Effect of patient immunodeficiencies on the diagnostic performance of serological assays to detect Aspergillus-specific antibodies in chronic pulmonary aspergillosis

Abstract

Background Prevalence of chronic pulmonary aspergillosis (CPA) is ~3 million patients worldwide, and detection of Aspergillus -specific antibody is a critical diagnostic component. Some patients with CPA have subtle immune deficits possibly contributing to poor Aspergillus antibody production and false negative results. Materials/methods We analyzed patient data from 167 cases of clinically confirmed CPA previously evaluated by ImmunoCAP Aspergillus -specific IgG EIA, Bordier ELISA and LDBio Aspergillus IgG/IgM ICT lateral flow assay, to identify deficiencies in: mannose binding lectin (MBL), IgG, IgA, IgM, IFN gamma, IL12 or IL17 production, and/or low cell marker counts (CD4, CD19, CD56). We defined patients as ‘sero-negative’ if ImmunoCAP Aspergillus IgG was consistently and repeatedly negative (<40 mg A/L). ‘Sero-positive’ was defined as all other CPA cases. Results We found the rate of false negatives by ImmunoCAP Aspergillus IgG EIA (n = 23) to be more prevalent in patients with immunodeficiency markers, especially multiple defects. MBL deficiency combined with low CD19 cells (p < 0.001), pneumococcal antibody levels (p = 0.043), IgM (p = 0.047) or three combined (p = 0.001–0.018) or all four together (p = 0.018) were significant. The performance LDBio Aspergillus IgG/IgM ICT appears to be relatively unaffected by immunodeficiency (92.7% of ImmunoCap sero-negatives were positive). The Bordier assay performed significantly better than the ImmunoCAP assay ( P = 0.0016) for sero-negative CPA cases. Conclusions In select cases of CPA, ImmunoCAP EIA yields a false negative result, making serological diagnosis difficult. ImmunoCAP false negatives are more prevalent in patients with multiple immunological defects, who may still be positive with the LDBio Aspergillus ICT or Bordier EIA.

Chronic pulmonary aspergillosis is common among patients with presumed tuberculosis relapse in Ghana

“…We observed no significant statistical difference in the rate of CPA in HIV-positive patients and CPA in HIV-negative patients (6.8% vs 10.9%), contrary to other studies. 6 , 16 , 22 , 33 Though Aspergillus serology was positive in less than 10% of our screened patients, it contributed to greater than 90% of CPA diagnosis. One CPA patient who was HIV-positive had a negative Aspergillus IgG and IgM LFA result.…”

“…This maybe because of a reduced capacity to elicit production of antibodies; the correlation between immunodeficiency and negative Aspergillus serology has been previously described. 6 , 9 , 33 Unfortunately, the participant in the control group with a positive Aspergillus antibody test was unable to be reached for imaging and further laboratory investigations to evaluate the clinical relevance. It could have been a possible case of asymptomatic pulmonary aspergillosis or a false positive test.…”

Non- fumigatus Aspergillus Infection Associated with a Negative Aspergillus Precipitin Test in Patients with Chronic Pulmonary Aspergillosis

“…Disregarding Aspergillus species, it was suggested that host immunodeficiency may influence the positivity of Aspergillus antibody tests ( 11 ). In this study, to the best of our knowledge, there were no immunodeficiency factors associated with false-negative results in the Aspergillus precipitin tests.…”

“…In previous studies, the sensitivity of the precipitin test has ranged from 59% to 88% in patients with CPA ( 8 , 10 ). It was suggested that the false-negative results in Aspergillus antibody tests were caused by the host immune deficiency ( 11 ) and Aspergillus species ( 12 ). The causative organism associated most commonly with CPA is Aspergillus fumigatus , and the efficacy of Aspergillus antibody testing has been proven in most cases of A. fumigatus -associated CPA ( 8 , 13 ).…”

Importance of Aspergillus-Specific Antibody Screening for Diagnosis of Chronic Pulmonary Aspergillosis after Tuberculosis Treatment: A Prospective Follow-Up Study in Ghana

“…The performances of some Aspergillus -specific antibody assays are negatively affected by the relatively common minor or subtle immunodeficiencies found in CPA patients. However, the LDBio Aspergillus -specific IgG and IgM assay has been previously reported to be minimally affected by immunodeficiency, and thus, it may perform acceptably well in both HIV seronegative and seropositive patients [ 29 ]. Notwithstanding, CPA is rarely associated with HIV, and it is more common in patients without apparent or with subtle immunodeficiency.…”