GM-CSF and GM-CSF beta c receptor in adult patients with pulmonary alveolar proteinosis

Pulmonary alveolar proteinosis (PAP) is a rare disorder of unknown origin c haracterized by alveolar fillings with periodic acid-Schiff (PAS)-positive material mainly consisting of phospholipids. Mice defective in the granuloc yte-macrophage colony-stimulating factor (GM-CSF) gene or the GM-CSF/interl eukin (IL)-3/IL-5-receptor common beta chain (beta c) demonstrate a patholo gy resembling PAP. A recent study revealed defects in the beta c chain of t he GM-CSF receptor in four out of eight paediatric patients. This study inv estigates the role of the GM-CSF coding region and components of the GM-CSF receptor in adult patients. Four adult patients with proven PAP were analysed for GM-CSF and GM-CSF-bet a c receptor in regard to protein level, messenger ribonucleic acid (mRNA) expression and sequence composition. None of the adult patients displayed the mutation at position 1,835 of the beta c-receptor previously described in paediatric patients. Expression of the beta c receptor,vas found to be normal on the surface of peripheral blo od cells. In three out of four patients GM-CSF release from blood cells fai led to respond adequately to lipopolysaccharide (LPS). In one of these pati ents a heterozygous mutation was found in the GM-CSF complementary deoxyrib onucleic acid (cDNA) from thymine (T) to cytosine (C) at position 382 df th e published sequence putatively causing a change in the protein from isoleu cine to threonine at position 117. This study indicates that the mutation of the beta chain receptors found in some of the paediatric patients suffering from pulmonary alveolar proteino sis is not a common problem in adult patients.