinsic characteristics of neonatal B cells. In this study, we used B-cell subset sorting combined with gene expression assays to investigate major differences in the expression of host genes in neonatal and adult naïve B cells. We discovered significantly reduced expression of the interleukin (IL)-4 receptor alpha chain and reduced IL-4-induced signalling in neonatal B cells. Neonatal naïve B cells were susceptible to more rapid and more profound levels of apoptosis when cultured in vitro. They also exhibited a limited response to IL-4 treatment compared with adult cells. The expression level of the IL-13 receptor alpha 1 chain, a key component of the IL-13 receptor/IL-4 type II receptor, and the response to IL-13 treatment for protection against apoptosis in neonatal B cells were similar to those of the adult B cells. These studies suggest a possible mechanism underlying the limited magnitude and durability of neonatal antibody responses.
Subject(s)
B-Lymphocytes/metabolism , Interleukin-4 Receptor alpha Subunit/analysis , Signal Transduction/physiology , Adult , Analysis of Variance , Apoptosis , Cell Separation/methods , Fetal Blood/immunology , Flow Cytometry , Gene Expression , Humans , Infant, Newborn , Interleukin-13/pharmacology , Interleukin-13 Receptor alpha1 Subunit/metabolism , Interleukin-4/pharmacology , Interleukin-4 Receptor alpha Subunit/immunology , Phosphorylation , Reverse Transcriptase Polymerase Chain Reaction , STAT6 Transcription Factor/metabolismABSTRACT
OBJECTIVE: Pulmonary surfactant protein (SP)-B plays a vital role in the formation and function of surfactant in the lung. A genetic polymorphism (SP-B + 1580) is postulated to result in diminished activity of SP-B. The objective was to determine whether the SP-B + 1580 CC genotype is associated with an increased risk of respiratory failure and ARDS in adults with community-acquired pneumonia. DESIGN: Prospective cohort of adults diagnosed with community-acquired pneumonia. SETTING: Hospital system. PATIENTS: We enrolled 402 adults > or = 18 yrs of age with community-acquired pneumonia; 158 were white, 243 were African American, and one was Asian. INTERVENTIONS: Genotypic analysis was performed on DNA isolated from whole blood using polymerase chain reaction amplification and DdeI restriction enzyme digestion. MEASUREMENTS AND MAIN RESULTS: We recorded the requirement for mechanical ventilation, the presence of acute respiratory distress syndrome (ARDS) or septic shock, and mortality. Sixty-three patients required mechanical ventilation, 12 patients developed ARDS, and 35 patients developed septic shock. Genotypic frequencies at the SP-B + 1580 site were T/T 183 of 402 (0.45), T/C 160 of 402 (0.40), and C/C 59 of 402 (0.15). Of the 59 patients who were C/C at the SP-B + 1580 site, 21 (0.356) required mechanical ventilation, compared with 26 of 160 patients (0.163) who were T/C and 16 of 183 (0.087) patients who were T/T (p < .001). ARDS developed in five of 59 (0.085) patients with the C/C genotype, compared with six of 160 (.038) patients with T/C and one of 183 patients with T/T (0.005, p < .009). Septic shock occurred in 12 of 59 (0.203) patients with the C/C genotype, compared with 13 of 160 (0.081) patients with T/C and ten of 183 (0.055) patients with T/T (p < .001). Mortality rate was not different between the three genotypes. CONCLUSION: Carriage of the C allele at the SP-B + 1580 site is associated with ARDS, septic shock, and the need for mechanical ventilation in adults with community-acquired pneumonia.
