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Medscape
30-07-2025
- Health
- Medscape
T Cells Target Cockroach Allergens in Therapy Extracts
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. Alessandro Sette, DrBiolSci '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. Marie Cavuoto Petrizzo, MD, MSEd 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.
Jordan News
11-03-2025
- Health
- Jordan News
Men Are More Likely to Develop Parkinson's Disease - Jordan News
A new study has revealed that the risk of developing Parkinson's disease (also known as "shaking palsy") is twice as high in men as it is in women, suggesting a potential cause related to a harmless protein in the brain. اضافة اعلان This protein is called PINK1 kinase, and it is typically not harmful; it plays an important role in regulating cellular energy use in the brain. However, the new study shows that, in some cases of Parkinson's disease, the immune system mistakenly treats PINK1 as an enemy and attacks brain cells containing this protein. According to the study, conducted by a team from the La Jolla Institute for Immunology in California and based on blood samples from Parkinson's patients, damage to this protein caused by T-cells in the immune system is more widespread and aggressive in men's brains compared to women's. Immunologist Alessandro Sette, who participated in the study, said, "The sex-based differences in T-cell responses were truly remarkable." He added, "In male Parkinson's patients, we observed a six-fold increase in T-cells targeting brain cells that carry the PINK1 protein, compared to healthy brains. In female patients, there was only a 0.7-fold increase." Researchers pointed out that these findings could help develop treatments to prevent T-cells from attacking the PINK1 protein, thereby protecting brain cells. It's important to note that Parkinson's disease is a neurodegenerative condition that gradually manifests with stiffness, tremors, and slow movement. The disease's symptoms are due to the death of important nerve cells in an area near the brainstem, which are indirectly involved in controlling fine motor skills.
Yahoo
10-03-2025
- Health
- Yahoo
Men Have Higher Risk of Parkinson's, And We May Finally Know Why
The risk of developing Parkinson's disease is twice as high in men as in women, and new research points to a potential reason why: a normally benign protein in the brain. PTEN-induced kinase 1 (PINK1) protein is not normally a threat, and is important in regulating cellular energy use in the brain. However, the new research shows that in some Parkinson's cases, the immune system mistakes PINK1 for an enemy, attacking brain cells that express the protein. According to the study, led by a team from the La Jolla Institute for Immunology in California, the PINK1-related damage done by the immune system's T cells is much more widespread and aggressive in the brains of men than women. "The sex-based differences in T cell responses were very, very striking," says immunologist Alessandro Sette, from the La Jolla Institute for Immunology. "This immune response may be a component of why we see a sex difference in Parkinson's disease." Using blood samples from Parkinson's patients, the researchers tested the response of the T cells in the blood against a variety of proteins previously linked to Parkinson's – finding that PINK1 stood out. In the male Parkinson's patients, the research team noticed a six-fold increase in T cells targeting PINK1-tagged brain cells, compared with healthy brains. In the female Parkinson's patients, there was only a 0.7-fold increase. Some of the same researchers had previously found something similar happening with T cells and the alpha-synuclein protein. However, these reactions weren't common to all Parkinson's brains, which prompted the hunt for more antigens – substances that trigger immune responses. As is always the case with research of this type, once experts know more about how a disease gets started and how it progresses, that opens up new opportunities for finding ways to put a halt to the damage. "We could potentially develop therapies to block these T cells, now that we know why the cells are targeting in the brain," says immunologist Cecilia Lindestam Arlehamn, from the La Jolla Institute for Immunology. Further down the line, being able to spot these PINK1-sensitive T cells in blood samples could lead to Parkinson's disease being diagnosed at an earlier stage – which again helps with treatment and patient support. While we're still waiting to discover a cure for Parkinson's disease, constant progress is being made in understanding the risk factors involved in its development, and new approaches to tackling it. "We need to expand to perform more global analysis of the disease progression and sex differences – considering all the different antigens, disease severities, and time since disease onset," says Sette. The research has been published in the Journal of Clinical Investigation. An Ancient Disease Has Reappeared in The US. This Could Be Why. Daylight Saving Disrupts Millions of Americans. There's a Better Way. This Common Blood Pressure Drug Extends Lifespan And Slows Aging in Animals
