Establishing reference ranges for lymphocyte proliferation responses to phytohemagglutinin in patients with T cell dysfunction
Abstract
Introduction: The evaluation of lymphocyte proliferation responses is a critical component of the clinical work up for patients with suspected immunodeficiencies. Those with severe combined immunodeficiency (SCID) have consistently low to absent responses (stimulation index, SI) to the mitogen phytohemagglutinin (PHA). However, patients with combined immunodeficiency (CID) have more varied proliferative responses, and are open to a wide range of interpretations.
Aims: To establish lymphocyte proliferation response reference ranges for patients with T cell defects, especially those with CID as well as healthy controls.
Methods: Data was collected retrospectively from charts of patients with a diagnosis of SCID (n = 39), CID (n = 52), or from healthy controls (n = 440). Reference percentiles were calculated using the 95% of the distribution of the test results.
Results: The reference ranges for the control group ranged from 134 to 2220.5, whereas those with CID were distributed between 0.81 and 169.1. Patients with typical SCID had profound low proliferative responses, with SI <5.
Conclusion: Our results highlight the variability of lymphocyte proliferation responses to PHA in patients with CID as well as healthy controls. These reference ranges will assist with the critical interpretation of assay results, particularly when values fall on the extreme end of the range.
Statement of novelty: We provide reference ranges for lymphocyte proliferation responses to PHA from patients with CID and healthy controls.
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REFERENCES
Al-Mousa H., Al-Shammari Z., Al-Ghonaium A., Al-Dhekri H., Al-Muhsen S., Al-Saud B., Arnaout R., Al-Seraihy A., Al-Jefri A., Al-Ahmari A., Ayas M., and El-Solh H. 2010. Allogeneic stem cell transplantation using myeloablative and reduced-intensity conditioning in patients with major histocompatibility complex class II deficiency. Biol. Blood Marrow Transplant. 16:818–823.
Arpaia E., Shahar M., Dadi H., Cohen A., and Roifman C.M. 1994. Defective T cell receptor signaling and CD8+ thymic selection in humans lacking zap-70 kinase. Cell. 76:947–958.
Bonilla F.A. 2008. Interpretation of lymphocyte proliferation tests. Ann. Allergy Asthma Immunol. 101:101–104.
Bousfiha A., Jeddane L., Al-Herz W., Ailal F., Casanova J.L., Chatila T., Conley M.E., Cunningham-Rundles C., Etzioni A., Franco J.L., Gaspar H.B., Holland S.M., Klein C., Nonoyama S., Ochs H.D., Oksenhendler E., Picard C., Puck J.M., Sullivan K.E., and Tang M.L. 2015. The 2015 IUIS Phenotypic Classification for Primary Immunodeficiencies. J. Clin. Immunol. 35:727–738.
Buckley R.H., Schiff R.I., Schiff S.E., Markert M.L., Williams L.W., Harville T.O., Roberts J.L., and Puck J.M. 1997. Human severe combined immunodeficiency: Genetic, phenotypic, and functional diversity in one hundred eight infants. J. Pediatr. 130:378–387.
Dean J.H., Connor R., Herberman R.B., Silva J., Mccoy J.L., and Oldham R.K. 1977. The relative proliferation index as a more sensitive parameter for evaluating lymphoproliferative responses of cancer patients to mitogens and alloantigens. Int. J. Cancer. 20:359–370.
Lyons A.B. and Parish C.R. 1994. Determination of lymphocyte division by flow cytometry. J. Immunol. Methods. 171:131–137.
Merico D., Sharfe N., Hu P., Herbrick J.-A., and Roifman C.M. 2015. RelB deficiency causes combined immunodeficiency. LymphoSign J. 2:147–155.
Nowell P.C. 1960. Phytohemagglutinin: An initiator of mitosis in cultures of normal human leukocytes. Cancer Res. 20:462–466.
Orange J.S., Jain A., Ballas Z.K., Schneider L.C., Geha R.S., and Bonilla F.A. 2004. The presentation and natural history of immunodeficiency caused by nuclear factor κB essential modulator mutation. J. Allergy Clin. Immunol. 113:725–733.
Quah B.J., Warren H.S., and Parish C.R. 2007. Monitoring lymphocyte proliferation in vitro and in vivo with the intracellular fluorescent dye carboxyfluorescein diacetate succinimidyl ester. Nat. Protoc. 2:2049–2056.
Roifman C.M., Somech R., Kavadas F., Pires L., Nahum A., Dalal I., and Grunebaum E. 2012. Defining combined immunodeficiency. J. Allergy Clin. Immunol. 130:177–183.
Sharon N. and Lis H. 2004. History of lectins: From hemagglutinins to biological recognition molecules. Glycobiology. 14:53R–62R.
Somech R. and Roifman C.M. 2005. Mutation analysis should be performed to rule out γc deficiency in children with functional severe combined immune deficiency despite apparently normal immunologic tests. J. Pediatr. 147:555–557.
Stepensky P., Keller B., Buchta M., Kienzler A.K., Elpeleg O., Somech R., Cohen S., Shachar I., Miosge L.A., Schlesier M., Fuchs I., Enders A., Eibel H., Grimbacher B., and Warnatz K. 2013. Deficiency of caspase recruitment domain family, member 11 (CARD11), causes profound combined immunodeficiency in human subjects. J. Allergy Clin. Immunol. 131:477–485.e1.
Yu Y., Arora A., Min W., Roifman C.M., and Grunebaum E. 2009. EdU-Click iT flow cytometry assay as an alternative to [3H]thymidine for measuring proliferation of human and mice T lymphocytes. J. Allergy Clin. Immunol. 123:S87.
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Published In
LymphoSign Journal
Volume 6 • Number 1 • March 2019
Pages: 26 - 30
History
Received: 18 January 2019
Accepted: 20 February 2019
Accepted manuscript online: 25 February 2019
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© 2019.
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MohammadAlsalamah, LindaVong, LorandCimpean, and HarjitDadi. 2019. Establishing reference ranges for lymphocyte proliferation responses to phytohemagglutinin in patients with T cell dysfunction. LymphoSign Journal.
6(1): 26-30. https://doi.org/10.14785/lymphosign-2019-0002
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