SIMPATHY Study: Specific Antibody Response to Typhim Vi Polysaccharide as a Surrogate Marker of Infectious Risk in Secondary Immunodeficiency Associated with B Cell Cancer

Abstract Recurrent and severe infections represent a major cause of morbidity and mortality of secondary immunodeficiency (SID) associated with B-cell lymphoproliferative syndromes (B-CLPD). Nevertheless, immunological evaluation and prophylactic interventions are often delayed until infectious complications occur. Early vaccination is therefore relevant not only because it provides protection during the initial phases of B-CLPD, but also because it enables the identification of patients at higher risk of infection. In this context, assessment of antigen-specific humoral response has been proposed as a useful biomarker for identifying patients with greater clinical vulnerability. We conducted SIMPATHY (Secondary Immunodeficiency Multicentric study on the Antibody Production to Typhi vaccine), a multicentre, retrospective, observational study including 128 individuals with B-CLPD, classified according to the presence or absence of severe and/or recurrent infections, as well as healthy controls. Specific IgG antibody responses to Streptococcus pneumoniae (13-valent conjugate, Prevenar), Salmonella typhi (Typhim Vi), and tetanus toxoid vaccines were assessed at baseline and 4-weeks after vaccination. Among 128 individuals analysed, patients with B-CLPD showed significant immunological and clinical differences compared to healthy controls, particularly in vaccine-specific antibody responses and lymphocyte subsets. B-CLPD patients with recurrent or severe infections exhibited markedly reduced pre-vaccination anti-pneumococcal ( p = 0.03) and post-vaccination anti-pneumococcal ( p = 0.001) and anti- Salmonella typhi Vi titers ( p = 0.1), highlighting impaired vaccine-specific antibody responses as potential predictors of infection risk. An immunological classification identified two subgroups within B-CLPD, predominant antibody defect and combined immune defect, with a trend toward higher respiratory infection rates in the latter, suggesting broader immune dysfunction.