Clinical Significance of Serum Anti-GM-CSF Autoantibody Levels in Autoimmune Pulmonary Alveolar Proteinosis

Nakagawa, Masaki; Yamaguchi, Etsuro; Takahashi, A; Asai, Nobuhiro; Katsuda, Eisuke; Ohta, Tatsuro; Ohtsuka, Yoshinori; Kosaka, Kenshi; Matsubara, Ayako; Tanaka, Hiroyuki; Yokoe, Norihito; Kubo, Akihito; Konno, Satoshi; Baba, Kenji

doi:10.2217/bmm-2017-0362

Cited by 14 publications

(14 citation statements)

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“…Recently, Nakata et al validated a new serum GMAb testing kit and provided an optimal cut-off value for these individuals [29]. Several studies have evaluated GMAb levels in other lung diseases [5,8,20]. Nishimura et al demonstrated the cut-off serum GMAb values measured by ELISA to discriminate aPAP from healthy controls or other lung diseases as 2.0 μg/mL (sensitivity 100%, specificity 100%) or 2.8 μg/mL (sensitivity 100%, specificity 98%) [20].…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have evaluated GMAb levels in other lung diseases [5,8,20]. Nishimura et al demonstrated the cut-off serum GMAb values measured by ELISA to discriminate aPAP from healthy controls or other lung diseases as 2.0 μg/mL (sensitivity 100%, specificity 100%) or 2.8 μg/mL (sensitivity 100%, specificity 98%) [20]. They reported that GMAb levels in sarcoidosis and pneumoconiosis patients were slightly higher than those in healthy controls [20].…”

Section: Discussionmentioning

confidence: 99%

“…There are several reports on GMAb cut-off values for aPAP diagnosis. Using polyclonal GMAb as the standard, Nishimura et al [ 20 ] and Nakata et al [ 29 ] reported cut-off values of 2.8 µg/mL and 1.0 µg/mL for GMAb, respectively. By comparison, using monoclonal GMAb as the standard, we reported a cut-off value of 0.5 µg/mL [ 2 ], whereas Uchida et al considered 5.0 µg/mL as the cut-off value [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

“…Verma et al described five patients with histopathological features of both PAP and HP [19]. Nishimura et al [20] reported that serum GMAb levels were slightly elevated in sarcoidosis patients compared with healthy controls. Relatively elevated-GMAb levels in granulomatous lung diseases such as sarcoidosis or HP may exist, but the incidence and clinical features of this condition are unknown.…”

Section: Introductionmentioning

confidence: 99%

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Clinical significance of serum anti-granulocyte–macrophage colony-stimulating factor autoantibodies in patients with sarcoidosis and hypersensitivity pneumonitis

Katayama

Hirose

Arai

et al. 2020

Orphanet J Rare Dis

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Background Anti-granulocyte–macrophage colony-stimulating factor autoantibody (GMAb) has been recognized as a diagnostic biomarker for autoimmune pulmonary alveolar proteinosis (aPAP). The aims of this study were to know the incidence of increased level of serum GMAb in granulomatous lung diseases (sarcoidosis and hypersensitivity pneumonitis [HP]) and to clarify the role of GMAb. Consecutive individuals diagnosed with sarcoidosis (n = 92) and HP (n = 45) at National Hospital Organization Kinki-Chuo Chest Medical Center were retrospectively analyzed. We measured serum GMAb levels at the diagnosis. Cut-off values of GMAb discriminating aPAP (n = 110) from healthy controls (n = 31) were determined by receiver operating characteristic (ROC) curve analysis. We compared the clinical features of sarcoidosis and HP patients with GMAb levels above the cut-off value (“Elevated-GMAb”) with those of patients whose GMAb levels below the cut-off value (“Low-GMAb”). Radiological and pathological findings in elevated-GMAb patients were re-evaluated to elucidate the role of GMAb in granulomatous lung diseases. Results Analysis of ROC indicated a sensitivity and specificity of 100% at GMAb level of 3.33 μg/mL for discriminating aPAP from healthy controls (area under curve = 1.000, p < 0.0001). The percentages of elevated-GMAb sarcoidosis and HP patients were 5.4% (n = 5) and 11.1% (n = 5), respectively. The number of comorbid sarcoidosis and HP patients with aPAP was two and one, respectively. Elevated-GMAb sarcoidosis patients presented with significantly higher serum levels of Krebs von den Lungen (KL)-6, surfactant protein-D (SP-D), lactate dehydrogenase, and the requirement of systemic corticosteroid therapy. Elevated-GMAb HP patients demonstrated older age, higher serum KL-6, SP-D, carcinoembryonic antigen, and cytokeratin fragment 21-1 levels, and a higher percentage of lymphocytes in bronchoalveolar lavage than low-GMAb patients. A subset of patients presented with radiological and pathological findings characteristic of aPAP. Conclusions We demonstrated the percentage of elevated-GMAb sarcoidosis and HP patients who presented with several features suggestive of aPAP. Elevated-GMAb sarcoidosis and HP patients without definitive aPAP diagnosis may have subclinical or early-stage aPAP and may not necessarily indicate false positives. Upon diagnosis of sarcoidosis or HP, measurement of GMAb may be useful in detecting possible comorbidity of subclinical or early-onset aPAP.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Clinical significance of serum anti-granulocyte–macrophage colony-stimulating factor autoantibodies in patients with sarcoidosis and hypersensitivity pneumonitis

Katayama

Hirose

Arai

et al. 2020

Orphanet J Rare Dis

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“…Another report of dust-related PAP with anti-GM-CSF antibody discussed a case caused by occupational exposure to indium-tin oxide for 4 months (12). Additionally, anti-GM-CSF antibodies were reported to be positive in many patients with pneumoconiosis who merged PAP (13). However, there are no reports on PAP with anti-GM-CSF antibody detected after one-time exposure to dust.…”

Section: Discussionmentioning

confidence: 99%

Autoimmune Pulmonary Alveolar Proteinosis Diagnosed after Exposure to a Fire Extinguisher Containing Silica Powder

et al. 2019

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We herein report a case of autoimmune pulmonary alveolar proteinosis (PAP) diagnosed after one-time exposure to silica powder. Owing to the misuse of a silica-containing fire extinguisher and the inhalation of large amounts of its powder, the patient experienced prolonged cough and visited our hospital. The findings of chest computed tomography and surgical lung biopsy specimens led to the diagnosis of PAP. Interestingly, the presence of anti-GM-CSF antibody was detected; therefore, both autoimmune characteristics and exposure to large amounts of silica may have caused the development of PAP in this patient. This case provides important insight into the mechanisms leading to the onset of PAP.

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Genetic determinants of risk in autoimmune pulmonary alveolar proteinosis

et al. 2021

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Pulmonary alveolar proteinosis (PAP) is a devastating lung disease caused by abnormal surfactant homeostasis, with a prevalence of 6–7 cases per million population worldwide. While mutations causing hereditary PAP have been reported, the genetic basis contributing to autoimmune PAP (aPAP) has not been thoroughly investigated. Here, we conducted a genome-wide association study of aPAP in 198 patients and 395 control participants of Japanese ancestry. The common genetic variant, rs138024423 at 6p21, in the major-histocompatibility-complex (MHC) region was significantly associated with disease risk (Odds ratio [OR] = 5.2; P = 2.4 × 10−12). HLA fine-mapping revealed that the common HLA class II allele, HLA-DRB1*08:03, strongly drove this signal (OR = 4.8; P = 4.8 × 10−12), followed by an additional independent risk allele at HLA-DPβ1 amino acid position 8 (OR = 0.28; P = 3.4 × 10−7). HLA-DRB1*08:03 was also associated with an increased level of anti-GM-CSF antibody, a key driver of the disease (β = 0.32; P = 0.035). Our study demonstrated a heritable component of aPAP, suggesting an underlying genetic predisposition toward an abnormal antibody production.

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Clinical Significance of Serum Anti-GM-CSF Autoantibody Levels in Autoimmune Pulmonary Alveolar Proteinosis

Abstract: Our results indicate the existence of threshold levels of serum anti-GM-CSF IgG for the development and persistence of aPAP.

Cited by 14 publications

References 13 publications

Clinical significance of serum anti-granulocyte–macrophage colony-stimulating factor autoantibodies in patients with sarcoidosis and hypersensitivity pneumonitis

Clinical significance of serum anti-granulocyte–macrophage colony-stimulating factor autoantibodies in patients with sarcoidosis and hypersensitivity pneumonitis

Autoimmune Pulmonary Alveolar Proteinosis Diagnosed after Exposure to a Fire Extinguisher Containing Silica Powder

Genetic determinants of risk in autoimmune pulmonary alveolar proteinosis

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