Prozone effect of serum IgE levels in a case of plasma cell leukemia

Abstract

We describe a case of multiple myeloma (MM) and secondary plasma cell leukemia (PCL) secreting IgE-kappa immunoglobulin. To our knowledge, only 2 cases of IgE-producing secondary PCL have been reported in the medical literature. In our patient, the only tumor marker available for monitoring the therapeutic response to chemotherapy and allogeneic stem cell transplantation was the quantitative M component at serum protein electrophoresis (SPEP), because serum free light chains were in the normal range, Bence-Jones proteinuria was absent, and quantitative serum IgE levels provided inaccurate and erratic results, due to the prozone effect. This is a laboratory phenomenon that occurs when antigen excess interferes with antibody-based methods requiring immune complex formation for detection. It is important to recognize the presence of a prozone effect, because it can produce falsely normal results, and therefore it could lead clinicians to incorrect assessment of the response to therapy.

Multiple Myeloma, Hyperviscosity, Hemodialysis Filter Clogging, and Antigen Excess Artifact: A Case Report

“…This phenomenon is explained by substantially elevated antigen concentration that exceeds antibody levels, resulting in spuriously low antigen antibody complexes and negative results. The hook phenomenon, as encountered with sFLC, is synonymous to the prozone effect that is reported with intact immunoglobulins [7]. Our patient had spuriously low reported kappa and lambda values.…”

“…The hook phenomenon, as encountered with sFLCs, is synonymous to the prozone effect that is reported with intact immunoglobulins. 7 Our patient had spuriously low reported κ and λ values. This finding likely was secondary to excess κ chain burden, overwhelming the concentration of antibodies and thereby impairing the assay performance.…”

Large Molecule Specific Assay Operation: Recommendation for Best Practices and Harmonization from the Global Bioanalysis Consortium Harmonization Team

“…The examination of supraphysiologically high concentrations of biotherapeutic analyte can help define the region in the dynamic assay range that may be susceptible to false negative results (11)(12)(13) or underrecovery due to hook effect (or prozone). Hook effect can be attributed to a number of factors including high molecular weight species or aggregates associated with high analyte concentrations (14,15), saturation of binding capacity of the critical reagents in the assay by an overwhelming amount of analyte, and interference by binding proteins such as ADA, target, or other antigen (12,13,(16)(17)(18).…”

IgE type multiple myeloma exhibits hypermutated phenotype and tumor reactive T cells

“…As described in earlier publications, aberrant IgE secretion of IgE type MM does not seem to elicit a hyperexcitability syndrome, which we could not observe at any time point in the disease course, despite excessive IgE serum levels. 24 The observed CD8 + T cell hyperexpansion, therefore, appears to be postinfectious, as described above or a consequence of an antitumor immune response. The latter hypothesis is further corroborated by patient-individualized prediction and functional testing of immunogenic neoepitopes.…”