Autoimmune Pulmonary Alveolar Proteinosis Research Articles

Nocardia infection in patients with anti-GM-CSF autoantibodies: a prospective multicenter French study

Abstract Background Nocardiosis, a bacterial opportunistic infection caused by Nocardia spp., has recently been reported in patients with anti-Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF) autoantibodies but insufficient data are available about disease presentation, outcomes, and occurrence of autoimmune pulmonary alveolar proteinosis (aPAP) in this population. Methods We performed a prospective, multicenter, nationwide study in France and included patients with a Nocardia infection who had anti-GM-CSF autoantibodies. We describe their clinical, microbiological, and radiological characteristics, and their outcome at 1 year of follow-up. Results Twenty patients were included, 18 (90%) men, median age 69 [44-75] years. The organs most frequently involved were the brain (14/20; 70%) and the lung (12/20; 60%). Half of the infections were disseminated (10/20; 50%). Nocardia identification was predominantly made in abscess fluid (17/20; 85%) among which 10 (59%) were brain abscesses. The one-year all-cause mortality was 5% (1/20) and only one case of aPAP (1/20; 5%) occurred during the follow-up period. Conclusions Nocardiosis with anti-GM-CSF autoantibodies is associated with a low mortality rate despite a high incidence of brain involvement. Although the occurrence of aPAP was infrequent during the one-year follow-up period, long-term clinical data are needed to fully understand the potential relationship between nocardiosis, anti-GM-CSF autoantibodies, and aPAP.

A case of autoimmune pulmonary alveolar proteinosis during the course of treatment of rapidly progressive interstitial pneumonia associated with anti-MDA5 antibody-positive dermatomyositis.

Autoimmune pulmonary alveolar proteinosis (APAP) is a diffuse lung disease that causes abnormal accumulation of lipoproteins in the alveoli; however, its pathogenesis remains unclear. Recently, APAP cases have been reported during the course of dermatomyositis. The combination of these two diseases may be coincidental; however, it may have been overlooked because differentiating APAP from a flare-up of interstitial pneumonia associated with dermatomyositis is challenging. This didactic case demonstrates the need for early APAP scrutiny. A 50-year-old woman was diagnosed with anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive dermatitis and interstitial pneumonia in April 2021. The patient was treated with corticosteroids, tacrolimus, and cyclophosphamide pulse therapy for interstitial pneumonia complicated by MDA5 antibody-positive dermatitis, which improved the symptoms and interstitial pneumonia. Eight months after the start of treatment, a new interstitial shadow appeared that worsened. Therefore, three additional courses of cyclophosphamide pulse therapy were administered; however, the respiratory symptoms and interstitial shadows did not improve. Respiratory failure progressed, and 14months after treatment initiation, bronchoscopy revealed turbid alveolar lavage fluid, numerous foamy macrophages, and numerous periodic acid-Schiff-positive unstructured materials. Blood test results revealed high anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody levels, leading to a diagnosis of APAP. The patient underwent whole-lung lavage, and the respiratory disturbance promptly improved. Anti-GM-CSF antibodies were measured from the cryopreserved serum samples collected at the time of diagnosis of anti-MDA5 antibody-positive dermatitis, and 10months later, both values were significantly higher than normal. This is the first report of anti-MDA5 antibody-positive dermatomyositis complicated by interstitial pneumonia with APAP, which may develop during immunosuppressive therapy and be misdiagnosed as a re-exacerbation of interstitial pneumonia. In anti-MDA5 antibody-positive dermatomyositis, APAP comorbidity may have been overlooked, and early evaluation with bronchoalveolar lavage fluid and anti-GM-CSF antibody measurements should be considered, keeping the development of APAP in mind.

Disseminated nocardiosis and anti-GM-CSF antibodies.

Infections that are unusually severe or caused by opportunistic pathogens are a hallmark of primary immunodeficiency (PID). Anti-cytokine autoantibodies (ACA) are an emerging cause of acquired immunodeficiency mimicking PID. Nocardia spp. are Gram-positive bacteria generally inducing disseminated infections in immunocompromised patients, but seldom also occurring in apparently immunocompetent hosts. Anti-GM-CSF autoantibodies are associated with autoimmune pulmonary alveolar proteinosis (PAP). In those patients, an increased incidence of disseminated nocardiosis and cryptococcosis has been observed. It is unclear whether the PAP or the autoantibodies predispose to the infection. We report an apparently immunocompetent woman presenting with disseminated nocardiosis without any evidence of PAP. Clinical data and radiological images were retrospectively collected. Lymphocyte populations were analyzed by flow cytometry. Anti-GM-CSF autoantibodies were measured by ELISA. A 55-year-old otherwise healthy woman presented with cerebral and pulmonary abscesses. Personal and familial history of infections or autoimmunity were negative. After extensive examinations, a final diagnosis of disseminated nocardiosis was made. Immunologic investigations including neutrophilic function and IFN-γ/IL-12 circuitry failed to identify a PID. Whole-exome sequencing did not find pathogenic variants associated with immunodeficiency. Serum anti-GM-CSF autoantibodies were positive. There were no clinical or instrumental signs of PAP. Trimethoprim-sulfamethoxazole and imipenem were administered, with progressive improvement and recovery of the infectious complication. We identified anti-GM-CSF autoantibodies as the cause of disseminated nocardiosis in a previously healthy and apparently immunocompetent adult. This case emphasizes the importance of including ACA in the differential diagnosis of PID, especially in previously healthy adults. Importantly, anti-GM-CSF autoantibodies can present with disseminated nocardiosis without PAP.

February 2024 Medical Image of the Month: Pulmonary Alveolar Proteinosis in Myelodysplastic Syndrome

No abstract available. Manuscript truncated after 150 words. Lymphadenopathy decreased after initiation of coccidiomycosis treatment, but symptoms and crazy paving findings continued to worsen. Further workup revealed a new diagnosis of myelodysplastic syndrome (MDS) and subsequent bronchoalveolar lavage (BAL) and histology results were consistent with secondary PAP, likely due to patient’s underlying hematologic disease. Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by the accumulation of lipoproteinaceous material in the lung alveoli. There are two types of PAP that occur in adults: Idiopathic/ autoimmune and Secondary PAP. Idiopathic/autoimmune PAP is more common and is thought to result from antibody production against granulocyte-macrophage-colony-stimulating factor (GM-CSF) that regulates surfactant homeostasis. Secondary PAP results from a precipitating condition, often inhalation exposure, underlying malignancy, or immunocompromise. The clinical manifestations of PAP are nonspecific and includes dyspnea, nonproductive cough, fatigue, and weight loss. CT may show nonspecific findings of smooth, bilateral interlobular septal thickening superimposed on a background of ground-glass opacification (crazy-paving). Diagnosis is confirmed with …

ЛЕГЕНЕВИЙ АЛЬВЕОЛЯРНИЙ ПРОТЕЇНОЗ: ВИПАДОК СУБТОТАЛЬНОГО УРАЖЕННЯ ПАРЕНХІМИ ЛЕГЕНЬ)

Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disease, characterized by the intraalveolar accumulation of surfactant-like lipoprotein substance. There are three forms of the disease: autoimmune (formerly known as idiopathic), secondary and congenital PAP. The disturbances of surfactant metabolism (protein-lipoid complex secreted by type II pneumocytes) play the crucial role in the development of the disease. Surfactant decreases a surface tension of alveoli and prevents its collapse at the end of the expiration and takes part in protection against infections as well. Surfactant is inactivated through the transformation into the surface-inactive aggregates, which are mainly absorbed by type II pneumocytes. The rest of surfactant are catabolized by alveolar macrophages (AM). This process is regulated by cytokines, especially granulocyte-macrophage colony-stimulating factor (GM-CSF) being the most important of them. Disturbances of interrelation between GM-CSF and cellular receptors blocks the signals to effector cells for surfactant deactivation. This is resulted in excessive accumulation of surfactant in alveoli. General lavage of the lung is a standard method of symptomatic management of PAP. Contemporary pathogenesis treatment uses two approaches — increasing the clearance of surfactant by means of exogenous GM-CSF administration and decreasing the level of GM-CSF antibodies using the rituximab and plasmapheresis. Due to the use of broncho-alveolar lavage (BAL) 5-year survival rate of th patients reaches 95 %. The mortality depends on the area of lung lesion and reversely correlated with the timely diagnosis and treatment. We report the case of subtotal lung parenchyma lesion associated with severe respiratory failure in 46 years old patient. Three series of BAL (5 procedures in each with 1-2 months interval) were performed using the limited volume of lavage fluid due to the severity of the patient’s condition. The results was an improvement of clinical condition, resolution of respiratory failure, significant reduction of the size of the lesions, improved lung transparency on CT scan, restoration of lung diffusion and total lung capacity. Conclusion. Therapeutic BAL is an effective method of PAP management. The outcome of clinical case presented and our many years experience confirm not only the effectiveness of conventional BAL with reduced lavage volume application but also a safety of fiberoptic bronchoscopy, especially in patients with subtotal involvement of lung parenchyma. Key words: pulmonary alveolar proteinosis, subtotal pulmonary parenchyma involvement, pulmonary bronchoalveolar lavage, efficiency.

Nebulised granulocyte-macrophage colony-stimulating factor (GM-CSF) in autoimmune pulmonary alveolar proteinosis: a systematic review and meta-analysis.

Autoimmune pulmonary alveolar proteinosis (aPAP) results from impaired macrophage-mediated clearance of alveolar surfactant lipoproteins. Whole lung lavage has been the first-line treatment but recent reports suggest the efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF). We aimed to review the efficacy and safety of nebulised GM-CSF in aPAP. We conducted a systematic review and meta-analysis searching Embase, CINAHL, MEDLINE and Cochrane Collaborative databases (1946-1 April 2022). Studies included patients aged >18 years with aPAP receiving nebulised GM-CSF treatment and a comparator cohort. Exclusion criteria included secondary or congenital pulmonary alveolar proteinosis, GM-CSF allergy, active infection or other serious medical conditions. The protocol was prospectively registered with PROSPERO (CRD42021231328). Outcomes assessed were St George's Respiratory Questionnaire (SGRQ), 6-min walk test (6MWT), gas exchange (diffusing capacity of the lung for carbon monoxide (D LCO) % predicted) and arterial-alveolar oxygen gradient. Six studies were identified for review and three for meta-analysis, revealing that SGRQ score (mean difference -8.09, 95% CI -11.88- -4.3, p<0.0001), functional capacity (6MWT) (mean difference 21.72 m, 95% CI -2.76-46.19 m, p=0.08), gas diffusion (D LCO % predicted) (mean difference 5.09%, 95% CI 2.05-8.13%, p=0.001) and arterial-alveolar oxygen gradient (mean difference -4.36 mmHg, 95% CI -7.19- -1.52 mmHg, p=0.003) all significantly improved in GM-CSF-treated patients with minor statistical heterogeneity (I2=0%). No serious trial-related adverse events were reported. Patients with aPAP treated with inhaled GM-CSF demonstrated significant improvements in symptoms, dyspnoea scores, lung function, gas exchange and radiology indices after treatment with nebulised GM-CSF of varying duration. There is an important need to review comparative effectiveness and patient choice in key clinical outcomes between the current standard of care, whole lung lavage, with the noninvasive treatment of nebulised GM-CSF in aPAP.

Effects of COVID-19 infection in patients with autoimmune pulmonary alveolar proteinosis: a single-center study

BackgroundAutoimmune pulmonary alveolar proteinosis (aPAP) is a rare interstitial lung disease. COVID-19 is associated with worse prognosis in previous lung diseases patients. But the prognosis of aPAP patients after infection with COVID-19 is unclear. In December 2022, China experienced a large-scale outbreak of Omicron variant of the SARS-CoV-2. In this study, we aim to explore the clinical outcomes of aPAP patients infected with COVID-19.ResultsA total of 39 aPAP patients were included in this study. 30.77% patients had a decrease in oxygen saturation after COVID-19 infection. We compared the two groups of patients with or without decreased oxygen saturation after COVID-19 infection and found that patients who had previous oxygen therapy (decreased oxygen saturation vs. non decreased oxygen saturation: 6/12 vs. 4/27, P = 0.043), with lower baseline arterial oxygen partial pressure (74.50 ± 13.61 mmHg vs. 86.49 ± 11.92 mmHg, P = 0.009), lower baseline DLCO/VA% [77.0 (74.3, 93.6) % vs. 89.5 (78.2, 97.4) %, P = 0.036], shorter baseline 6MWD [464 (406, 538) m vs. 532 (470, 575) m, P = 0.028], higher disease severity score (P = 0.017), were more likely to have decreased oxygen saturation after COVID-19 infection.ConclusionaPAP patients with poor baseline respiration have a higher probability of hypoxia after COVID-19 infection, but fatal events were rare.

Coexistence of Autoimmune Pulmonary Alveolar Proteinosis With Small Cell Lung Cancer in a Man Presenting With Acute Onset Respiratory Failure

Coexistence of Autoimmune Pulmonary Alveolar Proteinosis With Small Cell Lung Cancer in a Man Presenting With Acute Onset Respiratory Failure

HLA-DRB1*14:54 Is Associated with Pulmonary Alveolar Proteinosis: A Retrospective Real-World Audit.

Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disease characterized by abnormal accumulation of pulmonary surfactant lipids in alveoli or terminal bronchioles, leading to increased infection risk and progressive respiratory failure. Approximately more than 90% of all cases are autoimmune PAP (aPAP). Since one of the predisposing factors has been identified as genes located within the major-histocompatibility-complex region, an investigation of human leukocyte antigen (HLA) alleles associated with the risk of aPAP is warranted. We retrospectively studied 60 patients pathologically diagnosed with PAP from 2019 to 2022. Patients were divided into the aPAP group or secondary PAP (sPAP) group according to their clinical information. Qualified DNA was extracted from the paraffin-embedded tissue of 28 patients, and the PCR-sequence-based typing method was used for HLA-DRB1 genotyping. A similar HLA-DRB1 allele profile (including the HLA-DRB1*08:03) between the aPAP group and sPAP group was revealed, except that HLA-DRB1*14:54, which has never been reported in aPAP patients, was only detected in the aPAP group rather than the sPAP group (19.4% vs. 0.0%, p = 0.030). Under inhaled granulocyte-macrophage colony-stimulating factor therapy, more clinical remission was observed in HLA-DRB1*14:54 carriers rather than in HLA-DRB1*08:03 carriers (80.0% vs. 57.1%). Our real-world study revealed for the first time that a population with HLA-DRB1*14:54 was subject to aPAP, and HLA-DRB1*14:54 might imply a response in aPAP patients to inhaled granulocyte-macrophage colony-stimulating factor in aPAP patients.

Infections in autoimmune pulmonary alveolar proteinosis: a large retrospective cohort

BackgroundAutoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease, predisposing to an increased risk of infection. A complete picture of these infections is lacking.Research questionDescribe the characteristics and clinical outcomes...

Altered macrophage phenotypes in a case of autoimmune pulmonary alveolar proteinosis.

Mass cytometry of BALF cells from a pulmonary alveolar proteinosis patient, positive for anti-GM-CSF antibodies, suggests potential impairment in human alveolar macrophage differentiation https://bit.ly/45JHUrz.

Response to inhaled granulocyte-macrophage colony-stimulating factor in patient with mild-to-moderate autoimmune pulmonary alveolar proteinosis-24 months of follow-up.

Autoimmune pulmonary alveolar proteinosis (aPAP) is a disease caused by IgG antibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF). Whole lung lavage (WLL) allows to remove the lipo-proteinaceous material accumulated by the poor clearance of alveolar surfactant. However, it is a complex technique that is not exempt from complications, and in some cases, the patients are refractory, requiring the performance of several WLLs spaced apart in time. We present the clinical, functional, and radiological evolution after 24 months of follow-up of a patient diagnosis of aPAP refractory to WLL, with performed three therapeutic WLLs spaced 16 and 36 months and serious potentially fatal complications in the last one. After 24 months, no adverse effects have appeared and the great clinical, functional and radiological response is maintained. The patient has beensuccessfully treated with inhaled recombinant human GM-CSF sargramostim.

A Rare Case of Autoimmune Pulmonary Alveolar Proteinosis Complicated with Pulmonary Tuberculosis — a Case Report

A Rare Case of Autoimmune Pulmonary Alveolar Proteinosis Complicated with Pulmonary Tuberculosis — a Case Report

A Case of Autoimmune Pulmonary Alveolar Proteinosis with Suspected Exacerbation after Osimertinib Administration for Lung Cancer.

A 46-year-old woman with lung cancer who received chemotherapy was admitted to our hospital for lower-lobe bilateral ground-glass opacity (GGO). GGO developed after the lung cancer diagnosis, deteriorated after the initiation of osimertinib, and incompletely decreased after interrupting osimertinib; therefore, flexible bronchoscopy was performed. Transbronchial lung biopsy histology and anti-granulocyte/macrophage colony-stimulating factor autoantibody positivity revealed autoimmune pulmonary alveolar proteinosis (aPAP) that did not require treatment. This rare case of aPAP comorbid with lung cancer suggested that using PAP findings to differentiate from drug-induced lung injury or lymphangitis is difficult and that osimertinib was suspected to exacerbate aPAP.

Updated severity and prognosis score of pulmonary alveolar proteinosis: A multi-center cohort study in China.

The high-resolution computed tomography (HRCT) score is an important component of the severity and prognosis score of pulmonary alveolar proteinosis (SPSP). However, the HRCT score in SPSP only considers the extent of opacity, which is insufficient. We retrospectively evaluated HRCT scores for 231 patients with autoimmune pulmonary alveolar proteinosis (APAP) from three centers of the China Alliance for Rare Diseases. The SPSPII was created based on the overall density and extent, incorporating the SPSP. The severity of APAP patients was assessed using disease severity scores (DSS), SPSP, and SPSPII to determine the strengths and weaknesses of the different assessment methods. We then prospectively applied the SPSPII to patients before treatment, and the curative effect was assessed after 3 months. The HRCT overall density and extent scores in our retrospective analysis were higher than the extent scores in all patients and every original extent score severity group, as well as higher related to arterial partial oxygen pressure (PaO2) than extent scores. The mild patients accounted for 61.9% based on DSS 1-2, 20.3% based on SPSP 1-3, and 20.8% based on SPSPII 1-3. Based on SPSP or SPSPII, the number of severe patients deteriorating was higher in the mild and moderate groups. When applied prospectively, arterial PaO2 differed between any two SPSPII severity groups. The alveolar-arterial gradient in PaO2 (P[A-a]O2), % predicted carbon monoxide diffusing capacity of the lung (DLCO), and HRCT score were higher in the severe group than in the mild and moderate groups. After diagnosis, mild patients received symptomatic treatment, moderate patients received pure whole lung lavage (WLL) or granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy, and severe patients received WLL and GM-CSF therapy. Importantly, the SPSPII in mild and severe groups were lower than baseline after 3 months. The HRCT density and extent scores of patients with APAP were better than the extent score. The SPSPII score system based on smoking status, symptoms, PaO2, predicted DLCO, and overall HRCT score was better than DSS and SPSP for assessing the severity and efficacy and predicting the prognosis. ClinicalTrial.gov, identifier: NCT04516577.

Autoimmune Pulmonary Alveolar Proteinosis during the Treatment of Idiopathic Inflammatory Myopathy.

Approximately 50% of idiopathic inflammatory myopathies (IIMs) are associated with interstitial lung disease (ILD). Typically, IIM-ILD manifests as nonspecific interstitial pneumonia. We herein report a rare case of a 78-year-old man with autoimmune pulmonary alveolar proteinosis (PAP) that developed during IIM treatment. The diagnosis of autoimmune PAP was based on detecting anti-granulocyte-macrophage colony-stimulating factor antibodies. We postulated that PAP may have been induced by IIM treatment with prednisolone. Our case suggests that the possibility of autoimmune PAP should be considered in patients with lung lesions during the clinical course of IIM.

Recombinant GM-CSF for diseases of GM-CSF insufficiency: Correcting dysfunctional mononuclear phagocyte disorders.

Endogenous granulocyte-macrophage colony-stimulating factor (GM-CSF), identified by its ability to support differentiation of hematopoietic cells into several types of myeloid cells, is now known to support maturation and maintain the metabolic capacity of mononuclear phagocytes including monocytes, macrophages, and dendritic cells. These cells sense and attack potential pathogens, present antigens to adaptive immune cells, and recruit other immune cells. Recombinant human (rhu) GM-CSF (e.g., sargramostim [glycosylated, yeast-derived rhu GM-CSF]) has immune modulating properties and can restore the normal function of mononuclear phagocytes rendered dysfunctional by deficient or insufficient endogenous GM-CSF. We reviewed the emerging biologic and cellular effects of GM-CSF. Experts in clinical disease areas caused by deficient or insufficient endogenous GM-CSF examined the role of GM-CSF in mononuclear phagocyte disorders including autoimmune pulmonary alveolar proteinosis (aPAP), diverse infections (including COVID-19), wound healing, and anti-cancer immune checkpoint inhibitor therapy. We discuss emerging data for GM-CSF biology including the positive effects on mitochondrial function and cell metabolism, augmentation of phagocytosis and efferocytosis, and immune cell modulation. We further address how giving exogenous rhu GM-CSF may control or treat mononuclear phagocyte dysfunction disorders caused or exacerbated by GM-CSF deficiency or insufficiency. We discuss how rhu GM-CSF may augment the anti-cancer effects of immune checkpoint inhibitor immunotherapy as well as ameliorate immune-related adverse events. We identify research gaps, opportunities, and the concept that rhu GM-CSF, by supporting and restoring the metabolic capacity and function of mononuclear phagocytes, can have significant therapeutic effects. rhu GM-CSF (e.g., sargramostim) might ameliorate multiple diseases of GM-CSF deficiency or insufficiency and address a high unmet medical need.

Pulmonary Alveolar Proteinosis: An Overview and Emerging Therapeutics

Pulmonary alveolar proteinosis (PAP) is a rare pulmonary syndrome characterized by surfactant accumulation in the alveoli, which results in impaired gas exchange. There are three types of PAP: primary, secondary and congenital. Autoimmune PAP, which is under the category of primary PAP, is the most common form, and is caused by an impairment in granulocyte–macrophage colony-stimulating factor (GM-CSF) signalling, due to the presence of anti-GM-CSF autoantibodies. While some patients with PAP remain asymptomatic, most present with progressive dyspnoea of insidious onset that, rarely, can progress to respiratory failure and death. Currently, there is no known cure and no approved therapies for PAP. Whole-lung lavage remains the gold-standard treatment; however, several novel and promising targeted therapies are being actively investigated.

Quantitative Evaluation of Changes in Three-Dimensional CT Density Distributions in Pulmonary Alveolar Proteinosis after GM-CSF Inhalation

Background: A previous clinical trial for autoimmune pulmonary alveolar proteinosis (APAP) demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) inhalation reduced the mean density of the lung field on computed tomography (CT) across 18 axial slice planes at a two-dimensional level. In contrast, in this study, we challenged three-dimensional analysis for changes in CT density distribution using the same datasets. Methods: As a sub-study of the trial, CT data of 31 and 27 patients who received GM-CSF and placebo, respectively, were analyzed. To overcome the difference between various shooting conditions, a newly developed automatic lung field segmentation algorithm was applied to CT data to extract the whole lung volume, and the accuracy of the segmentation was evaluated by five pulmonary physicians independently. For normalization, the percent pixel (PP) in a certain density range was calculated as a percentage of the total number of pixels from −1,000 to 0 HU. Results: The automatically segmented images revealed that the lung field was accurately extracted except for 7 patients with minor deletion or addition. Using the change in PP from baseline to week 25 (ΔPP) as the vertical axis, we created a histogram with 143 HU bins set for each patient. The most significant difference in ΔPP between GM-CSF and placebo groups was observed in two ranges: from −1,000 to −857 and −143 to 0 HU. Conclusion: Whole lung extraction followed by density histogram analysis of ΔPP may be an appropriate evaluation method for assessing CT improvement in APAP.

A dried blood spot test for diagnosis of autoimmune pulmonary alveolar proteinosis

Granulocyte/macrophage colony-stimulating factor autoantibodies (GMAbs) mediate the pathogenesis of autoimmune pulmonary alveolar proteinosis (autoimmune PAP) and their quantification in serum by enzyme-linked immunosorbent assay (ELISA) – the serum GMAb test – is the ‘gold standard’ for diagnosis of autoimmune PAP. Because GMAbs are high in autoimmune PAP and low or undetectable in healthy people, we hypothesized that the ELISA could be adapted for evaluation of blood obtained from the fingertip using a dried blood spot card (DBSC) for specimen collection. Here, we report development of such a method – the DBSC GMAb test – and evaluate its ability to measure GMAb concentration in blood and to diagnose autoimmune PAP. Fresh, heparinized whole blood was obtained from 60 autoimmune PAP patients and 19 healthy people and used to measure the GMAb concentration in blood (by the DBSC GMAb test). After optimization, the DBSC GMAb test was evaluated for accuracy, precision, reliability, sensitivity, specificity, and ruggedness. The coefficient of variation among repeated measurements was low with regard to well-to-well, plate-to-plate, day-to-day, and inter-operator variation, and results were unaffected by exposure of prepared DBSC specimens to a wide range of temperatures (from -80 °C to 65 °C), repeated freeze-thaw cycles, or storage for up to 2.5 months before testing. The limit of blank (LoB), limit of detection (LoD), and lower limit of quantification (LLoQ), were 0.01, 0.21, and 3.5 μg/ml of GMAb in the blood, respectively. Receiver operating curve characteristic analysis identified 2.7 μg/ml as the optimal GMAb concentration cutoff value to distinguish autoimmune PAP from healthy people. This cutoff value was less than the LLoQ and the ranges of GMAb results for autoimmune PAP patients and healthy people were widely separated (median (interquartile range): 22.6 (13.3–43.8) and 0.23 (0.20–0.30) μg/ml, respectively). Consequently, the LLoQ is recommended as the lower limit of the range indicating a positive test result (i.e., that autoimmune PAP is present); lower values indicate a negative test result (i.e., autoimmune PAP is not present). Among the 30 autoimmune PAP patients and 19 healthy people evaluated, the sensitivity and specificity of the DBSC GMAb test were both 100% for a diagnosis of autoimmune PAP. Results demonstrate the DBSC GMAb test reliably measures GMAbs in blood and performs well in the diagnosis of autoimmune PAP.