Serum free light chains in a racially diverse population including African Americans and populations from South Africa

Detection of light chain (LC) monoclonal gammopathies (MGs) traditionally relies on serum free LC (FLC) κ, λ, and their ratio (κ/λ) reference ranges based on a mostly White population. We investigated FLC values in a racially diverse population by screening 10 035 individuals for heavy chain MG, identifying 9028 negative cases whose FLC were measured. Participants included 4149 from the PROMISE study (United States, n = 2383; South Africa, n = 1766) and 4879 from the Mass General Brigham Biobank, with 44% self-identifying as Black. Using standard FLC reference ranges, 1074 of 10 035 individuals (10.7%) were diagnosed with LC monoclonal gammopathy of undetermined significance (MGUS), with 99% being κ-restricted. In the United States, 14.8% of Black and 4% of White individuals were diagnosed (P < .01). Among US participants of African (AFR) and European (EUR) genetic ancestry, 14.4% AFR and 2.9% EUR were diagnosed (P < .01). Among South Africans (100% Black), 27.8% were diagnosed using standard ranges. To avoid overdiagnosis, we propose a new κ/λ ratio reference range (0.686 to 2.10) for populations of AFR descent with normal renal function, with standard values for κ and λ being 7.97 to 77.50 mg/L and 6.20 to 49.20 mg/L, respectively. This reduces LC-MGUS overdiagnosis by 91% (10.7% vs 0.97%). Using the new reference, LC-MGUS accounts for 8.8% of MGUS cases, with 74% being κ-restricted, consistent with LC myeloma rates. These findings highlight the importance of basing disease definitions, such as MGUS, on diverse populations. Adopting our proposed FLC reference values would reduce MGUS overdiagnosis among Black individuals, avoiding unnecessary financial, psychological, and medical consequences. This study includes data from NCT03689595.

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Publication Details

Journal
Blood
Published
2024-11-21
DOI
https://doi.org/10.1182/blood.2024026078
Citations
7
Primary Topic
vaccines and immunoinformatics approaches
Type
article
Field-Weighted Citation Impact
1.64
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article

Serum free light chains in a racially diverse population including African Americans and populations from South Africa

Derek Troske, Gad A. Getz, Grace Fleming, Maya Inez Davis et al.
7 citations
Blood
vaccines and immunoinformatics approaches
1.64
article

Serum free light chains in a racially diverse population including African Americans and populations from South Africa

Derek Troske, Gad A. Getz, Grace Fleming, Maya Inez Davis, Jean-Baptiste Alberge, Elizabeth D. Lightbody, Irene M. Ghobrial, Sabine Allam, Wenlong Carl Chen, Lindokuhle Goqwana, Habib El‐Khoury, David Jungpa Lee, Mark C. Perkins, Jacqueline Perry, Lorenzo Trippa, Natalie Smyth, Luca Bertamini, Ciara Murphy, Dhananjay Sakrikar, Catherine R. Marinac, Maureen Joffe, Julia Colchie, Sungjae Kim, Nikhil Munshi, Stephen Harding, Elizabeth W Karlson, Kenneth C. Anderson, Vinitha Philip
article en
7 citations

Abstract

Detection of light chain (LC) monoclonal gammopathies (MGs) traditionally relies on serum free LC (FLC) κ, λ, and their ratio (κ/λ) reference ranges based on a mostly White population. We investigated FLC values in a racially diverse population by screening 10 035 individuals for heavy chain MG, identifying 9028 negative cases whose FLC were measured. Participants included 4149 from the PROMISE study (United States, n = 2383; South Africa, n = 1766) and 4879 from the Mass General Brigham Biobank, with 44% self-identifying as Black. Using standard FLC reference ranges, 1074 of 10 035 individuals (10.7%) were diagnosed with LC monoclonal gammopathy of undetermined significance (MGUS), with 99% being κ-restricted. In the United States, 14.8% of Black and 4% of White individuals were diagnosed (P < .01). Among US participants of African (AFR) and European (EUR) genetic ancestry, 14.4% AFR and 2.9% EUR were diagnosed (P < .01). Among South Africans (100% Black), 27.8% were diagnosed using standard ranges. To avoid overdiagnosis, we propose a new κ/λ ratio reference range (0.686 to 2.10) for populations of AFR descent with normal renal function, with standard values for κ and λ being 7.97 to 77.50 mg/L and 6.20 to 49.20 mg/L, respectively. This reduces LC-MGUS overdiagnosis by 91% (10.7% vs 0.97%). Using the new reference, LC-MGUS accounts for 8.8% of MGUS cases, with 74% being κ-restricted, consistent with LC myeloma rates. These findings highlight the importance of basing disease definitions, such as MGUS, on diverse populations. Adopting our proposed FLC reference values would reduce MGUS overdiagnosis among Black individuals, avoiding unnecessary financial, psychological, and medical consequences. This study includes data from NCT03689595.

BloodVol. 145(8)
Broad Institute (US), National Health Laboratory Service (ZA), Brigham and Women's Hospital (US), Harvard University (US), University of the Witwatersrand (ZA), Chris Hani Baragwanath Hospital (ZA), University of Chicago (US), Massachusetts General Hospital (US), Dana-Farber Cancer Institute (US), Thermo Fisher Scientific (United Kingdom) (GB), Thermo Fisher Scientific (United States) (US), Center for Cancer Research (US), Thermo Fisher Scientific (Israel) (IL)
Openalex Percentile: Top 16%
vaccines and immunoinformatics approaches
1.64
DOIOpen Access PDFOpenAlex
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