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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
  1. J F Seymour1,2,
  2. I R Doyle4,
  3. K Nakata7,
  4. J J Presneill3,
  5. O D Schoch6,
  6. E Hamano7,
  7. K Uchida7,
  8. R Fisher5,
  9. A R Dunn1
  1. 1Ludwig Institute for Cancer Research, Melbourne Tumour Biology Branch, Melbourne, Australia
  2. 2Department of Haematology/Medical Oncology, Royal Melbourne Hospital, Melbourne, Australia
  3. 3Intensive Care Unit, Royal Melbourne Hospital
  4. 4Department of Human Physiology, Flinders University, Australia
  5. 5Statistical Centre, Peter MacCallum Cancer Institute, Melbourne, Australia
  6. 6Department of Pulmonary Medicine, University Hospital, Zurich, Switzerland
  7. 7Department of Respiratory Diseases, Research Institute, International Medical Center of Japan, Tokyo, Japan
  1. Correspondence to:
    Dr J F Seymour, Division of Haematology/Medical Oncology, Peter MacCallum Cancer Institute, St Andrew’s Place, East Melbourne, Victoria 3002, Australia;
    jseymour{at}petermac.unimelb.edu.au

Abstract

Background: Conventional measures of the severity of alveolar proteinosis (AP) include alveolar-arterial oxygen gradient ([A – a]Do2), 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]do2, 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]do2, 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]do2 (p=0.054), LDH levels and [A – a]do2 (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]Do2 and vital capacity. Only a normal LDH level predicted a higher likelihood of response to treatment with GM-CSF.

  • pulmonary alveolar proteinosis
  • granulocyte-macrophage colony stimulating factor
  • surfactant protein A
  • surfactant protein B
  • autoantibodies
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Footnotes

  • Supported in part by a National Health and Medical Research Council Postgraduate Research Fellowship (JFS).

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