The diagnosis of CF-ABPA is a more difficult task than diagnosing ABPA without cystic fibrosis . The diagnostic criteria developed to differentiate this disease is also different from those followed in the diagnosis of non-CF-ABPA. Elevated serum total IgE, a common feature considered significant in the diagnosis of ABPA without cystic fibrosis is not as reliable in the differential diagnosis of ABPA with cystic fibrosis [1, 12]. Skin test reactivity and the presence of specific IgG are also considered important in the diagnosis of ABPA with and without CF. The multi-functional discriminant analysis using IgE, IgG, IgA and the different recombinant allergens yielded significant results in the differentiation of different patient groups.
It has been shown that crude extract from A. fumigatus is a useful reagent for demonstrating specific IgG and IgE from most ABPA patients [14–17]. However, a number of CF patients with and without asthma also demonstrated high levels of both antibodies. Purified recombinant allergens have shown more specificity compared to other allergen preparations when ABPA patients without CF were studied [6, 18]. Asp f 1 showed non-specific reactivity with normal controls and CF patients with and without ABPA. However, ABPA patients without cystic fibrosis consistently demonstrate specific antibodies to Asp f 2 compared to other purified recombinant Af allergens [6, 9]. In combination with Asp f 3, f 4, and f 6 a number of patients with ABPA demonstrated specific IgE in significant levels. These purified antigens also showed more sensitivity and specificity in comparing patients with ABPA to simple Af allergy.
From the results presented, it can be seen that Asp f 2 demonstrated specific IgE in the sera of CF-ABPA patients, but also showed reactivity with asthmatics and CF patients without any allergy, i.e. high sensitivity, but low specificity. On the other hand, Asp f 3 showed high specificity, but with low sensitivity. Although previous studies have shown that Asp f 3 was significant in differentiating the CF patient groups due to the presence of high levels of Aspergillus specific IgE in their sera, we did not find this clear cut difference in the present study [9, 16].
In evaluating the ELISA and ImmunoCAP methods, our results indicate that the former was more specific, but less sensitive. The ImmunoCAP of recombinant allergens reacted with more patients and demonstrated Af specific IgE in the sera of ABPA with CF. Similarly a number of asthmatics and CF without allergy also showed high levels of specific IgE to the various antigens included in the ImmunoCaps. ImmunoCAP of crude Aspergillus extract demonstrated IgE in over 95% of ABPA-CF, but also reacted with over 78% of asthmatics and 40% of CF patients. Thus, the comparative specificity of ImmunoCap using either crude or purified recombinant allergens of Aspergillus is inferior to ELISA, but the latter is also not sufficiently predictive to be acceptable as a reliable diagnostic assay.
The usefulness of specific IgG subclasses in the diagnosis of CF-ABPA has been previously suggested . Although, similar elevations in the levels of IgG1 and G4 were noted in both CF groups in the present study, these differences were not statistically significant. The discriminant function analysis using all features simultaneously classified most patients in their respective groups. Although all the 17 ABPA-CF patients showed difference in their antibody response, the results on comparison with other groups of patients was found to be significant (Table 1). Generally a discriminant capability of at least 90% is indicated for adapting a test for differential diagnosis (Figure 3).