Reassessing Polysaccharide Responsiveness: Unveiling Limitations of Current Guidelines and Introducing the Polysaccharide Responsiveness Percentile Approach

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J Clin Immunol. 2025 Jul 25;45(1):115. doi: 10.1007/s10875-025-01915-w.

ABSTRACT

BACKGROUND: The assessment of polysaccharide responsiveness via vaccination is pivotal in the evaluation of patients for primary immunodeficiency. However, the applicability of current guidelines provided by the American Academy of Allergy, Asthma & Immunology (AAAAI) has been subject to scrutiny.

METHODS: We conducted a prospective study involving 120 healthy Danish adult blood donors. Antibodies targeting pneumococcal capsular polysaccharide serotypes were quantified using a multianalyte bead immunoassay before and four to eight weeks post-vaccination. Polysaccharide responsiveness in donors was assessed according to AAAAI guidelines.

RESULTS: Remarkably, only a minority of participants (2.5%) demonstrated a normal polysaccharide response per AAAAI criteria. This finding prompted us to advocate for an alternative approach based on percentile rankings relative to a reference population. Polysaccharide Responsiveness Percentile (PRP) was not significantly associated with age, sex, vaccine batch, or the duration between vaccination and antibody measurements in our cohort supporting its robustness, generalizability, and potential for standardized clinical application.

CONCLUSION: Our study unveils significant limitations of the AAAAI guidelines, highlighting the imperative for a more robust and adaptable approach. By introducing a novel PRP assessment method, we aim to enhance the accuracy and reliability of immune function evaluations.

PMID:40711631 | DOI:10.1007/s10875-025-01915-w

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