BLOOD TESTS FOR ALLERGIES

Correspondence BLOOD TESTS FOR ALLERGIES To the Editor: I have read with interest the study made by Szeinbach et al.1 The objective of the study is to compare the precision and accuracy of commercial laboratories’ ability to classify positive and/or negative allergen-specific immunoglobulin (Ig)E results. For valid comparison, 1) classification of samples into positive and negative must be based on the same cut-off concentration; 2) comparison of precision and accuracy must use the same concentration, because precision and accuracy depend on concentrations; and 3) class score comparison must use the same classification system. For in vitro allergy testing, physicians, depending on their need, have been using one of two classification systems: 1) classical radioallergosorbent test (RAST) system that uses a cutoff of 0.35 IU/mL,2 and 2) modified RAST system that uses a cutoff of 0.05 IU/mL.3 The Szeinbach study suffered from three experimental design flaws. 1) The authors mixed the classical and modified systems. Note that the same class score of 0, I, or II means very different concentrations, depending on which classification system was used. 2) Instead of using the same concentration unit for comparison, the authors compared counts per minute used in modified RAST with IU/mL used in ImmunoCap (Pharmacia, Kalamazoo, MI). 3) The authors mixed the two very different cutoff concentrations of 0.35 and 0.05 IU/mL, and compared erroneously the ability of each system to classify negative and positive samples. In a recent study,4 as an attempt to correct for these experimental design flaws, the precision and interlaboratory correlation of specific IgE determination by modified RAST was compared among five laboratories, using reagents provided by Hycor Biomedical (Garden Grove, CA). The following results were observed: 1) interassay precision within laboratory was 4 to 16%; 2) class scores from all five laboratories are in very good agreement, with 97.1 to 99.2% of all samples within one class; 3) linear regression of radioactive counts per minute indicates reproducible slopes bracketing one. The conclusion from this study is that the modified RAST method provides good interlaboratory reproducibility and excellent analytical sensitivity. This recent study supports the contention of experimental design flaws exhibited in the Szeinbach et al study and, therefore, invalidates their conclusions that blood tests for allergies produce variable results. If the authors are truly interested in a scientific and valid comparison, they should have compared ImmunoCap with another quantitative classical RAST method. Both the Hycor radioimmunoassay and enzyme immunoassay assays are cleared by the Food and Drug Administration with the quantitative indication for use. Alternatively, ImmunoCap results can also be reported in modified RAST class scores

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via the alternate score method.2 A valid comparison could be to compare modified RAST with Pharmacia by alternate score method. In conclusion, the study by Szeinbach contains several critical scientific and experimental design flaws. It seems to be a poorly concealed attempt to promote one manufacturer’s product, clearly lacks the quality of science, and ignores experimental design normally expected in a scientific publication of a National Institutes of Health grant application.5 THOMAS M. LI, PhD, FACB Hycor Biomedical Garden Grove, California REFERENCES 1. Szeinbach SL, Barnes JH, Sullivan TJ, Williams PB. Precision and accuracy of commercial laboratories’ ability to classify positive and/or negative allergen-specific IgE results. Ann Allergy Asthma Immunol 2001;86:373–381. 2. Pharmacia Cap System Specific IgE FEIA Directions for Use. Kalamazoo, MI: Pharmacia Upjohn, February 2000. 3. Nalebuff DJ, Fadal RG. The modified RAST assay: an aid in diagnosis and management of allergic disorders. Cont Ed 1979:64. 4. Marinova C, Pratt M, Richardson D, et al. Precision and interlaboratory correlation of specific IgE determinations by modified RAST. J Clin Ligand Assay 2001;24:119 –124. 5. NIH Guide: NINDS Clinical Trial Planning grant, PAR-01–118. Bethesda, MD: NIH; July 25, 2001.

Response: We appreciate the opportunity to comment on Dr. Li’s criticisms of our study on different laboratories’ performances in reporting on allergen-specific IgE measurements. Our publication demonstrated that some laboratories/ tests for specific IgE have precision and accuracy problems. Dr. Li’s comment that classification of samples into positive and negative results should be based on the same cutoff concentration is theoretically correct, but makes the assumption that these various assays measure the same thing with the same efficacy. Our data revealed findings to the contrary. Here differences in scale values (concentrations) were noted and equalized with respect to allergen class cutoff sectors, which put each test’s results on the same playing field. In addition, realizing that differences may be attributed to the interpretation of the cutoff value, we performed a sensitivity analysis by varying the class cutoff value. Dr. Li’s position that comparisons of precision and accuracy depend upon concentration is also tenuous. An assay should be precise and accurate across the entire range of reported results. In our study only one assay demonstrated these properties. His complaint that class score comparisons must use the same classification also assumes that such a thing exists. Our study

ANNALS OF ALLERGY, ASTHMA, & IMMUNOLOGY