The diagnosis and management of allergy is complex; the clinical symptoms associated with allergic reactions span a broad spectrum of severity, from mild hay fever-type symptoms through to life-threatening anaphylaxis. Obtaining an allergy-focused clinical history is therefore vital for identifying possible allergic triggers and directing testing. However, this focus could be changing as scientific and technological advances have paved the way for developments within in vitro testing for allergy. With knowledge of allergens at the molecular level expanding, there are now the facilities to characterize the sensitization profiles of allergy sufferers and determine the specific molecules (or components) against which the allergen-inducing immunoglobulin type E proteins have been produced. This technology is termed component-resolved diagnostics. We know that accurate identification of immunoglobulin type E specificity, the source of the causative allergen, and knowledge of potential allergic cross-reactivities are required for optimal clinical management of allergy patients. These factors can make allergy a diagnostic challenge outside of a specialist centre, and contribute to the difficulties associated with requesting and interpreting allergy tests. The incorporation of component-resolved diagnostics into current practice has provided a platform for patient-tailored risk stratification and improved the application of allergen-specific immunotherapy, revolutionizing specialist management of these patients. This review discusses the roles of each type of testing in allergy management and predictions for future pathways.
SummaryThe clinical utility of molecular diagnostic approaches in allergy investigation is increasingly being recognized to play a significant role in the management of allergic patients. Determining the sensitisation pattern, which is best achieved through the use of component resolved diagnostics (CRD), allows effective risk stratification, appropriate treatment and patient selection for immunotherapy.In order to assess the diagnostic service provisions for in vitro allergy testing across Europe, a survey was carried out via the total IgE and Specific IgE external quality assurance schemes run by UK NEQAS Immunology, Immunochemistry & Allergy.This survey assessed allergy testing and in particular allergen-components offered by the laboratories and found a wide variability in service provision, particularly between the UK and EU. Furthermore, there was lack of standardisation for acquisition of clinical information to aid allergen (and component) selection, gating strategy, testing algorithms and clinical interpretation. Interestingly, a significant proportion of laboratories (the majority from EU) stated that they 'used' the results for peanut components for risk stratification. However, vast majority of participants were unaware of guidelines relating to the use of allergen component testing and agreed further education would assist in reaching a common platform.
Background/Aims The idiopathic inflammatory myopathies (IIMs) are associated with a number of antibodies which are linked to certain clinical phenotypes. The presence of anti-transcriptional intermediary factor-1 gamma (TIF-1y) is strongly associated with malignancy. However, it is uncertain whether the presence of this antibody, in the absence of IIM, should prompt further investigations to exclude an underlying malignancy. Methods Patients were identified who had undergone myositis immunoblot testing at Liverpool University Foundation Trust laboratories as part of their clinical care between January 2015 and January 2020. Adult patients were included if they tested TIF-1y antibody positive but had no evidence of IIM. Data was collected on patient demographics, whether this was a weak or strong antibody finding and whether there was the presence of other antibodies on the immunoblot panel. The clinical notes were then used to assess whether the patient was known to have a malignancy or went on to develop a malignancy during the follow up period. Results The presence of TIF-1y antibody occurred in 66 patients. Four patients were excluded from analysis, three due to a diagnosis of IIM and one due to a lack of clinical information. The average age was 69 years (range 35 - 88 years) and 59% were female. A strongly positive TIF-1y antibody was found in 19 patients, of which eight were associated with another positive antibody available on the immunoblot panel. There were five malignancies identified, two were historic diagnoses, one patient was found to have a lung malignancy at the time the panel was sent and two patients subsequently developed pancreatic malignancy. A weakly positive TIF-1y antibody was found in 43 patients, of which 16 results were associated with another positive antibody on immunoblot analysis, excluding three patients with a positive anti-Ro antibody. Of 11 patients with malignancy, five had a historic diagnosis and six patients developed malignancy over the follow up period. Conclusion The myositis immunoblot is a useful tool in patients with IIM. However, when used outside of this context can produce a number of positive results, the significance of which are unclear. In the case of TIF-1y and its known association with malignancy, this can lead to unnecessary investigations and increase patient anxiety. This data has obvious limitations as there may have been incomplete information if patients were managed elsewhere and the presence of TIF-1y did not lead to investigation for underlying malignancy in the majority of patients, meaning some cancers may have been present but remained undetected. The results do not suggest the presence of this antibody increases the likelihood of malignancy in patients without IIM but further studies are recommended. Disclosure C.V. Cotton: None. C. Keymer: None. Z. McLaren: None.
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