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Cockroach immunotherapy effectively modulates T-cell responses in asthmatic children, found authors of a small randomized trial in The Journal of Allergy and Clinical Immunology.

They found that immunodominant allergens are preferentially targeted and trigger the strongest modulation regardless of their concentration in treatment extracts.

“In general, immunotherapy works to ameliorate allergic disease, but the mechanisms that afford its efficacy are not well understood,” corresponding author Alessandro Sette, DrBiolSci, of the Center for Vaccine Innovation at the La Jolla Institute for Immunology, La Jolla, California, told Medscape Medical News.

It is unknown whether T-cell responses to immunodominant allergens are more or less sensitive to modulation and whether the allergen abundance in the immunotherapy extract influences T-cell modulation, the authors noted.

To fill these knowledge gaps, Sette and colleagues evaluated CD4+ T-cell reactivity to cockroach allergens in the double-blinded, placebo-controlled, multicenter CRITICAL (Cockroach Immunotherapy in Children and Adolescents) trial of SCIT (subcutaneous allergen immunotherapy).

Sette added that like rodents, cockroaches produce important allergens, particularly in under-resourced urban settings. Strongly associated with asthma onset, progression, severity, and morbidity, cockroach allergy — particularly to the German cockroach (Blattella germanica) — is a significant global health concern.

It affects children and young adults disproportionately, with cockroach allergens detected in 85% of low-income inner-city homes in the U S.

While several studies have identified cockroach allergens based on immunoglobulin E reactivity and correlated sensitization with symptom severity, T-cell responses have been less thoroughly characterized, Sette said. T-cell responses, particularly in those sensitized to cockroach allergens, are typically associated with type 2 T-helper cells (Th2), which play a central role in allergy and asthma, he said.

The study found that down-regulation of Th2 response did not correlate with the abundance of the various allergens in the extract. “This is important because it suggests that variation in extract content should not impact the downregulation of the detrimental Th2 responses,” Sette said.

“Responses from patients who were highly reactive were downregulated about as well as those from less reactive patients, suggesting that patients can benefit regardless of the strength of their allergic responses.” The findings align with immunotherapy studies of other allergens, he noted.

The results suggest room for a more nuanced approach to cockroach SCIT, incorporating allergen immunodominance, individual patient responses, and abundance-based standardization, which has proven successful for other allergens, said Sette.

Study Details

The results emerged from an evaluation of CD4+ T-cell reactivity specific to the main cockroach allergens in the study extract.

During 2018-2022, young participants, aged 8-17, with mild-to-moderate, well-controlled asthma were recruited from 11 sites in urban and under-resourced neighborhoods in Baltimore; Boston; Chicago; Dallas; Denver; Detroit; New York City; Washington, DC; Cincinnati; and St. Louis. All had positive skin and nasal tests to cockroach allergy.

The children were randomized to receive 12 months of cockroach SCIT injection in 26-step dose escalation (n = 20) or placebo (n = 26). Peripheral blood mononuclear cells were isolated at baseline and after 12 months of treatment or placebo. T-cell responses were evaluated for magnitude, cytokine polarization (differentiation), allergen immunodominance, and correlation with allergen content in the cockroach SCIT extract derived from 11 well-defined cockroach allergens.

SCIT modulation was more prominent in participants with the strongest and greatest number of Th2 polarized responses, the study found. Downmodulation was observed against Bla g 5 and Bla g 9, the most dominantly recognized cockroach allergens for the study population. Furthermore, effective modulation was observed independently of the amount of allergen content in the SCIT extract.

Moreover, treatment responsiveness was strongly predicted by baseline immune characteristics, with SCIT modulation more prominent in children with the strongest and most polarized Th2 responses. “Individual variability in allergen recognition patterns may explain different treatment outcomes,” Sette said.

Offering a nonparticipant’s perspective on the study, Allergist/Immunologist Marie Cavuoto Petrizzo, MD, MSEd, associate dean for medical education at the Zucker School of Medicine at Hofstra University in Hempstead, New York, noted that SCIT currently utilizes crude allergen extracts that are not strictly standardized and are highly variable in content. “Consistent with previous literature, in this study SCIT resulted in modulation of T cells — that is, measurable changes in T-cell quantity and quality — and a shift from Th2 response to allergens to a Th1 response,” she told Medscape Medical News.

“What is novel is the determination that the most significant downmodulation occurred against Bla g 5 and Bla g 9 allergens, which are more frequently recognized by T cells. These allergens are immunodominant but in low abundance in the extracts used during SCIT.”

Since immunodominance varies between individuals, Cavuoto Petrizzo added, “by identifying immunodominant allergens as key targets for modulation, even at low concentrations, it may be possible to develop more effective immunotherapies that prioritize these components. This targeted approach could lead to improved treatment outcomes in cockroach-allergic asthmatic patients.” And while this study focused on cockroach allergy, the findings may have implications for other allergens as well, she said.

This project was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIH). Additional support was provided by NIH’s National Center for Research Resources and National Center for Advancing Translational Sciences. The authors and Cavuoto Petrizzo declared no conflicts of interest.