Interpretation

Abnormal mitogen stimulation test results are indicative of impaired T-cell function if T-cell counts are normal or only modestly decreased. If there is profound T-cell lymphopenia, there could be a dilution effect with under-representation of T cells within the peripheral blood mononuclear cell population that could result in lower T-cell proliferative responses. However, this is not a significant concern in the flow cytometry assay since acquisition of additional cellular events during analysis can compensate for artificial reduction in proliferation due to lower T-cell counts.

There is no absolute correlation between T-cell proliferation in vitro and a clinically significant immunodeficiency, whether primary or secondary, since T-cell proliferation in response to activation is necessary, but not sufficient, for an effective immune response. Therefore, the proliferative response to mitogens can be regarded as a more specific, but less sensitive, test for the diagnosis of infection susceptibility.

No single laboratory test can identify or define impaired cellular immunity on its own.

Controls in this laboratory and most clinical laboratories are healthy adults. Since this test is used for screening and evaluating cellular immune dysfunction in infants and children, it is reasonable to question the comparability of proliferative responses between healthy infants, children, and adults. One study has reported that the highest mitogen responses are seen in newborn infants with subsequent decline to 6 months of age and a continuing decline through adolescence to half the neonatal response.(9) In an in-house evaluation of 43 pediatric specimens (of all ages) with adult normal controls, only 21% and 14% were below the tenth percentile of the adult reference range for pokeweed and phytohemagglutinin, respectively. A comment will be provided in the report documenting the comparison of pediatric results with an adult reference range and correlation with clinical context for appropriate interpretation.

Without obtaining formal pediatric reference values, it remains a possibility that the response in infants and children can be underestimated. However, the practical challenges of generating a pediatric range for this assay necessitate comparison of pediatric data with adult reference values or controls.

Lymphocyte proliferation responses to mitogens and antigens are significantly affected by time elapsed since blood collection. Results have been shown to be variable for specimens assessed between 24- and 48-hours post blood collection; therefore, lymphocyte proliferation results must be interpreted with due caution and results should be correlated with clinical context.