OBJECTIVE: To analyze the association between pulmonary surfactant protein C (SP-C) gene polymorphisms and the risk of Neonatal respiratory distress syndrome (NRDS). METHODS: Clinical data from 168 neonates diagnosed with NRDS (NRDS group) admitted between August 2020 and June 2023 were collected. Additionally, 168 neonates without respiratory distress, born during the same period, were included as the control group. Peripheral venous blood samples (2 mL each) were collected from both groups. PCR-restriction fragment length polymorphism technique was employed to detect the polymorphisms at the SP-C gene loci p.Thr138Asn (rs4715) and p.Ser186Asn (rs1124). Hardy-Weinberg equilibrium tests were conducted for genotyping, and genotypic and allelic frequencies were compared. The association between SP-C gene polymorphisms and NRDS risk was evaluated. Furthermore, genotypic and allelic frequencies at the rs4715 and rs1124 loci were compared among NRDS cases with varying degrees of disease severity. The study was approved by the Medical Ethics Committee of Shangqiu First People's Hospital (Ethics No. 2020-031). RESULTS: The frequency of the variant allele (A) at the rs4715 locus was significantly higher in the NRDS group compared to the control group (32.14% vs. 24.11%, P = 0.001). The frequency of the variant genotype (AA + AC) was also higher in the NRDS group (47.02% vs. 39.29%, P = 0.043). The frequency of the variant allele (A) at the rs1124 locus was higher in the NRDS group compared to the control group (34.23% vs. 23.51%, P = 0.027), with a higher frequency of the variant genotype (AA + AG) in the NRDS group (49.40% vs. 39.29%, P = 0.019). No significant correlation was observed between the rs4715 polymorphism and the severity of NRDS (P > 0.05). Among NRDS children with grade III severity, the frequency of the variant allele (A) at the rs1124 locus was higher than in grade I and grade II children (47.62% vs. 29.22%, P = 0.020). The frequency of the variant genotype (AA + AG) was also higher in grade III children (64.28% vs. 43.84%, P = 0.040). CONCLUSION SP-C gene polymorphisms are associated with the susceptibility to NRDS. Neonates carrying the AA genotype and the A allele at the rs1124 locus are at a higher risk of severe NRDS. These findings have provided further evidence for early screening, diagnosis, and treatment of NRDS.
Humans ; Respiratory Distress Syndrome, Newborn/genetics* ; Infant, Newborn ; Gene Frequency ; Genotype ; Polymorphism, Single Nucleotide ; Pulmonary Surfactant-Associated Protein C/genetics* ; Genetic Predisposition to Disease ; Female ; Male ; Alleles

Pulmonary surfactant (PS) is synthesized and secreted by alveolar epithelial type II (AEII) cells, which is a complex compound formed by proteins and lipids. Surfactant participates in a range of physiological processes such as reducing the surface tension, keeping the balance of alveolar fluid, maintaining normal alveolar morphology and conducting host defense. Genetic disorders of the surfactant homeostasis genes may result in lack of surfactant or cytotoxicity, and lead to multiple lung diseases in neonates, children and adults, including neonatal respiratory distress syndrome, interstitial pneumonia, pulmonary alveolar proteinosis, and pulmonary fibrosis. This paper has provided a review for the functions and processes of pulmonary surfactant metabolism, as well as the connection between disorders of surfactant homeostasis genes and lung diseases.
ATP-Binding Cassette Transporters ; genetics ; DNA-Binding Proteins ; genetics ; Homeostasis ; Humans ; Lung Diseases ; genetics ; Pulmonary Surfactant-Associated Protein C ; genetics ; Pulmonary Surfactants ; metabolism ; Transcription Factors

PURPOSE: Pulmonary surfactant (PS) replacement has been the gold standard therapy for neonatal respiratory distress syndrome; however, almost all commercial PSs contain animal proteins. We prepared a synthetic PS by using a human surfactant protein (SP) analog and evaluated its in vitro properties. MATERIALS AND METHODS: A peptide sequence (CPVHLKRLLLLLLLLLLLLLLLL) of human SP-C was chosen to develop the peptide analog (SPa-C). The new synthetic SP-C PS (sSP-C PS) was synthesized from SPa-C, dipalmitoyl phosphatidylcholine, phosphatidyl glycerol, and palmitic acid. Physical properties of the sSP-C PS were evaluated by measuring the maximum and minimum surface tensions (STs), surfactant spreading, and adsorption rate. In addition, we recorded an ST-area diagram. The data obtained on sSP-C PS were subsequently compared with those of purified natural bovine surfactant (PNBS), and the commercial product, Surfacten(R). RESULTS: The sSP-C PS and Surfacten(R) were found to have maximum ST values of 32-33 mN/m, whereas that of PNBS was much lower at 19 mN/m. The minimum ST values of all three products were less than 10 mN/m. The values that were measured for the equilibrium ST of rapidly spreading sSP-C PS, Surfacten(R), and PNBS were 27, 27, and 24 mN/m, respectively. The surface adsorptions were found to be the same for all three PSs (20 mN/m). ST-area diagrams of sSP-C PS and Surfacten(R) revealed similar properties. CONCLUSION: In an in vitro experiment, the physical properties exhibited by sSP-C PS were similar to those of Surfacten(R). Further study is required to evaluate the in vivo efficacy.
1,2-Dipalmitoylphosphatidylcholine/analogs & derivatives ; Adsorption ; Amino Acid Sequence/*genetics ; Animals ; C-Peptide/*chemistry ; Cattle ; Humans ; Infant, Newborn ; Pulmonary Surfactant-Associated Protein C/*chemical synthesis/pharmacology ; Pulmonary Surfactants/*chemical synthesis/pharmacology ; Respiratory Distress Syndrome, Newborn/*drug therapy ; *Surface Properties ; *Surface Tension ; Surface-Active Agents

OBJECTIVETo report a case of I73T mutation in the pulmonary surfactant protein (SP)-C gene associated with pediatric interstitial lung disease, and study the clinical diagnosis and review related literature, to investigate the role of gene detection in the diagnosis of interstitial lung disease in infants and children.

METHODThe clinical, radiological, and genetic testing information of the case was analyzed and related literature was reviewed.

RESULT(1) An 8-month-old girl was hospitalized because of cough, tachypnea, continuous oxygen therapy and failure to thrive. Physical examination on admission revealed tachypnea, slight cyanosis and the three concave sign was positive, respiratory rate of 50 times/minute, scattered fine crackles could be heard over both lungs, clubbing fingers were found. No other abnormalities were noted. Laboratory test results: pathogenic examination was negative, multiple blood gas analysis suggested hypoxemia. Chest CT showed ground-glass like opacity, diffused tubercle infiltration. The I73T mutation in SP-C gene was identified by SP-related gene sequencing. (2) The review of related literature: Data of 3 infants with I73T mutation in SP-C gene showed that all the 3 cases had tachypnea and dyspnea, chest CT revealed diffuse infiltration or diffuse ground glass pattern in lungs, the major pathology of lungs was nonspecific interstitial pneumonia (NSIP).

CONCLUSIONA case of interstitial lung disease with I73T mutation in SP-C gene was preliminarily diagnosed in an infant. Gene test provides an important tool in the diagnosis of such pediatric interstitial lung disease.

Dyspnea ; Female ; Humans ; Idiopathic Interstitial Pneumonias ; Infant ; Lung Diseases, Interstitial ; diagnosis ; genetics ; Mutation ; Pulmonary Surfactant-Associated Protein C ; genetics ; Pulmonary Surfactants ; Tomography, X-Ray Computed

Cell Line ; Clustered Regularly Interspaced Short Palindromic Repeats ; genetics ; DNA ; metabolism ; Deoxyribonuclease I ; metabolism ; Embryonic Stem Cells ; cytology ; metabolism ; Homologous Recombination ; Humans ; Pulmonary Surfactant-Associated Protein C ; genetics

OBJECTIVETo report a case of pulmonary surfactant protein (SP) gene mutation associated with pediatric interstitial lung disease, and study the clinical diagnosis process and review of related literature, to understand the relationship between interstitial lung disease and SP gene mutation in infants and children.

METHODThe clinical, radiological, histological, and genetic testing information of a case of SP gene mutation related pediatric interstitial lung disease were analyzed and related literature was reviewed.

RESULTA 2-year-old girl without a history of serious illness was hospitalized because of the shortness of breath, cough, excessive sputum, and the progressive dyspnea. Physical examination on admission revealed tachypnea, slight cyanosis, and the retraction signs were positive, respiratory rate of 60 times/minute, fine crackles could be heard through the lower lobe of both lungs; heart rate was 132 beats/minute. No other abnormalities were noted, no clubbing was found. Laboratory test results: pathologic examination was negative, multiple blood gas analysis suggested hypoxemia. Chest CT showed ground-glass like opacity, diffused patchy infiltration. Bronchoalveolar lavage fluid had a large number of neutrophils, and a few tissue cells. Eosinophil staining: negative. Fluconazole and methylprednisolone were given after admission, pulmonary symptoms and signs did not improve, reexamination showed no change in chest CT. Then lung biopsy was carried out through thoracoscopy. Histopathology suggested chronic interstitial pneumonia with fibrosis. The heterozygous mutation of R219W in the SFPTA1 and the S186N in SFTPC were identified by SP-related gene sequencing. The review of related literature showed that polymorphisms at the 219th amino acid in SP-A1 allele were found in adults with idiopathic pulmonary fibrosis (IPF), but there is no related literature in pediatric cases. The patient in this report had a mutation at the SP-A1 allele consistent with related literature. Data of 17 young children with mutation in SP-C gene showed that all the 17 cases had dyspnea and tachypnea, chest CT revealed diffuse opacities in lungs, the pathology of lungs was NSIP and CPI. There were 17 kinds of mutation and the common mutation was I73T. The mutation of S186N in SFTPC in our case has never been shown in previously published literature.

CONCLUSIONA case of interstitial lung disease with S186N gene mutation in SFTPC was preliminarily diagnosed in an infant. The SP-C gene mutations and polymorphisms are associated with pediatric interstitial lung disease.

Biopsy ; Child, Preschool ; DNA Mutational Analysis ; Dyspnea ; diagnosis ; pathology ; Female ; Humans ; Infant ; Lung ; diagnostic imaging ; pathology ; Lung Diseases, Interstitial ; diagnosis ; genetics ; pathology ; Male ; Mutation ; Pulmonary Surfactant-Associated Protein C ; genetics ; Tomography, X-Ray Computed

OBJECTIVETo explore the prevalence of pulmonary surfactant associated pathway genes functional variants in Chinese population.

METHODUsing a cohort of 258 mixed ethnic population of Han and Zhuang, we pooled DNA samples from 146 term male infants and 112 term female infants and then used an Ill umina next generation sequencing platform to perform the complete exonic resequencing in 6 target genes:surfactant protein-B (SFTPB), surfactant protein-C (SFTPC), ATP-binding cassette transporter A3 (ABCA3), lysophospholipid acyltransferase 1 (LPCAT1), choline phosphotransferase 1 (CHPT1), phosphate cytidylyltransferase 1, choline, beta (PCYT1B). Collapsing methods was used to determine the functional allele frequency.

RESULT(1) Altogether, 128 variants were found, including 44 synonymous variants, 66 nonsynonymous variants and 18 insertions-deletions. Of these, 28 variants were predicted to alter protein function. Two of these variants were seen twice, the rest variants were only seen once, for a total of 30 functional alleles; (2) ABCA3 had the most functional variants in both male and female groups with the minor allele frequencies of 0.014 (1.4%) and 0.04 (4%), respectively. The total functional allele frequencies of 6 genes were 0.041 (4.1%) and 0.08 (8%) in the two groups, respectively (P = 0.06).

CONCLUSION(1) Functional variants in pulmonary surfactant associated pathway genes are present in the mixed Han-Zhuang population. (2) ABCA3 contained the most functional variants suggesting that ABCA3 could contribute significantly to neonatal respiratory distress syndrome and other lung disease.

1-Acylglycerophosphocholine O-Acyltransferase ; genetics ; metabolism ; ATP-Binding Cassette Transporters ; genetics ; Asian Continental Ancestry Group ; ethnology ; genetics ; China ; ethnology ; Female ; Gene Frequency ; Genetic Association Studies ; Genetic Predisposition to Disease ; Genetic Variation ; Genotype ; Humans ; Infant, Newborn ; Male ; Pulmonary Surfactant-Associated Protein C ; genetics ; Pulmonary Surfactant-Associated Proteins ; genetics ; Respiratory Distress Syndrome, Newborn ; ethnology ; genetics

OBJECTIVETo review the pathophysiology, evaluation, management, and outcomes of children with inherited disorders of surfactant metabolism due to mutations in the genes encoding surfactant proteins-B or -C (SFTPB, SFTPC), ATP binding cassette member A3 (ABCA3), and thyroid transcription factor (NKX2.1).

DATA SOURCESReview of the literature, previous work from the author's and collaborators' laboratories, St. Louis Children's Hospital Lung Transplant Database.

STUDY SELECTIONKey articles in the field, author's work.

RESULTSInherited disorders of surfactant metabolism present as acute, severe respiratory dysfunction in the neonatal period (SFTPB, ABCA3, NKX2.1) or as chronic respiratory insufficiency in later infancy and childhood which is of variable onset, severity, and course (SFTPC, ABCA3, NKX2.1). Diagnosis is established with sequencing the relevant genes; lung biopsy with electron microscopy is a useful adjunct. For surfactant protein-B and ABCA3 deficiency presenting with acute neonatal disease, treatment options are limited to lung transplantation or compassionate care. For the more chronic presentations of surfactant protein-C, ABCA3, and NKX2.1 associated disease, the natural history is variable and therefore individualized, supportive care is appropriate,

CONCLUSIONSInherited disorders of surfactant metabolism are rare, but informative diseases that provide unique opportunities for understanding mechanisms of respiratory disease in newborns and children.

ATP-Binding Cassette Transporters ; genetics ; Humans ; Infant, Newborn ; Lung Diseases ; diagnosis ; etiology ; therapy ; Lung Transplantation ; Mutation ; Pulmonary Surfactant-Associated Protein B ; deficiency ; genetics ; Pulmonary Surfactant-Associated Protein C ; genetics ; Pulmonary Surfactants ; metabolism

Dendritic-cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN; CD209) has an important role in mediating adherence of Mycobacteria species, including M. tuberculosis and M. bovis BCG to human dendritic cells and macrophages, in which these bacteria can survive intracellularly. DC-SIGN is a C-type lectin, and interactions with mycobacterial cells are believed to occur via mannosylated structures on the mycobacterial surface. Recent studies suggest more varied modes of binding to multiple mycobacterial ligands. Here we identify, by affinity chromatography and mass-spectrometry, four novel ligands of M. bovis BCG that bind to DC-SIGN. The novel ligands are chaperone protein DnaK, 60 kDa chaperonin-1 (Cpn60.1), glyceraldehyde-3 phosphate dehydrogenase (GAPDH) and lipoprotein lprG. Other published work strongly suggests that these are on the cell surface. Of these ligands, lprG appears to bind DC-SIGN via typical proteinglycan interactions, but DnaK and Cpn60.1 binding do not show evidence of carbohydrate-dependent interactions. LprG was also identified as a ligand for DC-SIGNR (L-SIGN; CD299) and the M. tuberculosis orthologue of lprG has been found previously to interact with human toll-like receptor 2. Collectively, these findings offer new targets for combating mycobacterial adhesion and within-host survival, and reinforce the role of DCSIGN as an important host ligand in mycobacterial infection.
Amino Acid Sequence ; Bacterial Adhesion ; physiology ; Bacterial Proteins ; genetics ; metabolism ; Cell Adhesion Molecules ; genetics ; metabolism ; Chromatography, Affinity ; Dendritic Cells ; metabolism ; microbiology ; Host-Pathogen Interactions ; genetics ; physiology ; Humans ; In Vitro Techniques ; Lectins, C-Type ; genetics ; metabolism ; Ligands ; Macrophages ; metabolism ; microbiology ; Mass Spectrometry ; Membrane Proteins ; genetics ; metabolism ; Models, Biological ; Molecular Chaperones ; genetics ; metabolism ; Molecular Sequence Data ; Mycobacterium bovis ; genetics ; metabolism ; Mycobacterium tuberculosis ; genetics ; metabolism ; pathogenicity ; Pulmonary Surfactant-Associated Protein A ; metabolism ; Receptors, Cell Surface ; genetics ; metabolism

OBJECTIVEAlveolar epithelium impairment is one of pathological changes associated with chronic lung disease (CLD). Hoxb5 is one of the few homeobox genes strongly expressed in the developing lung. This study investigated the expression of HoxB5, SPC and AQP5 in rats with CLD in order to explore the role of Hoxb-5 in impairment and reparation of alveolar epithelium.

METHODSEighty neonatal rats were randomly exposed to hyperoxia (model group) or to room air (control group) (n=40 each). The CLD model was induced by hyperoxia exposure. The expression of HoxB5, SPC and AQP5 protein and mRNA in the lung tissue was detected by immunohistochemistry and RT-PCR 1, 3, 7, 14 and 21 days after exposure.

RESULTSIn the model group HoxB5 expression significantly decreased 7, 14 and 21 days after hyperoxia exposure. SPC expression decreased 3 days after hyperoxia exposure but increased significantly 7, 14 and 21 days after hyperoxia exposure as compared to the control group. AQP5 expression was progressively reduced with prolonged hyperoxia exposure.

CONCLUSIONSHyperoxia exposure may lead to alveolar epithelial cell (AEC) damage in neonatal rats. The increased SPC expression and decreased AQP5 expression suggested that the ability of differentiation and transformation of AECII into AECI decreased in neonatal rats with CLD. The decreased HoxB5 expression following hyperoxia exposure might contribute to a decreased ability of differentiation of AECII.

Animals ; Animals, Newborn ; Aquaporin 5 ; analysis ; genetics ; Chronic Disease ; Female ; Homeodomain Proteins ; analysis ; genetics ; Hyperoxia ; complications ; Immunohistochemistry ; Lung ; pathology ; Lung Diseases ; etiology ; metabolism ; Male ; Pulmonary Surfactant-Associated Protein C ; analysis ; genetics ; RNA, Messenger ; analysis ; Rats ; Rats, Wistar ; Reverse Transcriptase Polymerase Chain Reaction