[Clinical, biological and genetic heterogeneity of the inborn errors of pulmonary surfactant metabolism: SP-B deficiency and alveolar proteinosis].
Pulmonary surfactant is a multimolecular complex located at the air-water interface within the alveolus and to which a bulk of functions has been assigned, physical (surface-active properties) as well as immune or depurant. This complex consists of a surface active lipid layer (mainly phospholipids), and of an aqueous subphase. From discrete surfactant sub-fractions, one can isolate very hydrophobic proteins SP-B and SP-C as well as the collectins SP-A and SP-D, which were shown to have structural, metabolic, or defensive properties. Inborn or acquired abnormalities of surfactant, qualitative or quantitative in nature, account for a number human diseases. Beside hyaline membrane disease of the preterm neonate, a cluster of hereditary or acquired lung diseases have been characterized by the storage of periodic acid Schiff-positive material filling the alveoli. From this heterogeneous nosologic bulk, at least two discrete entities presently seem to emerge: 1) SP-B deficiency, in which an essentially proteinaceous material is stored within the alveoli, and which is a bona fide autosomal recessive Mendelian entity linked to the SFTPB gene (MIM 1786640), generally entailing neonatal respiratory distress with rapid fatal outcome, although partial or transient deficiencies have also been observed; 2) alveolar proteinosis, characterized by the storage of a mixed, protein and lipid material, and which constitutes a relatively heterogeneous clinical biological syndrome, with regards to age at onset (from the neonate through to adulthood) as well as the severity of associated signs. Murine models with a targeted mutation of the gene encoding GM-CSF (Csfgm) or the beta subunit of its receptor (Il3rbl) support the hypothesis of an abnormality of surfactant turnover in which the alveolar macrophage would be a key player. Beside SP-B deficiency, in which a near-consensus diagnostic chart can be designed, the ascertainment of other abnormalities of surfactant metabolism is not straightforward. The disentanglement of this disease cluster is however essential, with aim to propose differentiated therapeutic procedure : repeated bronchoalveolar lavages, GM-CSF replacement, bone marrow grafting or lung transplantation.
Service de biochimie et biologie moléculaire, Hôpital d'enfants Armand-Trousseau, 26, avenue du Docteur-Arnold-Netter, 75571 Paris cedex 12.
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Tredano
J D
JD
Blic
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Griese
J C
JC
Fournet
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Elion
M
M
Bahuau
D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D000818:Animals; D001706:Biopsy; D016026:Bone Marrow Transplantation; D001992:Bronchoalveolar Lavage Fluid; D003937:Diagnosis, Differential; D004195:Disease Models, Animal; D005808:Genes, Recessive / Q000235:genetics; D018740:Genetic Heterogeneity; D005838:Genotype; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000627:therapeutic use; D006801:Humans; D016040:Lung Transplantation; D016676:Macrophages, Alveolar; D051379:Mice; D008967:Molecular Biology; D009154:Mutation / Q000235:genetics; D011510:Proteolipids / Q000737:chemistry / Q000235:genetics*; D011649:Pulmonary Alveolar Proteinosis / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D011663:Pulmonary Surfactants / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics*
D011510:Proteolipids; D011663:Pulmonary Surfactants; D016178:Granulocyte-Macrophage Colony-Stimulating Factor