Relationship of anti-GM-CSF antibody concentration, surfactant protein A and B levels, and serum LDH to pulmonary parameters and response to GM-CSF therapy in patients with idiopathic alveolar proteinosis.
BACKGROUND
Conventional measures of the severity of alveolar proteinosis (AP) include alveolar-arterial oxygen gradient ([A - a]DO(2)), vital capacity (VC), and carbon monoxide transfer factor (TLCO), but alternative serological measures have been sought. Granulocyte-macrophage colony stimulating factor (GM-CSF) neutralising autoantibody is found in patients with idiopathic acquired AP. We have investigated the interrelationships between the levels of this antibody and those of surfactant protein (SP)-A and -B, lactate dehydrogenase (LDH), and conventional measures of disease severity, and the capacity of these parameters to predict the response to rhGM-CSF treatment.


METHODS
Blood levels of anti-GM-CSF antibodies, SP-A, SP-B, LDH, and [A - a]DO(2), VC, and TLCO were measured before rhGM-CSF treatment and every 2 weeks thereafter in 14 patients with AP.


RESULTS
At baseline, high levels of anti-GM-CSF antibodies and increased SP-A and SP-B levels were seen in all patients, and LDH was raised in 83%. SP-A was highly correlated with [A - a]DO(2), VC, and TLCO (p</=0.02), but other markers were not. Only a normal LDH level was predictive of a response to rhGM-CSF treatment (p=0.03). During treatment a correlation between conventional and serological variables within patients was seen only between SP-A and [A - a]DO(2) (p=0.054), LDH levels and [A - a]DO(2) (p=0.010), and LDH levels and VC (p=0.019).


CONCLUSIONS
Of the serological parameters studied, only SP-A and LDH levels were correlated with conventional measures of disease severity, with LDH most accurately reflecting [A - a]DO(2) and vital capacity. Only a normal LDH level predicted a higher likelihood of response to treatment with GM-CSF.
Seymour
J F
JF
Melbourne Tumour Biology Branch, Ludwig Institute for Cancer Research, Melbourne, Australia. jseymour@petermac.unimelb.edu.au
Doyle
I R
IR
Nakata
K
K
Presneill
J J
JJ
Schoch
O D
OD
Hamano
E
E
Uchida
K
K
Fisher
R
R
Dunn
A R
AR
D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood* / Q000627:therapeutic use; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood*; D011510:Proteolipids / Q000097:blood*; D011649:Pulmonary Alveolar Proteinosis / Q000097:blood* / Q000188:drug therapy; D037662:Pulmonary Surfactant-Associated Protein A / Q000097:blood*; D011994:Recombinant Proteins
D001323:Autoantibodies; D007074:Immunoglobulin G; D011498:Protein Precursors; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D011994:Recombinant Proteins; C105511:surfactant protein B propeptide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007770:L-Lactate Dehydrogenase