Diagnostic cut-offs and clinical utility of recombinant Aspergillus fumigatus antigens in the diagnosis of allergic bronchopulmonary aspergillosis.

Author: 

Muthu V, Singh P, Choudhary H, Sehgal IS, Dhooria S, Prasad KT, Aggarwal AN, Garg M, Chakrabarti A, Agarwal R.
J Allergy Clin Immunol Pract. 2019 Sep 11. pii: S2213-2198(19)30766-4.

Abstract: 

BACKGROUND:

The clinical utility of IgE against recombinant Aspergillus fumigatus-specific (rAsp) antigens in allergic bronchopulmonary aspergillosis (ABPA) remains unclear.

OBJECTIVE:

To identify the optimal diagnostic cut-offs of rAsp-specific IgE in differentiating ABPA from A.fumigatus-sensitized asthma (ASA), and define their utility in the diagnosis of ABPA.

METHODS:

We enrolled consecutive subjects of ASA and ABPA. IgE against rAsp f1, f2, f3, f4, and f6 was assayed in all the subjects. We evaluated three fixed cut-offs (0.35, 0.5, and 1.0 kUA/L) for their diagnostic performance in the entire cohort. We also divided the study population into derivation and validation cohorts. Cut-offs for rAsp-specific IgE were obtained using the receiver operating characteristic (ROC) analysis in the derivation cohort. We then evaluated the diagnostic performance of these cut-offs in the validation cohort. We further correlated rAsp-specific IgE levels in ABPA with asthma control, spirometry, imaging, and immunological markers.

RESULTS:

We included 194 subjects (123 ABPA and 71 ASA). The statistically derived cut-offs proved superior to fixed cut-offs. IgE against rAsp f1 yielded the best combination of sensitivity (89%) and specificity (100%). The sensitivity and specificity of IgE against either rAsp f1 (cut-off, 4.465 kUA/L) or f2 (cut-off, 1.300 kUA/L) for diagnosing ABPA was 100% and 81%, respectively. The correlation between rAsp-specific IgE and most clinical parameters of ABPA was weak.

CONCLUSION:

IgE against rAsp f1 and f2 (using ROC derived cut-offs) were found to be the most useful in differentiating ABPA from ASA. Due to conduct at single-center, our results require further validation.

KEYWORDS:

ABPM; allergic fungal airway disease; allergy; asthma; component-resolved diagnostics; fungal sensitization; molecular allergology; molecular diagnostics.