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Letters to the Editor |
Department of Pathology, University of Iowa, and Veterans Affairs Medical Center, Iowa City, IA
aAddress correspondence to this author at: Department of Pathology, University of Iowa, 200 Hawkins Dr., 149 MRC, Iowa City, IA 52242. Fax 319-339-7148; e-mail yashpal-agrawal{at}uiowa.edu.
To the Editor:
The urine immunofixation test is performed to evaluate the presence of Bence Jones proteinuria (monoclonal free light chains in urine) in patients with multiple myeloma or other lymphoproliferative disorders. The commonly used Bence Jones proteinuria detection assay from Sebia Electrophoresis contains 5 antisera: a trivalent cocktail consisting of antibodies directed against the
,
, and µ heavy chains (GAM); 2 antisera detecting both free and bound
(F+B
) and
(F+B
) light chains; and 2 antisera detecting only the free
(F
) and
(F
) light chains of immunoglobulins.
The rationale for using the F
and F
antisera is that they specifically detect the urinary free
and
light chains that may have nephrotoxic potential (1). This is in contrast to the F+B
and F+B
antisera, which react not only with the free light chains, but also with the "bound" light chains in the intact monoclonal immunoglobulin molecule. We compared the reactivities of the F+B
and F+B
antisera with those of the free light chain antisera in the urine immunofixation test.
After concentration of the urine and subsequent electrophoresis on high-resolution agarose gels, immunofixation was done according to the instructions of the manufacturer (Sebia Electrophoresis). We examined 202 consecutive urine immunofixation gels that showed monoclonal reactivity with any of the 5 antisera in the Sebia Bence Jones Proteinuria assay. The reactivity patterns of the 5 antisera were recorded, and the intensity of the monoclonal band in the F+B
or F+B
lane was compared visually with that in the F
or F
lane, respectively.
The most striking observation was that in 144 of 202 cases, the F
or F
bands were detectable but were much lower in intensity than those in the F+B
or F+B
lanes (Table 1
). In 2 of 202 cases, the bands were of equal intensity with both antisera (F
/
and F+B
/
). In no case was the F
or F
staining more intense than that obtained with the corresponding F+B antiserum. Furthermore, in 33 of 202 cases, the F+B
and F+B
lanes showed monoclonal light chains (i.e., true Bence Jones proteinuria) without accompanying reactivity with the GAM antisera or with the F
or F
antiserum. Therefore, if the intention is to solely identify monoclonal protein in urine, it would appear that use of the F
and F
antisera does not offer any additional information over the F+B
and F+B
antisera. In fact, 16% of patients with likely Bence Jones proteinuria were missed by the F
and F
antisera. The argument that the F+B
/
antisera are not specific for Bence Jones proteinuria but also react with light chains in the intact immunoglobulin molecule must be tempered with our observations that the detection rates with the present F
/F
reagents from Sebia appear to be quite low.
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Only 11% of cases showed a monoclonal heavy chain (GAM positivity) with an accompanying light chain by F+B antisera and no reactivity with the F
and F
antisera. Even in this 11% of cases (of intact monoclonal immunoglobulins), an accompanying small amount of Bence Jones proteinuria cannot be excluded because the detection rates with the F
and F
reagents were much lower than those with the F+B light chain reagents. Therefore, in most cases (>89%), monoclonality with the F+B light chain antisera signified the presence of Bence Jones proteinuria with or without the presence of additional intact immunoglobulins. Clinical pathologists should reevaluate the utility of the currently available F
and F
antisera reagents in the urine immunofixation test.
References
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