title: Assessment of the functional integrity of the humoral immune response: the plaque-forming cell assay and the enzyme-linked immunosorbent assay.
abstract: The plaque-forming cell (PFC) assay and enzyme-linked immunosorbent assay (ELISA) appear to have comparable sensitivity and reproducibility for measuring IgM antibody production in mice and rats immunized with sheep red blood cells (sRBCs). Both assays can be manipulated, with respect to the immunizing antigen (e.g., T-dependent vs T-independent antigen), to provide evidence as to which cell type(s) may be adversely affected by a given compound. However, the PFC assay has more utility in dissecting out the target cell(s) involved. Since both the PFC assay and the ELISA may be readily conducted in the rat, it is feasible to incorporate either of these assays into standard acute and repeat dose toxicology studies. This may be accomplished by inclusion of satellite groups in the study. However, it has been suggested that the primary antibody response to sRBCs, as measured by an ELISA, may also be evaluated in the main group of animals in a toxicology study without compromise to the integrity of other toxicological endpoints (e.g., hematology, clinical chemistry, histopathology). Both approaches will provide a more extensive delineation of the safety profile of a drug or chemical. The latter approach will also reduce the number of animals needed and the cost of the study.
authors.affiliation: Division of Anti-inflammatory, Analgesic, and Ophthalmic Drug Products, Food and Drug Administration, 5600 Fishers Lane, HFD-550, Rockville, Maryland 20857, USA. wilsonsu@cder.fda.gov
authors.forename: S D
authors.initials: SD
authors.lastname: Wilson
authors.forename: A E
authors.initials: AE
authors.lastname: Munson
authors.forename: B J
authors.initials: BJ
authors.lastname: Meade
mesh_terms: D000818:Animals; D000917:Antibody Formation; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods* / Q000706:statistics & numerical data; D004912:Erythrocytes / Q000276:immunology; D005069:Evaluation Studies as Topic; D006462:Hemolytic Plaque Technique / Q000706:statistics & numerical data; D006801:Humans; D007114:Immunization; D007075:Immunoglobulin M / Q000096:biosynthesis; D051379:Mice; D051381:Rats; D012680:Sensitivity and Specificity; D012756:Sheep; D014116:Toxicology / Q000379:methods
chemical_list: D007075:Immunoglobulin M