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Author

C. Happle

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Open access Jul 2026

Increased high sensitivity C-reactive protein in more severe wheeze/asthma phenotypes in child- and adulthood in ALLIANCE

The relevance of high-sensitivity C-reactive protein (hsCRP), a marker of low-grade systemic inflammation, remains unclear with regard to its association with severity and clinical outcomes in wheeze/asthma. We aimed to assess the role of hsCRP across different phenotypes and severity levels. We studied children with preschool wheeze (≥ 2 episodes), and patients with GINA-defined asthma (school-age/adult) compared with healthy controls (HCs) in the well-characterized ALLIANCE (All Age Asthma Cohort) study. HsCRP was measured (AU5800®-CRP-Latex test) in 944 study participants (pediatric: n = 728; adult: n = 216) at baseline. Age-stratified analyses (age groups 0–5, 6–18, ≥ 18 years) of standardized log10-transformed hsCRP concentrations (age, sex, BMI, site) were performed using univariable tests and regression models. The validated ASSESS score and its dimensions (exacerbations, lung function, inhaled corticosteroids, symptom control) were primary outcomes. Adult patients with asthma showed higher hsCRP than HCs (OR 2.22, 95% CI 1.56–3.24). Across all ages, hsCRP increased with clinical severity of wheeze/asthma. The ASSESS score correlated positively with hsCRP in patients aged ≥ 6 years (R = 0.19, p = 0.007). hsCRP was increased in school-age asthmatics with prior exacerbations (OR 1.37, 95% CI 1.01–1.87), and in adult asthmatics with impaired lung function (R = 0.2, p = 0.013). Inhaled corticosteroid use was associated with lower hsCRP in preschool wheezers (OR 0.66, 95% CI 0.50–0.85) but higher levels in adults (OR 1.99, 95% CI 1.02–4.09). HsCRP was increased in adult asthmatics compared to HCs and was associated with several severity-related clinical characteristics. ICS use was associated with higher hsCRP levels in adults, potentially reflecting greater disease severity, whereas ICS use in preschool wheezers was associated with lower hsCRP levels. These age-dependent effects may mirror varying disease courses across the lifespan and progression of asthma. The association of hsCRP with asthma severity in child- and adulthood may indicate its potential relevance for the course of disease and monitoring clinical outcomes. Future longitudinal studies are needed to assess, whether hsCRP may support therapy monitoring. ClinicalTrials.gov; Pediatric arm: NCT02496468, Registration date: 03 July 2015; Adult arm: NCT02419274, Registration date: 14 April 2015.

Lena Lagally, Lena Ullemeyer, J. Omony et al. · 0 citations
Open access Jul 2026

JN.1-adapted vaccination is associated with readjustment of ancestral memory B cells toward neutralization within the JN.1 antigenic space

The antigenic drift of SARS-CoV-2 toward the JN.1 lineage has prompted the development of variant-adapted COVID-19 booster vaccines. However, these boosters are thought to primarily recall pre-existing memory B cells (MBC), raising concerns about their ability to realign the immune response in highly pre-exposed populations. Here we analyze antibody and B cell responses in pre-exposed individuals (n = 42; median 4.5 prior COVID-19 vaccinations; 90% with at least one prior SARS-CoV-2 infection) following vaccination with a JN.1-adapted mRNA vaccine. Vaccination is associated with increased IgG binding and enhanced neutralization of JN.1 and related descendant variants. Longitudinal profiling of antigen-specific MBC shows that Wu01-only and Wu01/JN.1 cross-reactive cells remain dominant, while JN.1-only cells modestly increase by day 21. Single-cell RNA-sequencing of antigen-specific MBC in a representative sub-cohort (n = 7), combined with functional monoclonal antibody analyses, demonstrates that somatic hypermutation (SHM) drives intra-clonotype specialization toward improved JN.1 binding and neutralization. These findings indicate maturation of pre-existing, class-switched MBC rather than substantial de novo recruitment of naïve B cells. In conclusion, JN.1-adapted booster vaccination is associated with refinement of pre-existing MBC repertoires toward the JN.1 antigenic space and with enhanced neutralization of contemporary and antigenically proximate variants. Because of the continuous evolution of SARS-CoV-2, pre-existing immune responses may not be as effective against new viral variants. Here the authors investigate whether B cell responses to ancestral SARS-CoV-2 are stimulated by JN.1-adapted booster vaccines and propose that there is somatic hypermutation of existing B cell clones rather than de novo generation from naive B cells.

M. Stankov, Matthias Bruhn, M. Hoffmann et al. · 0 citations