Understanding clinical immunological testing in alleged chemically induced environmental illnesses.

Abstract Some believe that an abnormal immunoregulatory response based on environmental damage to T cells is fundamental to the production of symptoms in patients with alleged “multiple chemical sensitivity” and/or “environmental illness.” According to this theory stimulation of T cells or T cell phenotypic subsets by environmental chemicals results in release of cytokines that can effect appropriate target cells of multiple organ systems, resulting in a wide range of symptoms. This concept is reinforced by frequent media reporting of pollution incidents and environmental disasters plus continued isolated reports of immunologic abnormalities in patients with various forms of alleged environmental illness, multiple chemical sensitivities, or other related syndromes. These include reports of slight perturbations in quantity and function of immunoglobulins, complement and its components, B cells, natural killer cells, T cells, phenotypic T cell subsets, and helper suppressor T cell ratios. There are also reports of increased or decreased interleukin levels including IL-1 and IL-2 or their receptors (IL-2R) in these patients. Such assays are not infrequently performed even though there is no evidence for their diagnostic efficacy in these alleged conditions. It is reasonable, however, to anticipate that with the wide development of assays for many of the interleukins and their receptors, these assays may become important in the future diagnosis of many autoimmune, allergic, neoplastic, and infectious diseases. At this time, however, the induction of environmental illness or multiple chemical sensitivity by exposure to trace levels of environmental “immuno- toxins” is unproven and remains a matter of speculation. The reproducibility of immunologic test abnormalities reported under these conditions has not been documented, and the data have often not been analyzed statistically. Appropriate controls also have not usually been employed, nor have control values been provided in many cases. Without consideration of these factors, a patient might be erroneously diagnosed as having some form of “immune dysregulation,” “environmental immune dysfunction,” or “immunotoxic” syndrome on the basis of only a single panel of cellular immunologic profiles or related immunologic tests illustrating slight deviations from the norm and in the absence of overt disease on physical examination. Consideration must also be given to an understanding of biologic variability and diurnal variations in lymphoid cell numbers in interpreting cellular immunologic profiles. For example, the necessity for age and sex-matched controls, test reproducibility, quantitative versus functional assays, and the significance of major versus minor deviations from the norm must be appreciated. In addition, many other conditions can effect immunologic tests, such as medications, psychologic factors, cigarette smoking, and the presence of concurrent disease, including minor viral infections. All of these variables should be appreciated in test interpretation. Certain clinical indications for analysis of cellular components of the immune system, using flow cytometry, have been provided as guidelines although they are by no means accepted by all groups due to their current incomplete evaluation by the clinical immunology community. These suggested indications are discussed. In this article, attempts are made to outline the various quantitative and functional tests used to assess the immune system, with emphasis on “biomarker” tests to detect possible immune system “damage.” Dangers involved in attempting to make clinical evaluations based on results of isolatedin vitroassessment of quantity or function of immune system cellular and humoral components without considering the results of a good medical history and physical examination, the many pitfalls involved in the tests, and the many confounding variables that affect the tests are emphasized, as well as the need for proper controls. In the case of immunophenotyping, using flow cytometry, the lack of standardization, which is only now under consideration, must also be appreciated.