Warning values of serum total kappa/lambda ratio for M-proteinemia.
Cutoff
K/L
M-proteinemia
Plasma cell monoclonal
ROC
Journal
BMC immunology
ISSN: 1471-2172
Titre abrégé: BMC Immunol
Pays: England
ID NLM: 100966980
Informations de publication
Date de publication:
30 Oct 2024
30 Oct 2024
Historique:
received:
11
03
2024
accepted:
24
10
2024
medline:
31
10
2024
pubmed:
31
10
2024
entrez:
31
10
2024
Statut:
epublish
Résumé
To introduce the serum total kappa/lambda ratio (K/L) in humoral immunity testing reports to improve the detection rate of M-proteinemia. 156 M protein-positive and 5464 M protein-negative samples confirmed by serum immunofixation electrophoresis(sIFE) were accumulated from January 2021 to December 2023 in the First Affiliated Hospital of Soochow University and the contents of immunoglobulins (IgG, IgA, IgM, kappa and lambda) were tested by Beckman IMMAGE800. All the samples were divided into two groups by time: the modeling group and the validation group. The K/L values in the modeling group were analyzed by SPSS 27.0 to get the receiver operating characteristic curve (ROC). Furthermore, a more in-depth analysis was conducted to verify the reliability of the optimal cutoff values in the validation group. In addition, the levels of immunoglobulins of another group including 106 patients with definite diagnosis of monoclonal gammopathy ranging from January 2021 to June 2024 were traced back to improve the diagnostic efficiency. The optimal cutoff values of K/L were 2.31 and 1.43 corresponding to K-type and L-type M-proteinemia respectively by ROC analysis. The sensitivity and specificity were validated as 76.14% and 77.42%. False positives were mainly found in samples with systemic sclerosis (36.84%), hypohepatia (28.71%) and sicca syndrome (27.27%). While false negatives were mainly found in IgA monoclonal gammopathy (38.39%) and IgM monoclonal gammopathy (28.57%). Combining with the detection rules of IgG, IgA and IgM, the sensitivities for the diagnosis of immunoglobulin light chain amyloidosis(AL) and monoclonal gammopathy of undetermined significance(MGUS) can be increased to 83.33% and 85%. K/L > 2.31 and K/L < 1.43 can be used as warning values for M-proteinemia. In addition, the content of the heavy chain in IgA- or IgM-type M-proteinemia may be considered to improve the detection rate.
Sections du résumé
BACKGROUND
BACKGROUND
To introduce the serum total kappa/lambda ratio (K/L) in humoral immunity testing reports to improve the detection rate of M-proteinemia.
METHODS
METHODS
156 M protein-positive and 5464 M protein-negative samples confirmed by serum immunofixation electrophoresis(sIFE) were accumulated from January 2021 to December 2023 in the First Affiliated Hospital of Soochow University and the contents of immunoglobulins (IgG, IgA, IgM, kappa and lambda) were tested by Beckman IMMAGE800. All the samples were divided into two groups by time: the modeling group and the validation group. The K/L values in the modeling group were analyzed by SPSS 27.0 to get the receiver operating characteristic curve (ROC). Furthermore, a more in-depth analysis was conducted to verify the reliability of the optimal cutoff values in the validation group. In addition, the levels of immunoglobulins of another group including 106 patients with definite diagnosis of monoclonal gammopathy ranging from January 2021 to June 2024 were traced back to improve the diagnostic efficiency.
RESULTS
RESULTS
The optimal cutoff values of K/L were 2.31 and 1.43 corresponding to K-type and L-type M-proteinemia respectively by ROC analysis. The sensitivity and specificity were validated as 76.14% and 77.42%. False positives were mainly found in samples with systemic sclerosis (36.84%), hypohepatia (28.71%) and sicca syndrome (27.27%). While false negatives were mainly found in IgA monoclonal gammopathy (38.39%) and IgM monoclonal gammopathy (28.57%). Combining with the detection rules of IgG, IgA and IgM, the sensitivities for the diagnosis of immunoglobulin light chain amyloidosis(AL) and monoclonal gammopathy of undetermined significance(MGUS) can be increased to 83.33% and 85%.
CONCLUSIONS
CONCLUSIONS
K/L > 2.31 and K/L < 1.43 can be used as warning values for M-proteinemia. In addition, the content of the heavy chain in IgA- or IgM-type M-proteinemia may be considered to improve the detection rate.
Identifiants
pubmed: 39478462
doi: 10.1186/s12865-024-00664-6
pii: 10.1186/s12865-024-00664-6
doi:
Substances chimiques
Immunoglobulin kappa-Chains
0
Immunoglobulin lambda-Chains
0
Myeloma Proteins
0
multiple myeloma M-proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
73Informations de copyright
© 2024. The Author(s).
Références
Murray DL, Puig N, Kristinsson S, et al. <ArticleTitle Language="En">Mass spectrometry for the evaluation of monoclonal proteins in multiple myeloma and related disorders: an International Myeloma Working Group Mass Spectrometry Committee Report[J]. Blood cancer J. 2021;11(2):24.
doi: 10.1038/s41408-021-00408-4
pubmed: 33563895
pmcid: 7873248
Gao Y, Feng X et al. Prognostic significance of serum monoclonal proteins based on immunofixation electrophoresis in B-cell non-Hodgkin lymphoma [J]. Ann Hematol Published online Dec 20, 2023.
Huang J, Chan SC, Lok V, et al. The epidemiological landscape of multiple myeloma: a global cancer registry estimate of disease burden, risk factors, and temporal trends. Lancet Haematol. 2022;9(9):670–7.
doi: 10.1016/S2352-3026(22)00165-X
Wang W, Li J, Yang Y et al. Update on the outcome of M-protein screening program of multiple myeloma in China: A 7-year cohort study. Cancer Med Published online Dec 22, 2023.
Seesaghur A, Petruski-Ivleva N, Banks VL, et al. Clinical features and diagnosis of multiple myeloma: a population-based cohort study in primary care[J]. BMJ open. 2021;11(10):52–9.
doi: 10.1136/bmjopen-2021-052759
Zhai L, Zhao Y, Peng S, et al. Detection of the value of consecutive serum total light chain (sTLC) in patients diagnosed with diffuse large B cell lymphoma[J]. Ann Hematol. 2016;95(12):1999–2007.
doi: 10.1007/s00277-016-2794-8
pubmed: 27623628
Rajkumar SV. Updated Diagnostic Criteria and Staging System for Multiple Myeloma. Am Soc Clin Oncol Educ Book. 2016;35:e418–23.
doi: 10.1200/EDBK_159009
pubmed: 27249749
Landgren O, Kyle RA, Pfeiffer RM, Katzmann JA, Caporaso NE, Hayes RB, et al. Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study [J]. Blood. 2009;113(541):2–7.
Khwaja J, D’Sa S, Minnema MC, Kersten MJ, Wechalekar A, Vos JM. IgM monoclonal gammopathies of clinical significance: diagnosis and management. Haematologica. 2022;107(9):2037–50. Published 2022 Sep 1.
doi: 10.3324/haematol.2022.280953
pubmed: 35770530
pmcid: 9425303
Pang L, Rajkumar SV, Kapoor P, et al. Prognosis of young patients with monoclonal gammopathy of undetermined significance (MGUS). Blood Cancer J. 2021;11(2):26. Published 2021 Feb 1.
doi: 10.1038/s41408-021-00406-6
pubmed: 33563898
pmcid: 7873268
Lam CW, Chui SH, Leung NW, Li EK, Lai KN. Light chain ratios of serum immunoglobulins in disease. Clin Biochem. 1991;24(3):283–7.
doi: 10.1016/0009-9120(91)80021-T
pubmed: 1908361
Grimaldi LM, Castagna A, Maimone D, et al. Kappa light chain predominance in serum and cerebrospinal fluid from human immunodeficiency virus type 1 (HIV-1)-infected patients. J Neuroimmunol. 1991;32(3):259–68.
doi: 10.1016/0165-5728(91)90196-E
pubmed: 1903402
Keren DF, Schroeder L. Challenges of measuring monoclonal proteins in serum[J]. ClinicalChemistry Lab Med. 2016;54(6):947–61.
BarnidgeDR, Surendra D, Marina RA, et al. Phenotyping polyclonal kappa and lambda light chain molecular massdistributions in patient serum using mass spectrometry[J]. J ProteomeResearch. 2014;13(11):5198–205.
BarnidgeDR, Dispenzieri A, Merlini G, et al. Monitoring free light chains in serum using mass spectrometry[J]. ClinicalChemistry Lab Med. 2016;54(6):1073–83.
Lim SM, Wijeratne N, Choy KW, et al. A review of clinical guidelines, laboratory recommendations and external quality assurance programs for monoclonal gammopathy testing[J]. Crit Rev Clin Lab Sci. 2024;61(2):107–26.
doi: 10.1080/10408363.2023.2257306
pubmed: 37776896
Drayson M, Jennis T, Laketic-Ljubojevic I, et al. Laboratory practice is central to earlier myeloma diagnosis: Utilizing a primary care diagnostic tool and laboratory guidelines integrated into haematology services[J]. Br J Haematol. 2024;204(2):476–86.
doi: 10.1111/bjh.19224
pubmed: 38168756
Pontet F. A data base for 3000 monoclonal immunoglobulin cases and a new classification[J]. Clin Chim Acta. 2005;355(1/2):13–21.
doi: 10.1016/j.cccn.2004.11.038
pubmed: 15820473
Gertz MA. Immunoglobulin light chain amyloidosis: 2018 Update on diagnosis, prognosis, and treatment[J]. Am J Hematol. 2018;93(9):1169–80.
doi: 10.1002/ajh.25149
pubmed: 30040145
Hutchison CA, Cockwell, et al. Quantitative assessment of serum and urinary polyclonal free light chains in patients with type II diabetes: an early marker of diabetic kidney disease[J]. Expert Opin Ther Targets. 2008;12(6):667–76.
doi: 10.1517/14728222.12.6.667
pubmed: 18479214
Rajkumar S, Vincent RA, Kyle, et al. Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance[J]. Blood. 2005;106(3):812–7.
doi: 10.1182/blood-2005-03-1038
pubmed: 15855274
pmcid: 1895159
Kyle RA, Themeau TM, Rajkumar SV, et al. A long-term study of prognosis in monoclonal gammopathy of undetermined significance [J]. N Engl J Med. 2002;346:564–9.
doi: 10.1056/NEJMoa01133202
pubmed: 11856795
Lomas OC, Mouhieddine TH, Tahri S, et al. Monoclonal gammopathy of undetermined significance (MGUS)—Not so asymptomatic after all [J]. Cancers. 2020;12(6):1554.
doi: 10.3390/cancers12061554
pubmed: 32545521
pmcid: 7352603
Nasr SH, Said SM, Valeri AM, et al. The diagnosis and characteristics of renal heavy-chain and heavy/light-chain amyloidosis and their comparison with renal light-chain amyloidosis[J]. Kidney Int. 2013;83(3):463–70.
doi: 10.1038/ki.2012.414
pubmed: 23302715
Tietsche de Moraes Hungria V, Allen S, Kampanis P, Soares EM. Serum free light chain assays not total light chain assays are the standard of care to assess Monoclonal Gammopathies[J]. Rev Bras Hematol Hemoter. 2016;38(1):37–43.
doi: 10.1016/j.bjhh.2015.11.003
pubmed: 26969773
pmcid: 4786779
Yang D, Yuan L, Ma X, et al. Histological study of Bactrian camel cryptorchidism and expression of immunoglobulin λ light chain in the testicular and epididymis of cryptorchid Bactrian camel[J]. Reprod Domest Anim. 2024;59(1):e14512.
doi: 10.1111/rda.14512
pubmed: 38069628