Molecular and phenotypic variability in the congenital alveolar proteinosis syndrome associated with inherited surfactant protein B deficiency☆,☆☆,★,★★
Section snippets
CASE REPORTS
The study population consisted of seven infants from six unrelated families with biopsy- or autopsy-proven alveolar proteinosis. Salient clinical features of the infants are indicated in Table I. Roman numerals indicate infants from different families. The index family, previously described,11, 13 has been designated as family I; patients IIa, IIb, and III were reported previously.7, 8 The remaining patients were referred to us for surfactant protein analysis because of their clinical disorder.
METHODS
In all cases a portion of the lung tissue was fixed in 10% formaldehyde, dehydrated, and embedded in paraffin. Paraffin sections were stained with hematoxylin and eosin. Additional paraffin sections, 5 μm in thickness, were obtained on Fisher brand Super Frost/Plus microscope slides (Erie Scientific Co., Portsmouth, N.H.), and immunostaining for SP-A, SP-B, and SP-C was done as described previously.15 The intensity and distribution of the immunoreactivity was graded on a scale of 0 to 4 as
Histopathologic findings
The lungs of all patients with CAP had an appearance similar to that described previously for patient Ia—the alveoli were filled with eosinophilic granular material admixed with desquamated type II cells and macrophages. Alveolar lining cells were prominent and there was interstitial fibrosis that produced thickened airspace septa11 (Fig. 1). Lungs of control subjects (not shown) lacked the alveolar granular material but several lungs did contain detached alveolar lining cells within airspaces.
DISCUSSION
Pulmonary surfactant is a lipoprotein complex that reduces surface tension at the air-liquid interface in the alveolus.23, 24 Four surfactant-associated proteins have been characterized to date.25 Surfactant proteins B and C are hydrophobic proteins known to enhance the rate of adsorption of phospholipids to the surface monolayer. Surfactant protein B, along with the hydrophilic protein SP-A, participates in the formation of tubular myelin,26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39
ADDENDUM
Since the submission of this article, patient VI died at 12 months of age.
We thank David Phelps, PhD, for providing the antibodies to SP-A and SP-B, and Jeffrey Whitsett, MD, for providing the antibody to SP-C.
References (46)
- et al.
Congenital pulmonary alveolar proteinosis: failure of treatment with extracorporeal life support
J PEDIATR
(1992) - et al.
What's new in light and electron microscopic immunocytochemistry? Application of the Protein-A gold technique to routinely processed tissue
Pathol Res Pract
(1985) - et al.
Surfactant protein C precursor is palmitoylated and associates with subcellular membranes
Biochim Biophys Acta
(1992) - et al.
Lamellar bodies of cultured human fetal lung: content of surfactant protein A (SP-A), surface film formation and structural transformation in vitro
Biochim Biophys Acta
(1990) - et al.
Proteolipid in bovine lung surfactant: its role in surfactant function
Biochem Biophys Res Commun
(1986) - et al.
Biophysical activity of synthetic phospholipids combined with purified lung surfactant 6,000 dalton apoprotein
Chem Phys Lipids
(1987) Lung surfactant
Biochim Biophys Acta
(1974)- et al.
Role of calcium ions in the structure and function of pulmonary surfactant
Biochim Biophys Acta
(1984) Treatment of congenital alveolar proteinosis [Letter]
J PEDIATR
(1993)- et al.
Pulmonary alveolar proteinosis
N Engl J Med
(1958)
Interstitial plasma cell pneumonia in infnats
Ann Pediatr (Paris)
Pneumocystis carinii pneumonia in an infant
Am J Clin Pathol
Pneumocystis pneumonitis in American infants: report of two cases with autopsy studies
Am J Clin Pathol
Thymic alymphoplasia
Arch Dis Child
Pulmonary alveolar proteinosis in four siblings
N Engl J Med
Pulmonary alveolar proteinosis in a newborn
Pediatr Pulmonol
Pulmonary alveolar proteinosis in the newborn
Arch Pathol Lab Med
Pulmonary alveolar proteinosis: an uncommon cause of chronic neonatal respiratory distress
Am Rev Respir Dis
Deficiency of pulmonary surfactant protein B in congenital alveolar proteinosis
N Engl J Med
Immunogenicity of surfactant II. Porcine and bovine surfactants
Clin Exp Immunol
A mutation in the surfactant protein B gene as the basis for a fatal neonatal respiratory disease in multiple kindreds
J Clin Invest
Expression of the 35 kDa and low molecular weight surfactant associated proteins in the lungs of infants dying with respiratory distress syndrome
Am J Pathol
Cited by (0)
- ☆
From the Departments of Pathology and Pediatrics, St. Louis University, St. Louis, Missouri; Johns Hopkins University, Baltimore, Maryland; University of California, San Diego and Children's Hospital—San Diego; University of California, Davis Medical Center; Children's Hospital, Los Angeles; Northwestern University, Chicago, Illinois; University of Washington, Seattle; University of Michigan, Ann Arbor; and Washington University, St. Louis
- ☆☆
Supported in part by grants from the National Institutes of Health No. HL34748 (Dr. deMello), No. 37591 (Dr. Colten), the American Lung Association, the Fleur de Lis Foundation (Dr. deMello), and the March of Dimes (Dr. Nogee).
- ★
Reprint requests: Daphne E. deMello, MD, Department of Pathology, 1465 S. Grand Blvd., St. Louis, MO 63104.
- ★★
0022-3476/94/$3.00 + 0 9/20/55235