Tackling penicillin allergy delabeling with ultra-sensitive in vitro
test and human-like specific IgE standards
Abstract
Background: Penicillin allergy delabeling initiatives are now
part of antibiotic stewardship programs and include the use of invasive
and risky in vivo tests. Instead, the quantification of specific
IgE is highly useful to confirm immediate allergy to penicillins.
However, discrepant results associated to the low sensitivity of the
in vitro tests have limited their routine diagnostic use for
delabeling purposes. We aimed to tackle a novel diagnostic strategy for
specific IgE testing based on a homologous interpolation scheme, using
recombinantly produced standards. Methods: Serum samples from a
cohort of allergic patients and controls were analysed by a
chemiluminescence-based immunoassay, using a bispecific binanobody as
standard. The novel standard targets the major antigenic determinant of
penicillin G and the paratope of Omalizumab, acting as human-like
specific IgE. Results: Testing a cohort of 65 human serum
samples, the method achieved a good agreement and strong positive
relationship, reaching a limit of detection below 0.1 IU/mL. The
sensitivity of the in vitro test significantly increased (66 %),
doubling that of the ImmunoCAP reference in vitro assay with an
overall specificity of 100 %. Conclusions: The new diagnostic
strategy compares favourably with the results obtained on the ImmunoCAP
system, paving the way towards the standardization of penicillin allergy
testing. The recombinant standards are potent calibrators, highly
stable, easy and inexpensive to produce, and overcome the limitation
associated with preparations derived from pooled human serum, expediting
the production of next generation standards with different specificities
to successfully tackle β-lactam allergy delabeling by in vitro
tests.