B265 The mTOR Pathway is Activated in a Subset of MM and Correlates with High B2-microglobulin

Autor: T Guglielmelli, R Merlini, S Cappia, E Giugliano, E Bacillo, F Gay, A Berruti, M Papotti, G Saglio, A Palumbo
Rok vydání: 2009
Předmět:
Zdroj: Clinical Lymphoma and Myeloma. 9:S118
ISSN: 1557-9190
DOI: 10.1016/s1557-9190(11)70696-5
Popis: Introduction: In multiple myeloma (MM), measurement of IgG paraprotein by serum protein electrophoresis (SPE) densitometry might be affected by changes in plasma volumes and by the saturation of the FcRn recycling receptor; analysis of IgG /IgG ratios could correct for these variations. Novel nephelometric assays utilizing antibodies that recognize junctional conformational epitopes on IgG heavy and light chains have been developed. Here we report the use of these assays in the diagnosis and monitoring of multiple myeloma patients. Materials and Methods: IgG /IgG ratios were measured in 109 blood donor sera to generate a normal range. Archived MM sera collected in Medical Research Council MM trials were analyzed. 71 IgG and 15 IgG patient sera were analyzed at presentation, with serial sample analysis being completed on 7 patients (4 IgG : 3 IgG ). Monoclonal proteins were also assessed using immunofixation (IFE), SPE ( Sebia HYDRASYSTM) and total IgG (Dade Behring). Results and Discussion: Median and 95% ranges for the normal sera were IgG 7.76 g/L (4.23-12.18), IgG 4.00 g/L (2.37-5.91), and IgG /IgG 1.97 (1.26-3.21). Summation of IgG and IgG correlated well with total IgG in all samples tested (r2 = 0.911). All MM presentation sera had abnormal IgG /IgG ratios and/or elevated concentrations of the involved immunoglobulin. In 7 patients followed through the course of treatment, analysis of IgG /IgG ratios accurately reflected clinical assessments. In some instances, IgG /IgG ratios were more sensitive at detecting residual disease than IFE. Furthermore, there were greater ranges of change in IgG /IgG ratios seen during response and relapse than in either intact immunoglobulin measurement or SPE densitometry. Conclusion: Hevylite IgG and IgG immunoassays provide a quantitative method of diagnosing and monitoring disease in MM patients. IgG / IgG ratio analysis matched sensitivity of IFE and SPE densitometry and in some cases proved a more sensitive marker of disease.
Databáze: OpenAIRE
Externí odkaz: