Diagnosis of Allergic Bronchopulmonary Aspergillosis: A Case-Based Approach

Sahajal Dhooria; Ritesh Agarwal

Disclosures

Future Microbiol. 2014;9(10):1195-1208. 

In This Article

What Vision Do We Have for 2020 in the Field of ABPA Diagnostics?

New markers like recombinant Aspergillus antigens, thymus- and activation-regulated chemokine (TARC) and the FACS basophil CD203c assay are being evaluated for use in the diagnosis and followup of ABPA. They have the potential to become a routine tool in the armamentarium of 'ABPAologists' in 2020.

Recombinant A. fumigatus Antigens

Recombinant antigens are synthesized from cDNA libraries of A. fumigatus and can be produced as highly purified proteins. They may contribute to significant improvement in the diagnostic specificity and reproducibility as compared with crude extracts.[81] In ABPA, these antigens have been evaluated both for skin testing and measurement of specific IgE levels.[82–84] The most widely studied recombinant A. fumigatus antigens include rAsp f1 (secreted ribotoxin), rAsp f2 (unknown function), rAsp f3 (peroxisomal protein), rAsp f4 (unknown function) and rAsp f6 (cellular manganese superoxide dismutase).[85] Studies suggest that rAsp f4 and f6 represent specific markers for ABPA and allow a differentiation from Aspergillus-sensitized asthma.[85,86] The proposed reason for the specificity of rAsp f4 and f6 is that they are intracellular nonsecreted proteins.[87] Therefore, only patients suffering from ABPA get exposed to these proteins, as a result of fungal damage related to cellular defense mechanisms.[88] In contrast, A. fumigatus-sensitized asthmatics mount an IgE response only to secreted proteins (rAsp f1 and f3) produced shortly after spore germination.[89] One study suggested that serial determinations of IgE to rAsp f3 may provide improved distinction between stages of flares and remission compared with changes in IgE to a crude Aspergillus extract.[90] A combination of these antigens is more useful rather than using a single antigen.[91,92] Commercial automated assays for determination of specific IgE levels against recombinant A. fumigatus antigens are available.[92–94] Although detection of IgE response to recombinant Aspergillus antigens looks promising, there is literature that questions this claim.[86,95] Therefore, further scrutiny in larger controlled studies is obligatory before this test gets incorporated into the routine diagnostic workup in the clinic.[96]

Thymus- & Activation-regulated Chemokine/CCL17

ABPA is characterized by a Th2 type of immune response.[97] TARC acts as a chemoattractant to Th2 type of cells acting through CCR4 and CCR8 receptor present on these cells. TARC has been shown to have a better diagnostic accuracy as a sole marker than specific IgE to crude or recombinant A. fumigatus antigens with sensitivity of 100% and a specificity of 97.2% for ABPA diagnosis in CF.[98] It may also indicate exacerbations of ABPA better than IgE levels if serial determination is performed.[99] Large studies are required to evaluate the role of this novel marker in the diagnosis and followup of ABPA complicating asthma.

FACS Basophil CD203c Assay

Patients with CF complicated by ABPA display characteristic increases in blood basophil CD203c levels both at baseline and following in vitro stimulation with an allergenic extract of A. fumigatus compared with patients with CF alone and in CF colonized with A. fumigatus.[100] As with TARC, the role of this modality needs to be investigated in ABPA complicating asthma.

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