Dissecting Secondary Immunodeficiency: Identification of Primary Immunodeficiency within B-Cell Lymphoproliferative Disorders

Abstract

Distinguishing between primary (PID) and secondary (SID) immunodeficiencies, particularly in relation to hematological B-cell lymphoproliferative disorders (B-CLPD), poses a major clinical challenge. We aimed to analyze and define the clinical and laboratory variables in SID to B-CLPD, identifying overlaps with late-onset PIDs, which could potentially improve diagnostic precision and prognostic assessment. We studied 37 clinical/laboratory variables in 151 patients with SID to B-CLPD. Patients were classified as “Suspected PID Group” when having recurrent-severe infections prior to the B-CLPD and/or hypogammaglobulinemia according to ESID criteria for PID. Bivariate association analyses showed significant statistical differences between “Suspected PID”- and “SID”-groups in 10 out of 37 variables analyzed, with “Suspected PID” showing higher frequencies of childhood recurrent-severe infections, family history of B-CLPD, significantly lower serum Free Light Chain (sFLC) and immunoglobulin concentrations, and lower total leukocyte, and switch-memory B-cell counts at baseline. Rpart machine learning algorithm was performed to potentially create a model to differenciate both groups. The model developed a decision tree with two major variables in order of relevance: sum κ + λ and history of severe-recurrent infections in childhood, with high sensitivity 89.5%, specificity 100%, and accuracy 91.8% for PID prediction. Identifying significant clinical and immunological variables can aid in the difficult task of recognizing late-onset PIDs among patients with SID to B-CLPD, emphasizing the value of a comprehensive immunological evaluation. The differences between “Suspected PID” and SID groups, highlights the need of early, tailored diagnostic and treatment strategies for personalized patient management and follow up.