The highest alpha 2-macroglobulin concentrations were found in the PI Q0 patients (5 with emphysema, 2 with no lung disease), and these patients had almost no circulating alpha 1-antitrypsin.
The patient is heterozygous for an alteration in the A2M gene; this may be responsible for his serum A2M deficiency and may be relevant to the early onset of pulmonary disease in his case.
The patient is heterozygous for an alteration in the A2M gene; this may be responsible for his serum A2M deficiency and may be relevant to the early onset of pulmonary disease in his case.
The segregation of ABCA3 alleles, absence of ABCA3 immunostaining, lung pathology, and ultrastructural findings support genetic ABCA3 deficiency as the cause of lung disease in these 2 infants, despite the lack of an identified genetic variant.
To test the hypothesis that ABCA3 mutations modify the severity of lung disease in individuals with SFTPC mutations, we sequenced ABCA3 from four symptomatic infants with the same SFTPC mutation, a substitution of isoleucine by threonine in codon 73 (I73T).
ABCA3 is critical for the proper formation of lamellar bodies and surfactant function and may also be important for lung function in other pulmonary diseases.
Immunohistochemical analysis of surfactant protein expression in three patients revealed a specific staining pattern for surfactant protein-B, which was the same pattern observed in several infants with fatal lung disease due to ABCA3 mutations.
We report a case of siblings found to be compound heterozygotes for two novel ABCA3 gene mutations but developing very different course of lung disease.
This review summarizes current knowledge concerning clinical, genetic, and pathologic features of the lung disease associated with mutations in the ABCA3 gene, and also briefly reviews some other forms of childhood interstitial lung diseases that have their antecedents in the neonatal period and may also have a genetic basis.
The preferentially type 2 cell expressed genes involved in critical functions (such as ATP-binding cassette transporter, ABCA3), those involved in susceptibility to acute lung damage, and those with known susceptibility to other severe lung diseases (such as G protein-coupled receptor for asthma susceptibility, GPR154 alias GPRA) will possibly serve as candidate genes in future studies.
The preferentially type 2 cell expressed genes involved in critical functions (such as ATP-binding cassette transporter, ABCA3), those involved in susceptibility to acute lung damage, and those with known susceptibility to other severe lung diseases (such as G protein-coupled receptor for asthma susceptibility, GPR154 alias GPRA) will possibly serve as candidate genes in future studies.
These findings show that Notch1 and MRP1 might have a potential protective effect in the COPD process and become a new therapeutic target for COPD or other lung diseases.
These results establish a critical role for T2 cell ABCG1 in controlling surfactant and overall lipid homeostasis in the lung and in the pathogenesis of human lung disease.