The anion gap and routine serum protein measurements in monoclonal gammopathies.

BACKGROUND AND OBJECTIVES: An abnormal anion gap and an increased total protein and globulin are clues to the diagnosis of monoclonal gammopathy. We explored the utility of these markers in IgG, IgA, IgM, and free light chain monoclonal gammopathies. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The anion gap, Na(+) - (Cl(-) + HCO(3)(-)), corrected for hypoalbuminemia, was calculated in patients with monoclonal gammopathies. Exclusion criteria were serum calcium >10.5 mg/dl and/or creatinine >2 mg/dl. RESULTS: Among 287 patients, 242 remained after applying exclusion criteria (109 IgG, 64 IgA, 21 IgM, and 48 light chain); 36% of 242 patients required correction for hypoalbuminemia. The anion gap was decreased (<10) in 22% of IgG and increased (>15) in 31% of IgA monoclonal gammopathies. IgM did not affect the gap. In light chain gammopathies, the anion gap showed no consistent trend (15% increased, 17% decreased). Mean clonal IgG, IgA, and IgM concentrations were 10-fold higher than mean clonal free light chain concentrations in the respective monoclonal gammopathies (P < 0.001). These paraprotein level disparities were reflected in significantly increased mean serum total protein and globulin concentrations in IgG, IgA, and IgM versus free light chain monoclonal gammopathies, where mean total protein and globulin levels were within normal limits (P < 0.001). CONCLUSIONS: The anion gap was significantly altered in IgG and IgA monoclonal gammopathies, but it was not a sensitive tool for suspecting the diagnosis. In light chain monoclonal gammopathies, the anion gap, total protein, and globulin did not provide reliable diagnostic clues.

Comparison of three enzyme-linked immunosorbent assays for detection of immunoglobulin g antibodies to tetanus toxoid with reference standards and the impact on clinical practice.

Accurate determination of the concentrations of immunoglobulin G (IgG) antibody to tetanus toxoid is important in order to evaluate the immunogenicity of tetanus toxoid vaccines, determine immune competence in individual patients, and measure the prevalence of immunity in populations. The performance of three commercially available enzyme-linked immunosorbent assays (ELISAs) for IgG antibodies to tetanus toxoid were evaluated. Serially diluted NIBSC 76/589 and TE-3 human tetanus IgG immunoglobulin international reference standards were analyzed in quadruplicate using ELISAs manufactured by The Binding Site, Inc. (VaccZyme); Scimedx; and Euroimmun. In addition, IgG antibodies to tetanus toxoid were measured in 83 deidentified serum specimens using each manufacturer's ELISA. Each ELISA provided linear results when evaluated with the reference preparations. The Binding Site ELISA provided results that closely corresponded to the reference preparations (y=1.09x-0.08), whereas the Scimedx ELISA gave results that were consistently lower (y=0.21x-0.07) and the Euroimmun ELISA gave results that were consistently higher (y=1.5x+0.30) than the reference preparation concentrations. Using the recommended cutoff for each ELISA (<0.10 IU/ml), the overall agreement of all of the ELISA methods was 78%. Three of eighty-three (3.6%) human serum samples demonstrated inadequate immunity with all three assays. The Binding Site ELISA yielded nonprotective antibody concentrations in only these 3 samples, whereas 19 samples (22.9%) according to the Scimedx ELISA and 6 samples (7.2%) according to the Euroimmun ELISA demonstrated nonprotective concentrations. The performance characteristics of ELISAs for tetanus immunoglobulin titers were manufacturer dependent, and the differences translated into important disparities in reported results.