Immune Cell Function
Clinical Use
- Monitor cell-mediated immunity in immunosuppressed individuals
Clinical Background
Cell-mediated immunity is expressed by T-lymphocytes through direct cytotoxicity and the release of lymphokines. The functions of cell-mediated immunity include the destruction of fungi and tumor cells and the elimination of viral infections. In addition, cell-mediated immunity is responsible for graft-versus-host disease in allograft recipients.
Transplant recipients generally require prolonged treatment with immunosuppressive agents to prevent rejection of the allograft. Correct dosing of immunosuppressives is critical. Over-medicating may leave the individual susceptible to infections or lead to drug toxicity, while under-dosing can lead to shortened graft survival due to the immune response to the transplanted tissue.1,2 Although levels of immunosuppressive drugs are routinely monitored, they do not always correlate with the degree of immunosuppression.1,2Additionally, many current in vitro methods used to study cell-mediated immunity (eg, cytokine production and lymphoproliferation) are unsuitable for clinical practice because they require long turnaround times or are unreliable at predicting graft rejection.2
The Immune Cell Function assay measures the increase in intracellular ATP production that occurs in T-lymphocytes within 24 hours of stimulation by antigens or mitogens.3 Retrospective studies indicate that this ATP level correlates with T-lymphocyte activity and, consequently, cell-mediated immune function4-6; thus, ATP measurement appears to be a useful clinical indicator of cell-mediated immune function.
Individuals Suitable for Testing
- Individuals receiving immunosuppressive therapy
Method
- Phytohemagglutinin stimulation of lymphocyte ATP production
- Magnetic separation of CD4-positive T-lymphocytes
- Chemiluminescent measurement of ATP level
- Analytical sensitivity: 1 ng/mL
- Analytical specificity: ATP produced by CD4-positive T-lymphocytes
- ImmuKnow®, Lymphocyte Stimulation (not to be confused with Lymphocyte Antigen Stimulation)
Reference Range
Table. An ATP level of 226 to 524 ng/mL, for example, reflects a moderate immune response.6 This assay is not designed to predict adverse events. However, in a meta-analysis of retrospective studies including 504 recipients of solid organ transplants, patients maintained at an ATP level between 130 and 450 ng/mL were at minimal risk of adverse events; only 5% of recipients within this range had either rejection or infection.4 The lowest risk for both rejection and infection, established as the intersection of the relative risk curves, was achieved at an ATP level of 280 ng/mL.4
This assay does not directly quantify the level of immunosuppression. Results may be unreliable in some patients immediately following transplantation because of immune system instability caused by surgical trauma, anesthesia, transfusion, immunosuppressive therapy, or very low CD4 count.4 Results should be used in conjunction with clinical presentation, medical history, and other clinical indicators when establishing the immune status of a patient.
References
- Kowalski R, Post D, Schneider M, et al. Immune cell function testing: an adjunct to therapeutic drug monitoring in transplant patient management. Clin Transplant. 2003;17:77-88.
- Schulick RD, Weir MB, Miller MW, et al. Longitudinal study of in vitro CD4+ helper cell function in recently transplanted renal allograft patients undergoing tapering of their immunosuppressive drugs.Transplantation. 1993;56:590-596.
- Sottong PR, Rosebrock JA, Britz JA, et al. Measurement of T-lymphocyte response in whole-blood cultures using newly synthesized DNA and ATP. Clin Diagn Lab Immunol. 2000;7:307-311.
- Kowalski RJ, Post DR, Mannon RB, et al. Assessing relative risks of infection and rejection: a meta-analysis using an immune function assay. Transplantation. 2006;82:663-668.
- Zeevi A, Britz JA, Bentlejewski CA, et al. Monitoring immune function during tacrolimus tapering in small bowel transplant recipients. Transpl Immunol. 2005;15:17-24.
- ImmuKnow®: Cylex® Incorporated Immune Cell Function Assay [package insert]. Columbia, MD: Cylex®Incorporated; 2007.
