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Published on: December 27, 2016
Analysis of in vitro lymphocyte proliferation as a screening tool for cellular immunodeficiency
Kelly D Stone1, Henry A Feldman, Charlotte Huisman
1Division of Immunology, Children's Hospital Boston, Boston, MA 02115, USA.
Insights
Lymphocyte proliferation assays are useful for screening cellular immunodeficiency. However, concanavalin A (CONA) and tetanus toxoid (TT) were most effective, and the test is not a sensitive predictor of infection risk.
Area of Science:
- Immunology
- Clinical Diagnostics
Background:
- Lymphocyte proliferation assays are standard for detecting cellular immunodeficiency.
- Limited data exists on their screening performance across diverse patient groups.
Purpose of the Study:
- To evaluate the effectiveness of lymphocyte proliferation assays as a screening tool for cellular immunodeficiency.
- To compare the performance of different mitogens and antigens in identifying T cell dysfunction.
Main Methods:
- Retrospective analysis of proliferation assays (1996-2003) using phytohemagglutinin (PHA), concanavalin A (CONA), pokeweed mitogen, tetanus (TT), and diphtheria (DT) toxoids.
- Receiver operating characteristic (ROC) analysis comparing patients with T cell dysfunction to adult controls.
- Correlation of assay results with clinical data.
Main Results:
- Concanavalin A (CONA) demonstrated superior performance over phytohemagglutinin (PHA) in identifying immunodeficient patients.
- Tetanus toxoid (TT) was the second most effective antigen.
- Interpretation methods (raw counts, stimulation index, or simultaneous controls) showed equal performance.
- Combining data from multiple stimulants did not improve assay performance.
Conclusions:
- Lymphocyte proliferation testing is a valuable component of cellular immunodeficiency screening.
- The assay's sensitivity in predicting immune compromise or opportunistic infection risk is limited.
- CONA and TT are the most effective stimulants for this screening purpose.
Abstract:
Measuring lymphocyte response to mitogens and antigens is a mainstay of screening for cellular immunodeficiency. Few reports analyze performance as a screening tool in diverse patient cohorts. We studied proliferation assays performed at Children's Hospital Boston from 1996 to 2003 using mitogens phytohemagglutinin (PHA), concanavalin A (CONA) and pokeweed mitogen, and antigens tetanus (TT) and diphtheria (DT) toxoids, and compared a subset of patients with T cell dysfunction with adult controls using receiver operating characteristic analysis. Results were correlated with clinical data. CONA was superior to PHA in identifying patients with immunodeficiency. TT was second best. Interpretation based on raw CPM, a stimulation index, or reference to simultaneous controls all performed equally. Combining data from multiple mitogens and/or antigens did not enhance performance. Proliferation testing is a useful component of screening for cellular immunodeficiency, but is not a sensitive predictor of cellular immune compromise or risk of opportunistic infection.
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