There is no detailed comparison of allergen-specific immunoglobulin responses following sublingual (SLIT) and subcutaneous (SCIT) immunotherapy.

To compare nasal and systemic Timothy grass pollen (TGP)-specific antibody responses during two years of SCIT and SLIT and one year after treatment discontinuation in a double-blind, double-dummy, placebo-controlled trial.

Nasal fluid and serum were obtained yearly (per-protocol population, n=84). TGP-specific IgA1, IgA2, IgG4, IgG and IgE were measured in nasal fluids by ELISA. TGP-specific IgA1, IgA2 and Phl p1, 2, 4, 5b, 6, 7, 11 and 12 IgE and IgG4 were measured in sera by ELISA and ImmunoCAP, respectively.

At years 2 and 3, TGP-IgA1/2 in nasal fluid were elevated in SLIT compared to SCIT (4.2 and 3.0-fold for IgA1, 2.0 and 1.8-fold for IgA2, respectively; all P<.01). TGP-IgA1 in serum was elevated in SLIT compared to SCIT at years 1, 2, and 3 (4.6, 5.1, and 4.7-fold, respectively; all P<.001). Serum TGP-IgG was higher in SCIT compared to SLIT (2.8-fold) at year 2. Serum TGP-IgG4 was higher in SCIT compared to SLIT at years 1, 2, and 3 (10.4, 27.4, and 5.1-fold, respectively; all P<.01). Serum IgG4 to Phl p1, 2, 5b and 6 were increased at years 1, 2 and 3 in SCIT and SLIT compared to placebo (Phl p1: 11.8 and 3.9-fold; Phl p2: 31.6 and 4.4-fold; Phl p5b: 135.5 and 5.3-fold; Phl p6: 145.4 and 14.7-fold, respectively, all at year 2 when levels peaked; P<.05). IgE to TGP in nasal fluid increased in the SLIT group at year 2 but not year 3 compared to SCIT (2.8-fold; P=.04) and placebo (3.1-fold; P=.02). IgA to TGP and IgE and IgG4 to TGP-components stratified participants according to treatment group and clinical response.

The observed induction of IgA1/2 in SLIT and IgG4 in SCIT suggest key differences in the mechanisms of action.

Allergy to house dust mites (HDM), the most important source of indoor allergens worldwide, is diagnosed and treated using natural extracts from cultures that can contain immunoactive components from the HDM microbiome, including mite-infecting viruses.

Discovery and characterization of RNA viruses from Dermatophagoides pteronyssinus, followed by detection in different mite-derived sources.

Viruses were assembled after in silicometatranscriptomic analysis of D.pteronyssinus RNA samples, visualized by electron microscopy, and RNA detected by direct RT-PCR or data mining. Mite culture performance was evaluated in vivo.

Seven RNA viruses were identified in our laboratory stock colony. Picornavirus-like viral particles were detected in epithelial cells of the digestive system and in fecal pellets. Most of these viruses could be persistently transmitted to an inbred virus-free colony by inoculating fecal material from the stock colony. Upon viral infection, no significant effect could be seen on mite population growth. Transcriptomic screening confirmed the presence of homolog sequences to these viruses in independent laboratory stocks of D. pteronyssinus and in other Astigmata mites. Noteworthy, RNA from most of the viruses could be detected by RT-PCR on house dust samples, reference standards, and/or commercial diagnostic D. pteronyssinus extracts.

Our results show that viral infections are common and widespread in D. pteronyssinus, both in natural and culture-based growth conditions. Potential effects on the mites themselves and consequences towards allergenicity in humans whether exposed naturally or after immunotherapy are discussed.

The standardised quality (SQ) tree sublingual immunotherapy (SLIT)-tablet has recently been approved for treatment of tree pollen allergy. Health care workers should be provided with detailed safety data for clinical use.

To assess the tolerability and safety of the SQ tree SLIT-tablet (12 SQ-Bet)in adults and adolescents.

Safety data were pooled fromthree double-blinded, randomized, placebo-controlled trials (2 phase-II/1 phase-III) including adults and adolescents 12-65 years with allergic rhinitis and/orconjunctivitis treated before and during one pollen season once-daily with 12 SQ-Bet (n=471) or placebo (n=458): EudraCTno:2012-000031-59; NCT02481856; EudraCT 2015-004821-15.

The most frequently reported investigational medicinal product(IMP)-related AEs with 12 SQ-Bet were oral pruritis (39% of subjects)and throat irritation (29%).IMP-related AEs were mainly mild or moderate in severity,and the majority resolved without treatment and did not lead to treatment interruption/discontinuation. With 12 SQ-Bet, oral pruritus was more frequent among subjects with pollen food syndrome (PFS) (45%) than without PFS (29%).The 12 SQ-Bet did not seem to induce an increased risk of asthma: 7 events were reported in 7 subjects with 12 SQ-Bet and 11 in 10 subjects with placebo. No differences were seen in the risk of moderate to severe IMP-related AEs regardless of age, PFS status and asthma medical history.

The 12 SQ tree SLIT-tablet was well tolerated in tree pollen allergic subjects with no major safety concerns detected.This safety profile supports daily at-home sublingual administration once the first dose is tolerated when administered under medical supervision.

Background: Mastocytosis is a risk factor for hymenoptera venom anaphylaxis (HVA). Current guidelines recommend measuring tryptase in HVA patients and that those with mastocytosis pursue lifelong venom immunotherapy (VIT). Available data on HVA and mastocytosis largely derives from European single-center studies and the prevalence of HVA with and without mastocytosis in the United States (US) is unknown.

We sought to determine the prevalence of HVA and mastocytosis in the US using an insurance claims database and evaluate the impact oo determine the prevalence of HVA and mastocytosis in the US using an insurance claims database and evaluate the impact of mastocytosis on VIT in HVA patients in a US cohort.

The IBM Watson Database, consisting of insurance claims from approximately 27 million US patients in 2018, was queried to identify patients with HVA and/or mastocytosis. Further, a retrospective study of 161 patients undergoing VIT between 2015 - 2018 at the University of Michigan (U-M) was conducted.

In the IBM Watson Database, the prevalence of HVA was 167 per 100,000 (0.167%) and the prevalence of mastocytosis 10 per 100,000 (0.010%) overall and 97 per 100,000 (0.097%) among those with HVA. Mastocytosis showed a 9.7-fold increase among HVA patients versus the general population. In the U-M cohort, 2.6% of VIT patients had mastocytosis. Tryptase level did not correlate with venom reaction severity but was higher in patients with systemic VIT reactions.

We observed a lower US HVA prevalence than previously reported. Mastocytosis was more common in US HVA patients, though at lower rates than previously reported. In VIT patients there was no correlation between tryptase level and reaction severity.

The objective of this study was to determine the role of thrombin-activatable fibrinolysis inhibitor (TAFI) as a candidate biomarker for therapeutic efficacy of sublingual immunotherapy (SLIT) and to identify the role of TAFI in the pathogenesis of allergic rhinitis (AR).

Retrospective cohort study and laboratory study.

Serum was collected from patients with allergies to Japanese cedar pollen before, during, and after treatment with SLIT. We measured the levels of immunoreactive TAFI, C3a, and C5a in serum by enzyme-linked immunosorbent assay (ELISA) and assessed their relative impact on a combined symptom-medication score. We also examined the impact of TAFI on mast cells and fibroblasts in experiments performed in vitro.

Serum levels of TAFI increased significantly in response to SLIT. By contrast, serum C3a levels decreased significantly over time; we observed a significant negative correlation between serum levels of TAFI versus C3a and symptom-medication score. Mast cell degranulation was inhibited in response to TAFI, as it was the expression of both CCL11 and CCL5 in cultured fibroblasts.

High serum levels of TAFI may be induced by SLIT. TAFI may play a critical protective role in pathogenesis of AR by inactivating C3a and by inhibiting mast cell degranulation and chemokines expression in fibroblasts.

There are no indices to monitor desensitization by low-dose egg oral immunotherapy (eOIT).

We aimed to examine the relationship between desensitization by low-dose eOIT and the changes in allergen-specific immunoglobulin E (IgE) and IgG4 levels.

We carried out low-dose eOIT in 31 patients with severe egg allergy in our previous two studies. After 4 months of treatment, the patients with no observed allergic symptoms in response to the open hard-boiled egg white challenge tests were classified as the negative group, and the remaining patients, the positive group. The fold-difference levels were calculated using 10 Log (Titer after eOIT/Titer before eOIT).

Results: The 28 patients who completed eOIT with sufficient serum collected before and after eOIT were analyzed. The median fold-difference levels of ovomucoid-specific IgE in the negative and positive groups were 0.819 and 0.953, respectively (P = 0.082). The median fold-difference levels of ovalbumin-specific IgG4 in the negative and positive groups were 2.01 and 1.29, respectively (P = 0.057). In the receiver-operating characteristic curves, the area under the curves of fold-difference ovomucoid-specific IgE and ovalbumin-specific IgG4 were 0.701 and 0.719, respectively. The challenge positive predictive values of fold-difference ovomucoid-specific IgE and ovalbumin-specific IgG4 were 83.8% (cut-off point: 0.934) and 77.8% (cut-off point: 1.87), respectively. Moreover, the challenge positive predictive value in patients with both 0.934 < ovomucoid-specific IgE and ovalbumin-specific IgG4 <1.87 was 100%.

The fold-difference levels of allergen-specific IgE and IgG4 in serum are considered useful for monitoring desensitization by low-dose OIT.

Additional information is needed to inform optimal patient selection, expected outcomes, and treatment endpoints for clinical peanut oral immunotherapy (OIT).

We analyzed a real-world peanut OIT cohort to provide insight into these questions.

Records were reviewed for 174 children undergoing peanut OIT at a pediatric allergy clinic. Patient age, peanut skin prick test, peanut-specific IgE (sIgE) results, and inclusion of additional foods in OIT were analyzed for correlations with OIT outcomes.

To date, 144 patients have achieved maintenance dosing, 50 of whom transitioned to ad lib twice-weekly peanut ingestion. Thirty discontinued OIT. Fortyseven patients who underwent multi-food OIT had no significant difference in reactions or time to reach maintenance compared to those on peanut OIT alone. Age at initiation inversely correlated with achievement of maintenance: 92% of patients 0.5-<5 years, 81% of those 5-<11 years, and 70% of those 11-<18 years reached and continued maintenance (P=0.013). Baseline peanut-sIgE level positively correlated with number of reactions during updosing (P=0.0004) and maintenance (P=0.0048), though was not significantly different in patients achieving successful maintenance versus those who discontinued OIT (P=0.098). Sixty-six percent of patients experienced ≥1 adverse reaction during OIT. Of those on ad lib peanut ingestion, 2 reported mild reactions after lapses in peanut consumption.

Clinical peanut OIT has similar outcomes to research protocols. OIT can be successful in older children and those with high peanut-sIgE levels, though these factors impact outcomes. Clinical and laboratory criteria can guide successful transition to intermittent ad lib peanut consumption.

To determine whether subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT) better improves patient outcomes and quality of life for adults with allergic rhinitis or rhinoconjunctivitis (AR/C) with or without mild to moderate asthma.

Systematic review methodology was based on the Cochrane Collaboration handbook and Preferred Reporting Items for Systematic Reviews and Meta-analyses. Four databases (PubMed, Cochrane Library, EMBASE, and Web of Science) were queried from inception to July 30, 2020. Two independent reviewers screened potentially relevant studies and assessed risk of bias. Outcomes of interest were symptom score (SS), medication score (MS), combined symptom medication score (CSMS), and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). Meta-analyses with an adjusted indirect comparison were conducted in RevMan 5.4.1.

Seven SCIT versus SLIT randomized controlled trials (RCTs) demonstrated no significant differences for any outcomes, but insufficient data precluded direct meta-analysis. For the adjusted indirect comparison, 46 RCTs over 39 studies were included for SCIT versus placebo (n = 13) and SLIT versus placebo (n = 33). Statistically significant results favoring SCIT were found for SS (standardized mean difference [SMD] = 0.40; 95% confidence interval [CI] = 0.31-0.49), MS (SMD = 0.26; 95% CI = 0.14-0.39), CSMS (SMD = 0.42; 95% CI = 0.17-0.67), and RQLQ (MD = 0.24; 95% CI = 0.04-0.44). Statistically significant results favoring SLIT were found for SS (SMD = 0.42; 95% CI = 0.32-0.53), MS (SMD = 0.40; 95% CI = 0.28-0.53), CSMS (SMD = 0.37; 95% CI = 0.29-0.45), and RQLQ (MD = 0.32; 95% CI = 0.20-0.43). No significant differences were found between SCIT and SLIT for SS (SMD = -0.02; 95% CI = -0.15 to 0.11), MS (SMD = -0.14; 95% CI = -0.31 to 0.03), CSMS (SMD = 0.05; 95% CI = -0.21 to 0.31), or RQLQ (MD = -0.08; 95% CI = -0.31 to 0.15).

SCIT and SLIT are comparably effective treatments for adults with AR/C. More RCTs analyzing SCIT versus SLIT are needed to directly compare the two

The purpose of this study was to determine whether the sensitivity advantage of intradermal dilutional testing (IDT) is clinically relevant in patients with obstructive Eustachian tube dysfunction (ETD) or otitis media with effusion (OME). This retrospective, private-practice cohort study compared the sensitivity of skin prick tests (SPT) vs. IDT in 110 adults and children with suspected allergy and OME. Primary outcome measure was symptom resolution from allergy immunotherapy (AIT). IDT identified 57% more patients as being allergic, and 8.6 times more reactive allergens than would have been diagnosed using only SPT. Patients diagnosed by IDT had the same degree of symptom improvement from immunotherapy, independent of allergen sensitivity (66% by SPT vs. 63% by IDT; p = 0.69, not different). Low-sensitivity allergy tests, which may fail to identify allergy in over two thirds of children aged 3 to 15 as being atopic, or among 60% of patients with ETD, may explain why many physicians do not consider allergy as a treatable etiology for their patient's OME/ETD. IDT offers superior sensitivity over SPT for detecting allergens clinically relevant to treating OME/ETD. These data strongly support increased utilization of intradermal testing and invite additional clinical outcome studies.

Subcutaneous allergen immunotherapy (SCIT) is an effective treatment for allergic rhinitis, asthma, and venom allergy. Compliance is essential for SCIT to obtain maximal benefit as it is a long-term treatment.

This study aimed to determine the level of real-life SCIT compliance in pediatric patients and the associated factors. Additional aims were to determine how SCIT compliance was affected by the COVID-19 pandemic and why some patients dropped out SCIT.

Pediatric patients diagnosed with allergic rhinitis, allergic asthma, or venom allergy that received SCIT between September 2012 and July 2020 were analyzed.

The study included 201 children (66.7% male) with a median (interquartile range) age of 12.8 years (9.4-15.2) at the time of the first SCIT injection. The overall compliance rate before COVID-19 pandemic was 86.1%. Short SCIT follow-up time and venom anaphylaxis were found to be risk factors for drop out. The leading causes of drop outs were moving to another city/country (32.1%), symptom improvement (17.8%), treatment ineffectiveness (14.2%), and adverse reactions (14.2%). Among the 108 patients that were still receiving SCIT during the COVID-19 pandemic, 31 (28.7%) dropped out the therapy. The most frequent reasons for drop-out were fear of being infected with COVID-19 (35.4%) and thinking that the AIT practise stopped due to COVID-19 pandemic (29%). Male gender and older age were found to be the independent risk factors for drop-out of SCIT.

Real life compliance in children was found 13.9% and it was higher than adults. Nearly one-third of children dropped out during the CO-VID-19 pandemic. Male gender and older age are associated with SCIT drop-out during the COVID-19 pandemic.