Recent Intravenous Immunoglobulin Administration Can Lead to Serum Protein Electrophoresis Misdiagnosis

The results of a recent retrospective cohort study highlight the correlation between recent administration of intravenous immunoglobulin (IVIG) and serum protein electrophoresis (SPEP) featuring a false M-spike, suggesting that knowledge of recent IVIG administration could reduce SPEP misdiagnosis and lead to more accurate laboratory diagnostic testing.¹

Intravenous immunoglobulin features plasma pooled from thousands of donors, which can lead to misdiagnosis in serum protein electrophoresis tests. | Image Credit: © angellodeco | stock.adobe.com

IVIG, a pooled preparation derived from thousands of donors, has been known to affect laboratory tests that depend upon the measurement of serum antibodies. In a trial examining whether IVIG impacted anti-HBc serology, the passive transfer of anti-HBc from IVIG products was found to lead to false positives.^1,2

Based on these results, the investigators recommended testing patients for anti-HBc either prior to IVIG administration, 3 months or more following IVIG administration, or utilize tested IVIG products that are free of anti-HBc. IVIG manufacturers include a warning with the product that IVIG usage could carry potential interference and misleading results from serology testing.^1,2

In this current trial, the investigators sought to address whether IVIG administration interferes with the interpretation of SPEP by causing the appearance of a monoclonal spike, referred to as an M-spike.¹

Two electronic sources of medical records were utilized for the study. From a total of 100,350 SPEP performed during the study period, 395 contained the keyword "IVIG" and/or "intravenous immunoglobulin" in the pathologist report, making it eligible for inclusion in the review. Studies were contributed by 353 patients, of which 348 were confirmed to have received IVIG.¹

Of the 348 patients analyzed, 20 (6%) had an abnormal SPEP based on the presence of the keywords “spike, band, monoclonal, and/or gammopathy” in the pathologist report, according to the study investigators. IVIG administration was found to be recent-deemed within 30 days from the serum collection date—in 14 patients.¹

Five patients had a M-spike in the SPEP that was not confirmed to be a true monoclonal gammopathy by a subsequent diagnosis assessment, a false positive rate of 1.4% among the 348 patients with a history of IVIG administration.¹

SPEP is commonly utilized in patients that are suspected to have a plasma cell dyscrasia as well as in a variety of other conditions and features a relatively low financial burden. Although numerous other causes of false M-spikes in SPEP have been reported, this trial for the first time discusses the impact that IVIG administration can have on SPEP false positives.¹

The combination of SPEP and serum immunofixation electrophoresis (SIFE) is very reliable in the diagnosis of monoclonal gammopathies, featuring a sensitivity of 92.7% and specificity of 96.3%. Despite the small false positive rate due to IVIG that was observed in this trial, it remains essential to address this issue to reduce misdiagnosis.¹

SPEP/SIFE, and their reliability, play a huge role in the diagnosis of conditions such as multiple myeloma. Because of this aspect, combined with the large volume of immunology samples run by hospital labs on a consistent basis, any action to reduce misdiagnoses—however small—could make a meaningful impact.¹

The investigators recommend caution to physicians or treatment providers such as pharmacists if a SPEP is ordered without the proper patient background. These individuals are in a key position to take note of recent IVIG treatment and avoid extensive patient workup and unnecessary expenses associated with potential misdiagnosis.¹

In this vein, “there should be an apparent notification in a patient’s chart upon the administration or scheduled administration of IVIG which is easily observable,” so serum tests can be planned around therapy, and be interpreted within the proper context, according to the study authors.¹

REFERENCES

1. Sulaiman A, Caturegli P. Falsely abnormal serum protein electrophoresis after administration of intravenous immunoglobulins (IVIG): A retrospective cohort study. Practical Laboratory Medicine. 2024:e00434. doi:10.1016/j.plabm.2024.e00434

2. Arnold DM, Crowther MA, Meyer RM, et al. Misleading hepatitis B test results due to intravenous immunoglobulin administration: implications for a clinical trial of rituximab in immune thrombocytopenia. Transfusion. 2010;50(12):2577-2581. doi:10.1111/j.1537-2995.2010.02766.x