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

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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Journal
Blood Advances
Published
2026-04-14
DOI
https://doi.org/10.1182/bloodadvances.2025019530
Primary Topic
Amyloidosis: Diagnosis, Treatment, Outcomes
Type
article
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article

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

Angela A. Dispenzieri, Matthew D. Seftel, Jack Khouri, Vaishali Sanchorawala et al.
Blood Advances
Amyloidosis: Diagnosis, Treatment, Outcomes
article

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

Angela A. Dispenzieri, Matthew D. Seftel, Jack Khouri, Vaishali Sanchorawala, Nelson Leung, Antonia Carroll, Muayad Azzam, Naresh Bumma, Aseel Alkhader, Jamil Nazzal, Nitasha Sarswat, Joselle Cook, Reem A. Mustafa, Hira Ghazal Shaikh, Daulath Singh, Maria M. Picken, Deborah Boedicker, Hassan Kawtharany, Faizi Jamal, Iktimal Alwan, Qais Hamarsha, Tala Khraise, Hadi K. Abou Zeid, Nour Jaber, Mohammad M. AlMasri, Alfredo De La Torre, M A Aguirre, Raymond Comenzo, Noel R Dasgupta, Vishal Kukreti, Shahzad Raza
article en

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.

Blood Advances
Boston University (US), Boston Medical Center (US), Tufts Medical Center (US), City Of Hope National Medical Center (US), Loyola University Medical Center (US), Sparrow Health System (US), Cleveland Clinic (US), Mayo Clinic (US), Valparaiso University (US), Universidade Presbiteriana Mackenzie (BR), Sparrow Hospital (US), University of Iowa Hospitals and Clinics (US), Hospital Italiano de Buenos Aires (AR), Princess Margaret Cancer Centre (CA), Cleveland Clinic Lerner College of Medicine (US), University of Chicago (US), St Vincent's Hospital Sydney (AU), Greenfield Research (Canada) (CA), University of Kansas Medical Center (US), Hamilton Medical Center (US), AdventHealth Tampa (US), Physicians' Clinic of Iowa (US), Iowa City Public Library (US), Indiana University School of Medicine, NSCAD University (CA), Wake Forest University (US), The Ohio State University (US), Indiana University – Purdue University Indianapolis (US), Canadian Blood Services (CA)
Openalex Percentile: Top 22%
Amyloidosis: Diagnosis, Treatment, Outcomes
DOIOpen Access PDFOpenAlex
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