Value of monitoring serum immunoglobulins questioned.

Value of Monitoring Serum Immunoglobulins Questioned Our journal club's review of the recent article by Szczeklik al. (EHP 102:302304) found fault on many levels, especially with the concluding recommendation. It would be neither practical nor useful for workers exposed chronically to PAHs to have serum immunoglobulin levels monitored regularly. The use of cross-sectional data regarding serum immunoglobulin levels for detecting immune competence is not clinically sound. Except in patients with congenital deficiencies, there is no correlation between these levels and resistance to infection. There is no basis to compare mean values within the statistically normal range in the expectation that changes reflect immunosuppression. If humoral immune competence is to be evaluated, a useful test involves assessment of the dynamic response to a particular antigen challenge. This biological function has been shown to diminish following in vitro exposure to benzo[a]pyrene, but there is little basis for linking this effect to cancer consequences. Polycyclic aromatic hydrocarbons are not clinically linked to the development of opportunistic infections, the most significant sign of immune suppression. Even if this type of immune deficit had been shown in these workers, there is no basis to make the assertion that humoral immunocompetence has any role in carcinogenesis. Cancer immune surveillance is most significantly accomplished by tumor-infiltrating and T-cell lymphocytes, especially CD8 cells and the helper CD4 cells. Patients with early and even late-stage cancer usually have normal or elevated levels of total serum immunoglobulin, the opposite effect of Szczeklik's workers. Lastly, the paper's own data refute the routine monitoring of exposure with this biological tool. No correlation with duration or magnitude of exposure was identified among these heavily exposed workers. The published graph of the groups intensely overlapping IgG results provides a strong argument against any use of this test in worker monitoring. Critical scrutiny is necessary before introducing routine clinical tests, especially in workplace health and safety. In the setting described in the Szczeklik paper, expenditures on exposure evaluation and reduction by traditional industrial hygiene methods would be more useful than any biological monitoring. In the clinical arena, education and counseling to decrease the workers astonishing 75% prevalence of active smoking would be essential.


alue of Monitoring Serum Immunoglobulins Questioned
Our journal club's review of the recent article by Szczeklik al.  found fault on many levels, especially with the concluding recommendation. It would be neither practical nor useful for workers exposed chronically to PAHs to have serum immunoglobulin levels monitored regularly. The use of cross-sectional data regarding serum immunoglobulin levels for detecting immune competence is not clinically sound. Except in patients with congenital deficiencies, there is no correlation between these levels and resistance to infection. There is no basis to compare mean values within the statistically normal range in the expectation that changes reflect immunosuppression. If humoral immune competence is to be evaluated, a useful test involves assessment of the dynamic response to a particular antigen challenge. This biological function has been shown to diminish following in vitro exposure to benzo[a]pyrene, but there is little basis for linking this effect to cancer consequences.
Polycyclic aromatic hydrocarbons are not clinically linked to the development of opportunistic infections, the most significant sign of immune suppression. Even if this type of immune deficit had been shown in these workers, there is no basis to make the assertion that humoral immunocompetence has any role in carcinogenesis. Cancer immune surveillance is most significantly accomplished by tumor-infiltrating and T-cell lymphocytes, especially CD8 cells and the helper CD4 cells. Patients with early and even late-stage cancer usually have normal or elevated levels of total serum immunoglobulin, the opposite effect of Szczeklik's workers.
Lastly, the paper's own data refute the routine monitoring of exposure with this biological tool. No correlation with duration or magnitude of exposure was identified among these heavily exposed workers. The published graph of the groups intensely overlapping IgG results provides a strong argument against any use of this test in worker monitoring.
Critical scrutiny is necessary before introducing routine clinical tests, especially in workplace health and safety. In the setting described in the Szczeklik paper, expenditures on exposure evaluation and reduction by traditional industrial hygiene methods would be more useful than any biological monitoring. In the clinical arena, education and counseling to decrease the workers astonishing 75% prevalence of active smoking would be essential.

Gary N. Greenberg
Lane Tippens Occupational Medicine Duke University Medical Center Response Greenberg and Tippens's assertion that measurement of serum immunoglobulins is of little value in testing humoral immunity flies in the face of well-established clinical knowledge. So does the statement that "Except in patients with congenital deficiencies, there is no correlation between these [serum immunoglobulin] levels and resistance to infection." Examples refuting the latter statement include certain forms of late-onset hypogammaglobulinemia, also called common variable immunodeficiency, malnutrition, Epstein-Barr virus infection, and depression of serum immunoglobulins caused by high doses of cyclophosphamide or by corticosteroid use in nonatopic (infectious) asthma. Greenberg and Tippens declare: "there is no basis to compare mean values" between the two groups. Why not? The groups were well matched, differing only with regard to chronic PAH exposure. Mathematical analysis revealed that mean serum IgG and IgA differed with high statistical probability (p<O.Ol) between the groups. Moreover, in the group of coke-oven workers, 21.5% of the subjects had IgG levels <1000 mg/dl, and 5% had <700 mg/dl. Such a distinct depression of serum immunoglobulin would be ofconcern to any clinician.
We have demonstrated for the first time in humans that chronic exposure to high PAH concentrations leads to humoral immunosuppression. Based on this finding, we have suggested that workers exposed chronically to high PAH concentrations should have serum immunoglobulins monitored regularly. A similar conclusion was recently reached by Saboori and Newcombe (1), based on their comprehensive review of the existing evidence of immunotoxic effects of PAH in animal studies. The fact that we have not observed a correlation between the length of exposure and serum immunoglobulin levels does not detract from the value of immunoglobulin monitoring. Other factors that we did not evaluate, such as genetic susceptibility or personal exposure, most likely had a significant effect on the immune response.
We agree with Greenberg and Tippens that there is no proof that immunosuppression, as demonstrated by us, is causally related to the high rate of malignancy among coke-oven workers. We did not make such an assertion, the proof of which would require prospective studies. We share the view of Greenberg and Tippens that cigarette smoking does not promote health and should be counteracted.

Andrew Szczeklik Department of Medicine
Jagiellonian University Cracow, Poland