Pulmonary alveolar proteinosis
ICD-10 J84.0 · ICD-11 CB04.31

Autoimmune PAP with Raised GM-CSF Autoantibodies — When Rituximab Has Not Achieved the Expected Goals

This protocol addresses patients with confirmed autoimmune pulmonary alveolar proteinosis (aPAP) who have raised GM-CSF autoantibody titres and continue to show active or worsening disease after a prior course of Rituximab.

Clinical Scenario

Confirmed aPAP with elevated GM-CSF autoantibody titres is the defining feature of this population. Treatment is indicated when disease remains active or continues to worsen. GM-CSF antibody measurement provides objective, reproducible confirmation of the autoimmune aetiology.

Prior Treatment — Goals Not Reached

Patients in this scenario received Rituximab as the preceding line. Escalation to this protocol is triggered by failure to achieve the expected improvements in alveolar–arterial oxygen gradient, arterial oxygen tension on room air, carbon monoxide diffusing capacity, forced vital capacity, or six-minute walk test distance at the 6–12 month assessment.

Next-Line Approach

For patients reaching this stage, the protocol involves an extracorporeal procedure targeting the circulating autoantibodies responsible for the disease. The full selection criteria, sequencing, and monitoring detail are available in the structured protocol.

Treatment Goals

Success is defined by a measurable reduction in GM-CSF autoantibody titres together with improvements in symptoms, oxygenation, radiological appearance, and lung function.

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References
DOI: 10.1183/20734735.0224-2024

Treatment is indicated in patients with active or worsening disease.

GM-CSF antibody measurement is objective, reproducible and has high accuracy for diagnosing aPAP with a level of 10.2 µg·mL−1 or above the threshold of the individual laboratory references.

We suggest the use of plasmapheresis for patients with confirmed aPAP who remain symptomatic, requiring high flow of supplemental oxygen (≥4 L · min−1) or two or more WLL over a period of a year, despite receiving exogenous GM-CSF and rituximab, or having previously failed these treatments (conditional recommendation, very low certainty).

Plasmapheresis was effective in four cases where symptom, oxygenation, radiological or lung function improvements were described.

Most patients (five of nine) had a reduction in GM-CSF antibody titres after plasmapheresis.

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