Cut‐Offs and Diagnostic Performance of IgG Against Recombinant Aspergillus fumigatus Antigens in Differentiating ABPA From Asthma
ABSTRACT Background The diagnostic cut‐off values for IgG antibodies against recombinant Aspergillus fumigatus (rAsp) antigens in allergic bronchopulmonary aspergillosis (ABPA) remain unclear. Objectives To derive and validate diagnostic cut‐offs for IgG antibodies against rAsp f 1, f 2 and f 4 in A...
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| Published in | Mycoses Vol. 68; no. 7; pp. e70087 - n/a |
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| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | English |
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01.07.2025
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| Abstract | ABSTRACT
Background
The diagnostic cut‐off values for IgG antibodies against recombinant Aspergillus fumigatus (rAsp) antigens in allergic bronchopulmonary aspergillosis (ABPA) remain unclear.
Objectives
To derive and validate diagnostic cut‐offs for IgG antibodies against rAsp f 1, f 2 and f 4 in ABPA and assess their diagnostic performance in distinguishing ABPA from asthma.
Methods
In this case‐control study, we prospectively enrolled consecutive subjects with asthma and ABPA. We measured serum IgG levels against rAsp f 1, rAsp f 2 and rAsp f 4 using a fluorescent enzyme immunoassay. Subjects were randomly split into derivation (50%) and validation (50%) cohorts. Cut‐offs were derived using receiver operating characteristic (ROC) curves and Youden's index. Additionally, we performed Bayesian latent class analysis (BLCA) using two‐component Gaussian mixture models to derive unbiased cut‐offs. Diagnostic performance was assessed using sensitivity, specificity and the area under the ROC curve (AUROC).
Results
Of 375 participants, 261 had ABPA and 114 had asthma. ROC‐derived AUROC values for rAsp f 1, f 2 and f 4‐IgG were 0.63, 0.47 and 0.52, while the cut‐off values were 10.1 mgA/L, 10.3 mgA/L and 10.5 mgA/L, respectively. Sensitivity was ≤ 42% for all antigens, while specificity exceeded 89%. BLCA yielded cut‐offs of 18.6, 14.9 and 13.7 mgA/L for f 1, f 2 and f 4, respectively, with similarly poor sensitivity and high specificity.
Conclusions
IgG antibodies against rAsp f 1, f 2 and f 4 exhibit high specificity but poor sensitivity in identifying ABPA, limiting their utility as standalone diagnostic markers. |
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| AbstractList | Background The diagnostic cut‐off values for IgG antibodies against recombinant Aspergillus fumigatus (rAsp) antigens in allergic bronchopulmonary aspergillosis (ABPA) remain unclear. Objectives To derive and validate diagnostic cut‐offs for IgG antibodies against rAsp f 1, f 2 and f 4 in ABPA and assess their diagnostic performance in distinguishing ABPA from asthma. Methods In this case‐control study, we prospectively enrolled consecutive subjects with asthma and ABPA. We measured serum IgG levels against rAsp f 1, rAsp f 2 and rAsp f 4 using a fluorescent enzyme immunoassay. Subjects were randomly split into derivation (50%) and validation (50%) cohorts. Cut‐offs were derived using receiver operating characteristic (ROC) curves and Youden's index. Additionally, we performed Bayesian latent class analysis (BLCA) using two‐component Gaussian mixture models to derive unbiased cut‐offs. Diagnostic performance was assessed using sensitivity, specificity and the area under the ROC curve (AUROC). Results Of 375 participants, 261 had ABPA and 114 had asthma. ROC‐derived AUROC values for rAsp f 1, f 2 and f 4‐IgG were 0.63, 0.47 and 0.52, while the cut‐off values were 10.1 mgA/L, 10.3 mgA/L and 10.5 mgA/L, respectively. Sensitivity was ≤ 42% for all antigens, while specificity exceeded 89%. BLCA yielded cut‐offs of 18.6, 14.9 and 13.7 mgA/L for f 1, f 2 and f 4, respectively, with similarly poor sensitivity and high specificity. Conclusions IgG antibodies against rAsp f 1, f 2 and f 4 exhibit high specificity but poor sensitivity in identifying ABPA, limiting their utility as standalone diagnostic markers. The diagnostic cut-off values for IgG antibodies against recombinant Aspergillus fumigatus (rAsp) antigens in allergic bronchopulmonary aspergillosis (ABPA) remain unclear.BACKGROUNDThe diagnostic cut-off values for IgG antibodies against recombinant Aspergillus fumigatus (rAsp) antigens in allergic bronchopulmonary aspergillosis (ABPA) remain unclear.To derive and validate diagnostic cut-offs for IgG antibodies against rAsp f 1, f 2 and f 4 in ABPA and assess their diagnostic performance in distinguishing ABPA from asthma.OBJECTIVESTo derive and validate diagnostic cut-offs for IgG antibodies against rAsp f 1, f 2 and f 4 in ABPA and assess their diagnostic performance in distinguishing ABPA from asthma.In this case-control study, we prospectively enrolled consecutive subjects with asthma and ABPA. We measured serum IgG levels against rAsp f 1, rAsp f 2 and rAsp f 4 using a fluorescent enzyme immunoassay. Subjects were randomly split into derivation (50%) and validation (50%) cohorts. Cut-offs were derived using receiver operating characteristic (ROC) curves and Youden's index. Additionally, we performed Bayesian latent class analysis (BLCA) using two-component Gaussian mixture models to derive unbiased cut-offs. Diagnostic performance was assessed using sensitivity, specificity and the area under the ROC curve (AUROC).METHODSIn this case-control study, we prospectively enrolled consecutive subjects with asthma and ABPA. We measured serum IgG levels against rAsp f 1, rAsp f 2 and rAsp f 4 using a fluorescent enzyme immunoassay. Subjects were randomly split into derivation (50%) and validation (50%) cohorts. Cut-offs were derived using receiver operating characteristic (ROC) curves and Youden's index. Additionally, we performed Bayesian latent class analysis (BLCA) using two-component Gaussian mixture models to derive unbiased cut-offs. Diagnostic performance was assessed using sensitivity, specificity and the area under the ROC curve (AUROC).Of 375 participants, 261 had ABPA and 114 had asthma. ROC-derived AUROC values for rAsp f 1, f 2 and f 4-IgG were 0.63, 0.47 and 0.52, while the cut-off values were 10.1 mgA/L, 10.3 mgA/L and 10.5 mgA/L, respectively. Sensitivity was ≤ 42% for all antigens, while specificity exceeded 89%. BLCA yielded cut-offs of 18.6, 14.9 and 13.7 mgA/L for f 1, f 2 and f 4, respectively, with similarly poor sensitivity and high specificity.RESULTSOf 375 participants, 261 had ABPA and 114 had asthma. ROC-derived AUROC values for rAsp f 1, f 2 and f 4-IgG were 0.63, 0.47 and 0.52, while the cut-off values were 10.1 mgA/L, 10.3 mgA/L and 10.5 mgA/L, respectively. Sensitivity was ≤ 42% for all antigens, while specificity exceeded 89%. BLCA yielded cut-offs of 18.6, 14.9 and 13.7 mgA/L for f 1, f 2 and f 4, respectively, with similarly poor sensitivity and high specificity.IgG antibodies against rAsp f 1, f 2 and f 4 exhibit high specificity but poor sensitivity in identifying ABPA, limiting their utility as standalone diagnostic markers.CONCLUSIONSIgG antibodies against rAsp f 1, f 2 and f 4 exhibit high specificity but poor sensitivity in identifying ABPA, limiting their utility as standalone diagnostic markers. The diagnostic cut-off values for IgG antibodies against recombinant Aspergillus fumigatus (rAsp) antigens in allergic bronchopulmonary aspergillosis (ABPA) remain unclear. To derive and validate diagnostic cut-offs for IgG antibodies against rAsp f 1, f 2 and f 4 in ABPA and assess their diagnostic performance in distinguishing ABPA from asthma. In this case-control study, we prospectively enrolled consecutive subjects with asthma and ABPA. We measured serum IgG levels against rAsp f 1, rAsp f 2 and rAsp f 4 using a fluorescent enzyme immunoassay. Subjects were randomly split into derivation (50%) and validation (50%) cohorts. Cut-offs were derived using receiver operating characteristic (ROC) curves and Youden's index. Additionally, we performed Bayesian latent class analysis (BLCA) using two-component Gaussian mixture models to derive unbiased cut-offs. Diagnostic performance was assessed using sensitivity, specificity and the area under the ROC curve (AUROC). Of 375 participants, 261 had ABPA and 114 had asthma. ROC-derived AUROC values for rAsp f 1, f 2 and f 4-IgG were 0.63, 0.47 and 0.52, while the cut-off values were 10.1 mgA/L, 10.3 mgA/L and 10.5 mgA/L, respectively. Sensitivity was ≤ 42% for all antigens, while specificity exceeded 89%. BLCA yielded cut-offs of 18.6, 14.9 and 13.7 mgA/L for f 1, f 2 and f 4, respectively, with similarly poor sensitivity and high specificity. IgG antibodies against rAsp f 1, f 2 and f 4 exhibit high specificity but poor sensitivity in identifying ABPA, limiting their utility as standalone diagnostic markers. ABSTRACT Background The diagnostic cut‐off values for IgG antibodies against recombinant Aspergillus fumigatus (rAsp) antigens in allergic bronchopulmonary aspergillosis (ABPA) remain unclear. Objectives To derive and validate diagnostic cut‐offs for IgG antibodies against rAsp f 1, f 2 and f 4 in ABPA and assess their diagnostic performance in distinguishing ABPA from asthma. Methods In this case‐control study, we prospectively enrolled consecutive subjects with asthma and ABPA. We measured serum IgG levels against rAsp f 1, rAsp f 2 and rAsp f 4 using a fluorescent enzyme immunoassay. Subjects were randomly split into derivation (50%) and validation (50%) cohorts. Cut‐offs were derived using receiver operating characteristic (ROC) curves and Youden's index. Additionally, we performed Bayesian latent class analysis (BLCA) using two‐component Gaussian mixture models to derive unbiased cut‐offs. Diagnostic performance was assessed using sensitivity, specificity and the area under the ROC curve (AUROC). Results Of 375 participants, 261 had ABPA and 114 had asthma. ROC‐derived AUROC values for rAsp f 1, f 2 and f 4‐IgG were 0.63, 0.47 and 0.52, while the cut‐off values were 10.1 mgA/L, 10.3 mgA/L and 10.5 mgA/L, respectively. Sensitivity was ≤ 42% for all antigens, while specificity exceeded 89%. BLCA yielded cut‐offs of 18.6, 14.9 and 13.7 mgA/L for f 1, f 2 and f 4, respectively, with similarly poor sensitivity and high specificity. Conclusions IgG antibodies against rAsp f 1, f 2 and f 4 exhibit high specificity but poor sensitivity in identifying ABPA, limiting their utility as standalone diagnostic markers. |
| Author | Dhooria, Sahajal Aggarwal, Ashutosh N. Chakrabarti, Arunaloke Prasad, Kuruswamy Thurai Garg, Mandeep Muthu, Valliappan Singh, Mani Agarwal, Ritesh Rudramurthy, Shivaprakash M. Sehgal, Inderpaul Singh |
| Author_xml | – sequence: 1 givenname: Ritesh orcidid: 0000-0003-2547-7668 surname: Agarwal fullname: Agarwal, Ritesh email: agarwal.ritesh@outlook.in organization: Postgraduate Institute of Medical Education and Research (PGIMER) – sequence: 2 givenname: Valliappan orcidid: 0000-0003-0410-8468 surname: Muthu fullname: Muthu, Valliappan organization: Postgraduate Institute of Medical Education and Research (PGIMER) – sequence: 3 givenname: Inderpaul Singh surname: Sehgal fullname: Sehgal, Inderpaul Singh organization: Postgraduate Institute of Medical Education and Research (PGIMER) – sequence: 4 givenname: Kuruswamy Thurai surname: Prasad fullname: Prasad, Kuruswamy Thurai organization: Postgraduate Institute of Medical Education and Research (PGIMER) – sequence: 5 givenname: Sahajal surname: Dhooria fullname: Dhooria, Sahajal organization: Postgraduate Institute of Medical Education and Research (PGIMER) – sequence: 6 givenname: Mani surname: Singh fullname: Singh, Mani organization: Postgraduate Institute of Medical Education and Research (PGIMER) – sequence: 7 givenname: Mandeep orcidid: 0000-0002-4714-6299 surname: Garg fullname: Garg, Mandeep organization: Postgraduate Institute of Medical Education and Research (PGIMER) – sequence: 8 givenname: Ashutosh N. surname: Aggarwal fullname: Aggarwal, Ashutosh N. organization: Postgraduate Institute of Medical Education and Research (PGIMER) – sequence: 9 givenname: Shivaprakash M. surname: Rudramurthy fullname: Rudramurthy, Shivaprakash M. organization: Postgraduate Institute of Medical Education and Research (PGIMER) – sequence: 10 givenname: Arunaloke orcidid: 0000-0003-1555-3807 surname: Chakrabarti fullname: Chakrabarti, Arunaloke organization: Doodhadhari Burfani Hospital |
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| Cites_doi | 10.1016/j.jaip.2025.03.005 10.1016/j.jaip.2023.04.009 10.1111/cea.13216 10.1016/j.alit.2020.07.006 10.1016/j.jaip.2020.08.043 10.1111/myc.13700 10.1111/all.13031 10.1136/bmj.329.7459.209 10.1016/j.ccm.2021.12.002 10.1186/1939-4551-6-17 10.1111/myc.13124 10.1016/j.jaip.2019.08.041 10.1111/cea.12590 10.1093/oxfordjournals.aje.a117428 10.1016/j.alit.2015.08.004 10.1183/13993003.00061-2024 10.1099/jmm.0.000991 10.1111/j.1553-2712.1996.tb03538.x |
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| Notes | This work was supported by ICMR, New Delhi [Grant no. 5/8/4‐3/COPD/2019‐NCD‐I]. PGIMER, Chandigarh [Grant no. 32762–318]. Funding ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 |
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Background
The diagnostic cut‐off values for IgG antibodies against recombinant Aspergillus fumigatus (rAsp) antigens in allergic bronchopulmonary... The diagnostic cut-off values for IgG antibodies against recombinant Aspergillus fumigatus (rAsp) antigens in allergic bronchopulmonary aspergillosis (ABPA)... Background The diagnostic cut‐off values for IgG antibodies against recombinant Aspergillus fumigatus (rAsp) antigens in allergic bronchopulmonary... |
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| SubjectTerms | Adult Allergic bronchopulmonary aspergillosis allergic bronchopulmonary mycosis allergy Antibodies Antibodies, Fungal - blood Antigens Antigens, Fungal - immunology Aspergillosis Aspergillosis, Allergic Bronchopulmonary - blood Aspergillosis, Allergic Bronchopulmonary - complications Aspergillosis, Allergic Bronchopulmonary - diagnostic imaging Aspergillosis, Allergic Bronchopulmonary - immunology aspergillus Aspergillus fumigatus Aspergillus fumigatus - immunology Asthma Asthma - blood Asthma - complications Asthma - diagnostic imaging Asthma - immunology Bayesian analysis Biomarkers - blood bronchiectasis Bronchiectasis - diagnostic imaging Bronchiectasis - etiology Case-Control Studies Diagnosis, Differential Enzyme immunoassay Female Humans Immunoglobulin G Immunoglobulin G - blood Male Mathematical models Middle Aged Prospective Studies Radiography, Thoracic Sensitivity and Specificity |
| Title | Cut‐Offs and Diagnostic Performance of IgG Against Recombinant Aspergillus fumigatus Antigens in Differentiating ABPA From Asthma |
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