event®系统在单克隆伽玛病中的B-350诊断性能

IF 6.3 2区医学 Q1 MEDICAL LABORATORY TECHNOLOGY

Clinical chemistry Pub Date : 2025-10-02 DOI:10.1093/clinchem/hvaf086.736

Gabriella Lakos, Syreeta Allen, Gemma Malin, Cristina Simion, Habib El-Khoury, Julia Colchie, Luca Bertamini, Grace Fleming, Erica Horowitz, Irene Ghobrial, Kaleb McLendon, Zianya Solis, John Roback, Andrew Neish, Sarah Grewal, Ashutosh Wechalekar, David Foureau, Manisha Bhutani, Victor Iliev, Oscar Berlanga

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Methods The study included 1135 patients: 718 with monoclonal gammopathy (215 MM, 152 smoldering MM (SMM), 243 monoclonal gammopathy of undetermined significance (MGUS), 53 Waldenström’s Macroglobulinemia (WM), and 55 AL amyloidosis), and 417 disease controls. Clinical diagnoses were defined per appropriate international guidelines. Except for 20 AL amyloidosis patients, all monoclonal gammopathy patients were from the US population. The monoclonal gammopathy cohort had a 1:1 male/female ratio and was ethnically diverse (341 White; 264 African American/ Black; 43 Asian; 17 Hispanic; 53 unknown). The M-protein was IgG in 359 patients, IgA in 95, IgM in 97, light chain-only in 89, IgD in 2; 64 patients had more than one M-protein, and no M-protein was reported by electrophoretic methods in 9 cases. Two IgA, and one IgM patient had heavy chain identified only. In the disease control patients, the diagnosis of monoclonal gammopathy had been ruled out. Serum samples were analyzed at three testing sites using the EXENT System. Diagnostic sensitivity and specificity were calculated based on categorizing results as positive or negative with the EXENT System. A positive result was defined as the presence of an M protein which was either an intact immunoglobulin (IgG&gt;/=0.359 g/L; IgA&gt;/=0.325 g/L; IgM&gt;/=0.227 g/L) or a light chain-only. These isotype-specific cut-off values were established on samples from 364 apparently healthy US subjects for IgG, IgA and IgM M-proteins using the 95th percentile limit for IgG, and the 99th percentile limit for IgA and IgM. A negative result was defined as no M-protein by the EXENT System; or if intact immunoglobulin M-proteins were present, the concentration was below the corresponding isotype-specific cut-off. Diagnostic sensitivity and specificity with 95% confidence interval (CI) were calculated for each diagnosis (MGUS, SMM, MM, WM and AL amyloidosis) separately, and on the pooled results. Results The overall diagnostic sensitivity for monoclonal gammopathies was 92.6% (CI: 90.5-94.3%). Specifically, diagnostic sensitivity was 90.5% (86.2-93.6%) for MGUS; 100.0% (97.5-100.0%) for SMM; 90.2% (85.5-93.5%) for MM; 100.0% (93.2-100.0%) for WM; and 83.6% (71.7-91.1%) for AL amyloidosis. The diagnostic specificity of the assay was 76.5% (72.2-80.3%). The EXENT System identified an M-protein in more patients than serum protein electrophoresis (SPE): 665 (92.6%) vs 611 (85.1%). The positivity rate was 90.5% vs 88.1% in MGUS; 100% vs 92.8% in SMM; 90.2% vs 80.5% in MM; 100% vs 100% in WM; and 83.6% vs 54.5% in AL amyloidosis. Conclusion The EXENT System demonstrated the same or superior diagnostic sensitivity compared to SPE. 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引用次数: 0

摘要

EXENT分析仪（The Binding Site， Thermo Fisher Scientific的一部分）的免疫球蛋白同型（GAM）检测提供了m蛋白的敏感检测、同型和定量。我们的目的是评估EXENT系统（EXENT分析仪和免疫球蛋白同型（GAM）测定EXENT分析仪）作为多发性骨髓瘤（MM）和相关疾病诊断辅助的临床性能。方法纳入1135例患者：单克隆γ病718例(MM 215例，闷烧型MM （SMM) 152例，意义不明的单克隆γ病（MGUS） 243例，Waldenström巨球蛋白血症（WM） 53例，AL淀粉样变性55例），对照417例。临床诊断根据适当的国际指南进行定义。除20例AL淀粉样变性患者外，所有单克隆γ病患者均来自美国人群。单克隆伽玛病队列的男女比例为1:1，种族多样化（白人341人，非洲裔美国人/黑人264人，亚洲43人，西班牙裔17人，未知53人）。m蛋白为IgG 359例，IgA 95例，IgM 97例，轻链89例，IgD 2例；64例患者存在1个以上m蛋白，电泳法未检出m蛋白9例。2例IgA和1例IgM患者仅鉴定出重链。在疾病对照患者中，已排除单克隆γ病的诊断。在三个试验点使用EXENT系统分析血清样本。诊断敏感性和特异性是根据使用EXENT系统将结果分类为阳性或阴性来计算的。阳性结果定义为存在M蛋白，该蛋白是完整的免疫球蛋白（IgG>/=0.359 g/L; IgA>/=0.325 g/L; IgM>/=0.227 g/L）或仅为轻链。这些同型特异性的临界值来自364名明显健康的美国受试者，使用IgG的第95百分位限值和IgA和IgM的第99百分位限值来建立IgG、IgA和IgM m蛋白的样本。阴性结果由EXENT系统定义为无m蛋白；或者如果存在完整的免疫球蛋白m蛋白，则浓度低于相应的同型特异性截止值。分别计算每种诊断（MGUS、SMM、MM、WM和AL淀粉样变性）的诊断敏感性和特异性（95%置信区间（CI）），并根据汇总结果计算。结果单克隆伽玛病的总体诊断敏感性为92.6% （CI: 90.5 ~ 94.3%）。具体来说，MGUS的诊断敏感性为90.5% (86.2-93.6%)；SMM为100.0% (97.5-100.0%)；MM占90.2% (85.5-93.5%)；WM为100.0% (93.2-100.0%)；AL淀粉样变占83.6%（71.7 ~ 91.1%）。诊断特异性为76.5%（72.2 ~ 80.3%）。EXENT系统比血清蛋白电泳（SPE）在更多的患者中鉴定出m蛋白：665（92.6%）比611（85.1%）。MGUS阳性率为90.5%比88.1%；100% vs 92.8%；MM为90.2% vs 80.5%；100% vs 100% WM；AL淀粉样变83.6% vs 54.5%。结论与SPE相比，EXENT系统具有相同或更高的诊断灵敏度。虽然该检测不被推荐作为一线筛查试验，但这种临床表现表明，它有可能成为单克隆伽玛病检查中诊断算法的一部分。

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B-350 Diagnostic performance of the EXENT® System in monoclonal gammopathy

Background The Immunoglobulin Isotypes (GAM) Assay for the EXENT Analyser (The Binding Site, part of Thermo Fisher Scientific) offers sensitive detection, isotyping and quantification of M-proteins. We aimed to assess the clinical performance of the EXENT System (The EXENT Analyser and the Immunoglobulin Isotypes (GAM) Assay for the EXENT Analyser) as an aid in diagnosis of multiple myeloma (MM) and associated disorders. Methods The study included 1135 patients: 718 with monoclonal gammopathy (215 MM, 152 smoldering MM (SMM), 243 monoclonal gammopathy of undetermined significance (MGUS), 53 Waldenström’s Macroglobulinemia (WM), and 55 AL amyloidosis), and 417 disease controls. Clinical diagnoses were defined per appropriate international guidelines. Except for 20 AL amyloidosis patients, all monoclonal gammopathy patients were from the US population. The monoclonal gammopathy cohort had a 1:1 male/female ratio and was ethnically diverse (341 White; 264 African American/ Black; 43 Asian; 17 Hispanic; 53 unknown). The M-protein was IgG in 359 patients, IgA in 95, IgM in 97, light chain-only in 89, IgD in 2; 64 patients had more than one M-protein, and no M-protein was reported by electrophoretic methods in 9 cases. Two IgA, and one IgM patient had heavy chain identified only. In the disease control patients, the diagnosis of monoclonal gammopathy had been ruled out. Serum samples were analyzed at three testing sites using the EXENT System. Diagnostic sensitivity and specificity were calculated based on categorizing results as positive or negative with the EXENT System. A positive result was defined as the presence of an M protein which was either an intact immunoglobulin (IgG>/=0.359 g/L; IgA>/=0.325 g/L; IgM>/=0.227 g/L) or a light chain-only. These isotype-specific cut-off values were established on samples from 364 apparently healthy US subjects for IgG, IgA and IgM M-proteins using the 95th percentile limit for IgG, and the 99th percentile limit for IgA and IgM. A negative result was defined as no M-protein by the EXENT System; or if intact immunoglobulin M-proteins were present, the concentration was below the corresponding isotype-specific cut-off. Diagnostic sensitivity and specificity with 95% confidence interval (CI) were calculated for each diagnosis (MGUS, SMM, MM, WM and AL amyloidosis) separately, and on the pooled results. Results The overall diagnostic sensitivity for monoclonal gammopathies was 92.6% (CI: 90.5-94.3%). Specifically, diagnostic sensitivity was 90.5% (86.2-93.6%) for MGUS; 100.0% (97.5-100.0%) for SMM; 90.2% (85.5-93.5%) for MM; 100.0% (93.2-100.0%) for WM; and 83.6% (71.7-91.1%) for AL amyloidosis. The diagnostic specificity of the assay was 76.5% (72.2-80.3%). The EXENT System identified an M-protein in more patients than serum protein electrophoresis (SPE): 665 (92.6%) vs 611 (85.1%). The positivity rate was 90.5% vs 88.1% in MGUS; 100% vs 92.8% in SMM; 90.2% vs 80.5% in MM; 100% vs 100% in WM; and 83.6% vs 54.5% in AL amyloidosis. Conclusion The EXENT System demonstrated the same or superior diagnostic sensitivity compared to SPE. Whilst the assay is not recommended as a first-line screening test, this clinical performance suggests that it has the potential to become part of the diagnostic algorithm in the workup for monoclonal gammopathies.

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来源期刊

Clinical chemistry 医学-医学实验技术

CiteScore

11.30

自引率

4.30%

发文量

212

审稿时长

1.7 months

期刊介绍： Clinical Chemistry is a peer-reviewed scientific journal that is the premier publication for the science and practice of clinical laboratory medicine. It was established in 1955 and is associated with the Association for Diagnostics & Laboratory Medicine (ADLM). The journal focuses on laboratory diagnosis and management of patients, and has expanded to include other clinical laboratory disciplines such as genomics, hematology, microbiology, and toxicology. It also publishes articles relevant to clinical specialties including cardiology, endocrinology, gastroenterology, genetics, immunology, infectious diseases, maternal-fetal medicine, neurology, nutrition, oncology, and pediatrics. In addition to original research, editorials, and reviews, Clinical Chemistry features recurring sections such as clinical case studies, perspectives, podcasts, and Q&A articles. It has the highest impact factor among journals of clinical chemistry, laboratory medicine, pathology, analytical chemistry, transfusion medicine, and clinical microbiology. The journal is indexed in databases such as MEDLINE and Web of Science.