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

• Published in: Journal of clinical immunology Vol. 45; no. 1; p. 115
• Main Authors: Fogsgaard, Stine Fischer, Todaro, Sonia, Larsen, Carsten Schade, Jørgensen, Charlotte Sværke, Jensen, Jens Magnus Bernth
• Format: Journal Article
• Language: English
• Published: New York Springer US 25.07.2025; Springer Nature B.V
• Subjects: Adult; Antibodies; Antibodies, Bacterial - blood; Antibodies, Bacterial - immunology; Biomedical and Life Sciences; Biomedicine; Blood & organ donations; Blood donors; Capsular polysaccharides; Female; Humans; Immune response; Immune system; Immunoassay; Immunodeficiency; Immunology; Infectious Diseases; Internal Medicine; Male; Medical Microbiology; Middle Aged; Pneumococcal Vaccines - immunology; Polysaccharides, Bacterial - immunology; Practice Guidelines as Topic; Primary immunodeficiencies; Prospective Studies; Serotypes; Streptococcus pneumoniae - immunology; Vaccination; Vaccines; Young Adult; Denmark; United States > US; Clinical guidelines; Diagnostic vaccination; Pneumococcal vaccines; Antibody deficiency; Polysaccharide responsiveness percentile; Primary immunodeficiency
• ISSN: 0271-9142; 1573-2592; 1573-2592
• DOI: 10.1007/s10875-025-01915-w

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.