What do serum protein electrophoresis (SPEP) and serum immunofixation electrophoresis (SIFE) detect?

A: The most common and perhaps most important rationale for performing SPEP and SIFE is to detect monoclonal immunoglobulins (MIg). Reporting the status of MIg and other immunoglobulins is therefore essential—but it’s also entirely inadequate. SPEP reflects other aspects of patient health such as acute and chronic inflammation, nephrotic syndrome, cirrhosis, alpha 1 anti-trypsin deficiency, complement consumption, and haptoglobin and transferrin abnormalities. When it comes to the first three of these conditions in particular, it is not uncommon for SPEP findings to be the first indication of their presence. Thus, it is imperative that laboratory medicine professionals and pathologists treat SPEP/SIFE as a clinical pathology consultation and report the results in the context of the individual patient, following review of all clinical and laboratory findings.

What information should labs include when reporting SPEP findings?

SPEP (followed by SIFE, if needed) should document the presence, location, isotype, and concentration of the MIg, if present. Comments about other proteins, especially background immunoglobulins, should be included. If the MIg overlaps a normal protein, generally in the beta region, the combined concentration of the two proteins should be documented along with a statement about the overlap. Preliminary studies show that techniques to deplete the contribution of normal beta proteins to MIg could enable more accurate determination of MIg concentration, which in turn could improve the diagnosis of light chain predominant multiple myeloma (MM) (Lab Med 2020; doi:10.1093/labmed/lmaa057). Reporting Hevylite measurement, however, has not been shown to add value.

On first SPEP examination, labs should notify the provider via email if an MIg is detected and a review of the clinical record indicates that a MIg disorder is not under consideration. This is to ensure that the finding does not go unnoticed, especially in ambulatory patients. Simultaneous notification of the hematologist/oncologist and hematopathologist should also be considered.

When should SIFE be performed in addition to SPEP?

With or without an order from a clinician, reflex SIFE should be performed on first SPEP examination if an MIg is noted or suspected, abnormality is noted in one of the normal proteins in the beta or alpha region, or if hypogammaglobinemia is noted. Other reasons include if clinical records indicate lytic bone lesions, osteoporosis and pathological fracture, undiagnosed hypercalcemia, undiagnosed neuropathy, history of lymphoid malignancy, autoimmune disorder, hematopoietic or solid organ transplantation, or amyloidosis. If SIFE is not performed on first or subsequent SPEP examination, a statement to that effect should be included in the report. It is also worth noting that it is perfectly acceptable not to perform SIFE if there is no valid indication, even if a clinician does order it.

Monitoring of MIg in patients with monoclonal gammopathy of undetermined significance or smoldering MM does not warrant repeat SIFE after the first examination. In these cases, reporting the concentration of the MIg is sufficient. The same holds true for patients being treated for MM. However, SIFE is warranted in MM patients if testing following treatment does not reveal an MIg on SPEP, as SIFE is more sensitive.

What else should labs consider when reporting SPEP/SIFE findings?

All cases of light chain myeloma are detectable with urine protein electrophoresis (UPEP) and urine immuno-fixation electrophoresis (UIFE). If UPEP and UIFE are performed at about the same time as SPEP and SIFE, it is useful to include the results of both examinations in the reports for SPEP and UPEP.

Additionally, apparent MIg seen in patients treated with daratumumab and elotuzumab warrants special consideration, as does the emergence of oligoclonal bands following hematopoietic stem cells.

Gurmukh Singh, MD, PhD, MBA, is the Walter Shepeard Professor of Pathology at the Medical College of Georgia at Augusta University. +Email: [email protected]