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Diagnostic Utility of Immunofixation and Free Light Chain Assay in AL Amyloidosis: A Systematic Review and Meta-analysis
Journal article   Open access   Peer reviewed

Diagnostic Utility of Immunofixation and Free Light Chain Assay in AL Amyloidosis: A Systematic Review and Meta-analysis

Muayad Azzam, Qais Hamarsha, Hassan Kawtharany, Jamil Nazzal, Aseel Alkhader, Tala Khraise, Mohammad M AlMasri, Hadi K Abou Zeid, Iktimal Alwan, Nour Jaber, …
Blood advances
04/14/2026
DOI: 10.1182/bloodadvances.2025019530
PMID: 41979328
url
https://doi.org/10.1182/bloodadvances.2025019530View
Published (Version of record) Open Access

Abstract

In this systematic review, we aimed to assess the sensitivity of serum and urine immunofixation (IFE) and serum free light chain (sFLC) in detecting plasma cell dyscrasia (PCD) associated with light chain (AL) amyloidosis. We searched the literature using PubMed, Embase, and CENTRAL databases since inception through March 2024. We included studies reporting the diagnostic accuracy of IFE and/or sFLC in patients with AL amyloidosis. We used the GRADE approach to assess the certainty of evidence and QUADAS-2 to assess the risk of bias. After deduplication, 29,237 records were screened, and 44 studies (n = 18,071) were included. For the meta-analysis, 28 studies reported sensitivity for SIFE (n = 3,390), 24 studies for UIFE (n = 2,830), 19 studies for SIFE and UIFE (n = 2,819), 21 studies for sFLC ratio (n = 3,678), 6 studies for SIFE and sFLC ratio (n = 372), 3 studies for UIFE and sFLC ratio (n = 242), and 10 studies for all three tests (n = 1,430). Pooled sensitivities were: SIFE 0.68 (95% CI 0.62-0.73), UIFE 0.77 (0.72-0.81), SIFE and UIFE 0.89 (0.84-0.93), sFLC ratio 0.82 (0.78-0.86). When SIFE, UIFE, and sFLC ratio were combined, the sensitivity reached 0.99 (0.96-1.00). The high sensitivity of combining SIFE, UIFE, and sFLC ratio supports their use as a reliable initial testing strategy to raise suspicion for AL amyloidosis and guide decisions regarding future diagnostic modalities.

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