Background: An important advantage of allergen immunotherapy as compared to pharmacotherapy for allergic rhinitis is the long-term effect that persists after completing immunotherapy. The mechanism of the sustained effect of allergen immunotherapy is not completely understood. Methods: We conducted a 7-year study of monitoring allergen-specific basophil response and serological markers in 20 subjects with moderate-to-severe grass pollen-allergic rhinitis just before beginning and after up-dosing of subcutaneous grass pollen immunotherapy, before the first pollen season, and 1–2 years after completion of 3–5 years of treatment. Comparable untreated rhinitis subjects were followed at the same time points. Clinical outcomes included assessment of symptoms, use of rescue medication, and quality of life. The basophil response was also monitored after removal of IgG antibodies. Results: Basophil response assessed as area under the curve (AUC) halved during initiation of SCIT and was 55% lower 1–2 years after completing SCIT. In the untreated group, the basophil response remained comparable. Although immunotherapy-induced grass pollen-specific IgG4 levels decreased to near pre-immunotherapy levels after completing SCIT, the removal of IgG antibodies resulted in an increase in basophil response almost to the pre-immunotherapy levels. In untreated subjects, removal of IgG did not have any effect on basophil response. Conclusions: Grass pollen immunotherapy induces sustained suppression of the allergen-specific basophil response that persists after completion of treatment and could account for long-term clinical tolerance. It also seems to be associated with persistent blocking activity of IgG antibodies.
COBISS.SI-ID: 37928453
Background Adverse systemic reactions (SRs) are more common in honeybee venom immunotherapy (VIT) than in wasp VIT. Factors that might be associated with SRs during the honeybee VIT are poorly understood. Objective Our aim was to evaluate risk factors for SRs during the build-up phase of honeybee venom immunotherapy. Methods We included 93 patients who underwent ultra-rush honeybee VIT. The adverse SRs and their severity was compared to various immunological (sIgE, tIgE, basophil CD63 response, baseline tryptase, and skin tests), patient-specific (age, sex, cardiovascular conditions and medications, and other allergic diseases), and sting-specific factors (anaphylaxis severity, time interval to onset of symptoms, and absence of cutaneous symptoms). Results Twenty-three patients (24.7%) experienced mild SRs and 13 patients (14%) severe SRs. In five patients with severe SRs, the build-up was stopped. High basophil allergen sensitivity, evaluated as dose%response curve metrics of EC15, EC50, CD-sens, AUC, or the response to submaximal 0.01 %g/mL of venom concentration, was the most significant risk factor and only independent predictor of severe SRs and/or build-up stop. Time interval of (5 min after sting to onset of symptoms and lower specific IgEs to rApi m1 was also associated with severe SRs. There was no difference in other immunological, patient-specific, or sting-specific factors, including the baseline tryptase. None of the studied factors was associated with mild SRs. Conclusion and Clinical Relevance High basophil allergen CD63 sensitivity phenotype was a major indicator of severe adverse SRs during the build-up phase of honeybee VIT. Possibly role was also showed for short latency to filed sting reaction and low sIgE to rApi m1. Before honeybee VIT, measurement of basophil allergen sensitivity should be used to identify patients with a high risk for severe side-effects.
COBISS.SI-ID: 37963013
Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare autosomal dominant disease characterized by recurrent life-threatening oedemas and/or abdominal pain and caused by mutations affecting the C1 inhibitor gene, SERPING1. We sought to investigate the spectrum of SERPING1 mutations in Serbia and the possible genotype-phenotype association. C1-INH-HAE was diagnosed on the basis of clinical and laboratory criteria in 40 patients from 27 families; four were asymptomatic. Mutational analysis of the SERPING1 gene was performed by sequencing and multiplex ligation-dependent probe amplification. Disease-causing mutations in SERPING1 were identified in all patients. In C1-INH-HAE type I, we identified 19 different mutations, including 6 missense mutations, 6 nonsense mutations, 2 small deletions, 1 small insertion, 2 splicing defects and 2 large deletions. Two of the mutations (c.300C)T and c.1184_1185insTA) are reported here for the first time. All C1-INH-HAE type II patients from three families harboured the same substitution (c.1396C)T). Based on the type of mutation identified in the SERPING1 gene, patients were divided into two groups: group 1 (nonsense, frameshift, large deletions/insertions, splicing defect, and mutations at Arg444) or group 2 (missense, excluding mutations at Arg444). Significant differences were found in the clinical severity score (P = 0.005), prevalence of laryngeal (P = 0.040) and facial (P = 0.013) oedema, and long-term prophylaxis (P = 0.023) between the groups with different types of mutations. Because our population consisted of related subjects, differences in the severity score between mutation groups were further confirmed using the generalized estimating equation (P = 0.038). Our study identified 20 different disease-causing mutations, including two novel mutations, in all C1-INH-HAE patients, highlighting the heterogeneity of mutations in the SERPING1 gene. Furthermore, it appears that mutations with a clear effect on C1-INH function might be responsible for a more severe disease phenotype.
COBISS.SI-ID: 32308697
Background The influence of filaggrin gene (FLG) mutations on early- vs. late-onset development of atopic dermatitis (AD), allergic contact dermatitis (ACD) and chronic irritant contact dermatitis (CICD) is not completely understood. Objectives To assess the association between FLG mutations and development of AD, ACD and CICD. Methods This study assessed 241 patients with AD. AD developed during infancy in 85 patients, during childhood in 79 patients (32 early and 47 late) and during adulthood in 77 patients. We also included 100 patients with ACD and 44 with CICD, as well as 164 healthy controls. Four prevalent FLG loss-of-function mutations were genotyped (R501X, 2282del4, R2447X and S3247X). Results The 2282del4 mutation was significantly associated with a greater risk of AD in the entire group [odds ratio (OR) 4•33, 95% confidence interval (CI) 1•26–14•96]. However, the 2282del4 mutation was associated only with AD that developed during infancy or in early childhood (≤ 8 years: OR 20•91, 95% CI 2•73–159•9), not with AD development in late childhood or adulthood () 8 or ) 18 years), or ACD or CICD. Similar associations were also observed for the combined 2282del4 or R501X genotype. Carriers of FLG mutations also experienced a longer duration of AD and required hospitalization more often. Conclusions FLG mutations are associated with only the early onset of AD, not late onset. Other factors should receive attention in patients with late-onset AD.
COBISS.SI-ID: 37632261
Venom-specific immunotherapy (VIT) is considered for the treatment of patients with IgE-mediated systemic allergic reactions (SARs) after developing a Hymenoptera venom allergy. Tolerance is achieved in a majority of patients after only a few days or even hours of rush immunotherapy. After VIT discontinuation, the allergy returns in up to 15% of patients. During VIT, the majority of patients have local reactions at the site of venom injections. SARs to VIT are much more frequent in honeybee-treated patients than in wasp-treated patients. Increased baseline serum tryptase and increased allergen-specific sensitivity of basophils are other factors that might be associated with systemic reactions (SRs) during VIT. Severe SRs occur mainly during the build-up phase but can also occur in the maintenance phase of the VIT, even in patients with a well-tolerated dose-increase phase. Pre-treatment with humanized anti-IgE antibodies (omalizumab) is effective in patients with repeated SARs; however, this use of omalizumab is off-label. In highly exposed patients with a history of very severe reactions, there are virtually no absolute contraindications for VIT.
COBISS.SI-ID: 37947653