Rheumatoid Factor Interference in Dual Immunoassays: False-Positive Procalcitonin and CK-MB Results

Immunoassays for procalcitonin (PCT) and CK-MB are critical in diagnosing sepsis and myocardial injury. However, rheumatoid factor (RF), an autoantibody against IgG-Fc, may cause false-positive results by bridging capture and detection antibodies in sandwich immunoassays.

An 81-year-old female with rheumatoid arthritis (RF: 652.0 IU/mL) presented discordant PCT and CK-MB mass results. Interference was investigated via serial dilution, platform comparison (StarPilot immunofluorescence vs. Roche electrochemiluminescence), and RF blocking using IgM-specific inhibitors.

StarPilot assays showed elevated PCT (12.38 ng/mL) and CK-MB mass (96.29 ng/mL), contradicting clinical findings (no infection/cardiac symptoms) and CK-MB activity (12 U/L). Ten-fold dilution reduced PCT/CK-MB by 94% and 93%, respectively. Roche platforms returned normal results (PCT: 0.038 ng/mL; CK-MB: 0.203 ng/mL). Adding IgM-blocking reagent (800 µg/mL) normalized PCT (0.023 ng/mL) and CK-MB (0.323 ng/mL).

High-titer RF simultaneously interferes with PCT and CK-MB immunoassays. Dilution tests, alternative platforms, and RF blocking are essential to mitigate misdiagnosis. Laboratories should implement RF interference protocols for discordant results.