Predominant Api m 10 sensitization as risk factor for treatment failure in honey bee venom immunotherapy.

BACKGROUND: Component resolution recently identified distinct sensitization profiles in honey bee venom (HBV) allergy, some of which were dominated by specific IgE to Api m 3 and/or Api m 10, which have been reported to be underrepresented in therapeutic HBV preparations. OBJECTIVE: We performed a retrospective analysis of component-resolved sensitization profiles in HBV-allergic patients and association with treatment outcome. METHODS: HBV-allergic patients who had undergone controlled honey bee sting challenge after at least 6 months of HBV immunotherapy (n = 115) were included and classified as responder (n = 79) or treatment failure (n = 36) on the basis of absence or presence of systemic allergic reactions upon sting challenge. IgE reactivity to a panel of HBV allergens was analyzed in sera obtained before immunotherapy and before sting challenge. RESULTS: No differences were observed between responders and nonresponders regarding levels of IgE sensitization to Api m 1, Api m 2, Api m 3, and Api m 5. In contrast, Api m 10 specific IgE was moderately but significantly increased in nonresponders. Predominant Api m 10 sensitization (>50% of specific IgE to HBV) was the best discriminator (specificity, 95%; sensitivity, 25%) with an odds ratio of 8.444 (2.127-33.53; P = .0013) for treatment failure. Some but not all therapeutic HBV preparations displayed a lack of Api m 10, whereas Api m 1 and Api m 3 immunoreactivity was comparable to that of crude HBV. In line with this, significant Api m 10 sIgG4 induction was observed only in those patients who were treated with HBV in which Api m 10 was detectable. CONCLUSIONS: Component-resolved sensitization profiles in HBV allergy suggest predominant IgE sensitization to Api m 10 as a risk factor for treatment failure in HBV immunotherapy.

Component resolution reveals additional major allergens in patients with honeybee venom allergy.

BACKGROUND: Detection of IgE to recombinant Hymenoptera venom allergens has been suggested to improve the diagnostic precision in Hymenoptera venom allergy. However, the frequency of sensitization to the only available recombinant honeybee venom (HBV) allergen, rApi m 1, in patients with HBV allergy is limited, suggesting that additional HBV allergens might be of relevance. OBJECTIVE: We performed an analysis of sensitization profiles of patients with HBV allergy to a panel of HBV allergens. METHODS: Diagnosis of HBV allergy (n = 144) was based on history, skin test results, and allergen-specific IgE levels to HBV. IgE reactivity to 6 HBV allergens devoid of cross-reactive carbohydrate determinants (CCD) was analyzed by ImmunoCAP. RESULTS: IgE reactivity to rApi m 1, rApi m 2, rApi m 3, nApi m 4, rApi m 5, and rApi m 10 was detected in 72.2%, 47.9%, 50.0%, 22.9%, 58.3%, and 61.8% of the patients with HBV allergy, respectively. Positive results to at least 1 HBV allergen were detected in 94.4%. IgE reactivity to Api m 3, Api m 10, or both was detected in 68.0% and represented the only HBV allergen-specific IgE in 5% of the patients. Limited inhibition of IgE binding by therapeutic HBV and limited induction of Api m 3- and Api m 10-specific IgG4 in patients obtaining immunotherapy supports recent reports on the underrepresentation of these allergens in therapeutic HBV preparations. CONCLUSION: Analysis of a panel of CCD-free HBV allergens improved diagnostic sensitivity compared with use of rApi m 1 alone, identified additional major allergens, and revealed sensitizations to allergens that have been reported to be absent or underrepresented in therapeutic HBV preparations.

Reduced adrenal stress response in patients on PCSK9 inhibitor therapy.

BACKGROUND AND AIMS: Treatment with proprotein convertase subtilisin-kexin type 9 inhibitors (PCSK9i), in addition to statin therapy, reduces LDL-cholesterol (LDL-c) in some patients to extremely low levels (i.e.< 20 mg/dl or < 0.52 mmol/l). There is concern that at such low levels, the physiologic role of cholesterol may be impaired, e.g. the adrenal cortisol stress response might be compromised. We therefore evaluated the effect of PCSK9i therapy on the cortisol response to ACTH in patients with LDL-c down to extremely low levels. METHODS: Nineteen patients on PCSK9i therapy and 18 controls matched for age, gender and comorbidities were included. The cortisol response to adrenocorticotropic hormone (ACTH) was tested after application of 250 µg ACTH. RESULTS: LDL-c levels ranged from 0.42 to 3.32 mmol/l (mean 1.38 ± 0.84 mmol/l) in the PCSK9i group and 0.81-4.82 mmol/l (mean 2.10 ± 0.97) in the control group. By analysis of covariance (ANCOVA), the PCSK9i group had significantly lower cortisol response compared to the control group (- 97.26 nmol/l, -178.60 to -15.93, p = 0.02) after 60 min. There was a significant positive correlation between the duration of PCSK9i treatment and cortisol levels (r = 0.59, p = 0.009). Extremely low LDL-c levels down to 0.42 mmol/l were not associated with lower stimulated cortisol levels. CONCLUSIONS: Patients on PCSK9i therapy showed a significantly lower cortisol response to ACTH. Stimulated cortisol levels were lower in the first months of PCSK9i treatment, suggesting an adaptive phenomenon. We conclude that the adrenal stress response in patients on PCSK9 inhibitor therapy is reduced.