This Week in Allergy & Immunology — Jun 13, 2026

Welcome to This Week in Allergy & Immunology. This week we're covering disparities in care for hereditary angioedema, the complexities of discontinuing biologics in severe asthma, and novel immunomodulatory strategies from basic science to new vaccine platforms. Let's dive in.

We begin with the challenge of stratifying care in chronic allergic and inflammatory diseases. A key question for clinicians is when, and in whom, we can safely stop biologics for severe asthma. A retrospective cohort study in Allergology International provides some real-world answers [7]. Researchers analyzed 118 adults who discontinued biologics after at least one year of treatment. The good news is that at 12 months post-discontinuation, the estimated exacerbation-free probability was 65%. Factors associated with successful discontinuation were a robust clinical response and no exacerbations before stopping. Conversely, factors predicting post-discontinuation exacerbations included baseline blood eosinophilia of 300 cells per microliter or more, residual sputum symptoms even while on biologics, and discontinuing due to inadequate response or financial reasons. The risk also appeared to be class-dependent: persistent sputum was a significant risk factor after stopping anti-IL-5 therapies, while baseline eosinophilia was a risk factor after stopping anti-IgE or anti-IL-4-receptor-alpha agents. This highlights the need for careful patient selection and phenotype-specific considerations when planning de-escalation. From refractory asthma, we turn to refractory allergic rhinitis. A paper in The Journal of Allergy and Clinical Immunology explores the molecular drivers of steroid resistance [3]. The study focused on epithelial remodeling, specifically squamous metaplasia, a common finding in these patients. Transcriptomic analysis identified a protein called SPRR2A as a key marker associated with this metaplasia. The researchers found that IL-17A induces a keratin remodeling program driven by SPRR2A, which in turn upregulates another protein, CSTA. This SPRR2A-CSTA axis promotes squamous differentiation and induces glucocorticoid receptor beta, a known mediator of steroid resistance. In mouse models, deleting Sprr2a prevented squamous metaplasia and restored steroid responsiveness. Clinically, elevated serum levels of SPRR2A and CSTA were able to distinguish steroid-resistant from steroid-responsive AR patients, suggesting this axis could be a future therapeutic target and a valuable biomarker pathway. Beyond biological stratification, a study in The Journal of Allergy and Clinical Immunology: In Practice underscores the critical role of social determinants of health [2]. Using a large United States insurance claims database, researchers examined healthcare utilization among newly diagnosed hereditary angioedema patients. The findings revealed significant disparities. Patients from lower-income households—making less than $50,000 annually—had a roughly 44% higher risk of emergency department visits compared to those from higher-income households. Race and ethnicity were also major factors. Black patients had a 50% higher risk of an HAE-related ED visit, more than double the rate of ED visits, and more than double the rate of hospitalizations compared to White patients. Hispanic and Latino patients also had higher rates of ED visits. Critically, access to an allergist or immunologist was lower among Black patients and those from lower-income households compared to the overall study population. These data highlight that social and economic factors are powerful drivers of outcomes in HAE, demanding targeted strategies to ensure equitable access and care.

This week also saw two exciting papers that move beyond suppressing inflammation and toward actively re-shaping the immune response, one uncovering a new regulatory cell and the other designing a novel therapeutic. First, a landmark paper in Nature identifies a previously unknown subset of regulatory T cells controlling intestinal inflammation [6]. The researchers describe GPR15-guided regulatory CD8+ T cells, which use the G-protein coupled receptor GPR15 to home to the gut. Once there, these cells potently kill inflammatory macrophages, acting as a crucial brake on inflammation. The clinical relevance is direct and compelling: the study found that deleterious gene variants in GPR15 in humans are associated with severe, early-onset inflammatory bowel disease and defective homing of these regulatory cells. This discovery not only provides new insights into organ-specific immune regulation but also points to GPR15 as a potential therapeutic target for IBD. Building on the theme of inducing regulation, a preclinical study in The Journal of Allergy and Clinical Immunology presents a novel therapeutic strategy for allergies [5]. Investigators used an allergen-encoded messenger RNA-lipid nanoparticle vaccine, similar to the technology in COVID-19 vaccines. When given alone, this vaccine elicited a mix of T helper 1 and cytotoxic CD8 T-cell responses that counterbalanced the allergic Th2 response. However, when they co-administered the vaccine with an mTOR inhibitor, the immune profile shifted dramatically. This combination promoted the generation of functional regulatory T cells while toning down the cytotoxic response. This combinatorial strategy maintained the anti-allergic effects but limited vaccine-associated cytotoxicity in their mouse model of allergic asthma. This presents a potential strategy to enhance regulatory immunity and promote tolerance in the treatment of allergic diseases.

We'll finish with two papers that zoom in on antigen-specific responses, one defining reaction thresholds in food allergy and the other dissecting immune memory after vaccination and infection. First, the Nut CRACKER study in Allergy provides crucial data on cashew allergy, a common and often severe food allergy [1]. In a large cohort of 293 patients undergoing oral food challenges, researchers determined the eliciting doses for reactions. The ED05, or the dose causing a reaction in 5% of the allergic population, was about 1.2 mg of cashew protein cumulatively. More strikingly, the validated safe dose for 90% of the population was just 0.1 mg of protein, far lower than the 7.5 to 10 mg seen for peanut or walnut. This underscores the high potency of cashew as an allergen. The study also identified predictors of lower reaction thresholds, including co-allergy to pistachio and higher specific IgE levels to cashew, its component Ana o 3, and pistachio. These findings have direct implications for patient counseling and precautionary allergen labeling. Finally, a study in Science Translational Medicine examines how our immune system adapts to evolving viruses, using SARS-CoV-2 as a model [4]. Researchers analyzed memory B cell responses in individuals who had been previously vaccinated and then received either a Wuhan-1, variant, or bivalent booster. They found that variant boosters and subsequent Omicron infections led to a transiently greater recall of cross-reactive memory B cells. However, the long-term effects differed. Several months after an Omicron infection, memory B cells showed higher neutralization capacity against both the original Wuhan-1 strain and the BA.1 variant. But this came at a cost: these cross-reactive memory B cells from infected individuals displayed less breadth and were less effective against the more distant BA.2.86 lineage compared to cells from uninfected individuals. This demonstrates how repeated exposures to evolving antigens can shape, and in some ways narrow, the long-term memory B cell repertoire.

If you only have time for one paper this week, make it the study in JACI: In Practice on social determinants of health in hereditary angioedema [2]. It's a powerful reminder that patient outcomes are shaped not just by their biology and our treatments, but by socioeconomic factors that determine their access to care and ability to manage their disease.

Here are the key takeaways from this week in Allergy & Immunology. First, when considering discontinuing biologics for severe asthma, be aware that baseline eosinophilia, persistent sputum during therapy, and stopping due to poor response are major risk factors for exacerbation. Careful, phenotype-driven patient selection is key [7]. Second, in patients with hereditary angioedema, social and economic factors significantly impact outcomes. Patients who are Black or from lower-income households have higher rates of emergency department use and may have less access to specialist care, warranting targeted interventions to ensure equity [2]. Third, for patients with cashew allergy, counsel them that reaction thresholds can be extremely low—much lower than for peanut—and that co-allergy to pistachio is a significant risk factor for having a lower threshold [1]. And finally, in refractory allergic rhinitis, steroid resistance may be driven by an IL-17A-mediated pathway involving the SPRR2A-CSTA axis, which could serve as a future biomarker to guide therapy away from corticosteroids in select patients [3].

That's your roundup for This Week in Allergy & Immunology. The full transcript and references are available on the episode page in your AudioScholar library. This is an AI-curated summary — for clinical decisions, always consult primary sources and current guidelines. See you next week.

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This is an automated summary generated by artificial intelligence, which can make mistakes. Always review the original source materials.