Details

Autor(en) / Beteiligte

• Lam, Leo
• Heron, Campbell
• Aspin, Lisa
• Ha, Leah
• Kyle, Campbell V.

Titel

Change in troponin concentrations in patients with macrotroponin: An in vitro mixing study

Ist Teil von

• Clinical biochemistry, 2020-11, Vol.85, p.43-48

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• •Macrotroponin is commonly identified in clinical specimens on high sensitivity troponin assays.•We examined the analytical interference caused by macrotroponin by addition of troponin standards.•The presence of macrotroponin led to negative analytical interference.•The negative interfering effects of macrotroponin varied between assay and patients.•We describe a model to explain why troponin results may be discrepant between assays. Macrotroponin is a complex formed between endogenous cardiac troponin autoantibodies (cTnAABs) and circulating cardiac troponin (cTn). The potential effect of macrotroponin on current high sensitivity cTn assays has not been fully explored but has recently been identified as a major cause of discrepancy in cTn results between assays. In this study we investigated the effects of mixing troponin (cTn) standards to specimens with and without macrotroponin. Macrotroponin was identified in specimens by a recovery of cTnI < 40% following protein A immunoglobulin depletion. Troponin standards containing cTn-IC and cTn-TIC complexes were mixed with serum samples, with (n = 20) and without (n = 10) the presence of macrotroponin. Specimens were tested for cTn before and after mixing by three commercially available high sensitivity cTn assays. Gel filtration chromatography was carried out on five specimens with macrotroponin and each fraction was analzyed by multiple cTn assays. Following mixing with cTn-TIC standard, all specimens with macrotroponin had a markedly reduced absolute increase in cTnI, indicating negative analytical interference due to macrotroponin. Following mixing with the cTn-IC standard, specimens with macrotroponin demonstrated highly variable changes in cTnI, suggesting significant heterogeneity in macrotroponin complex reactivity between individuals. When the ratio of change, calculated by dividing the absolute change between two cTn assays, was compared between specimens with and without macrotroponin, significant differences were observed (p < 0.001). These findings were supported by variable migration of peak cTn activity on gel filtration chromatography. Macrotroponin leads to assay dependent analytical interference affecting current high sensitivity troponin I assays. Furthermore, endogenously occurring cTnAABs are conformationally specific and the analytical effects vary between assays and individuals.