Gamma Gap: A Point-of-Care Test That Correlates With Disease Burden and Treatment Response in Multiple Myeloma

Dupuis, Megan; Paul, Barry; Loitsch, Gavin; Mathews, Parker; Feinberg, Daniel; Li, Zhiguo; Tuchman, Sascha A.; Kang, Yubin

doi:10.1200/jop.19.00517

Cited by 3 publications

(1 citation statement)

References 11 publications

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“…Clinically, an arbitrary value of 4.0 g/dL is sometimes considered an elevated gamma gap even though there are no studies demonstrating an association between an elevated gamma gap and various clinical conditions [4,11]. Nevertheless, an elevated gamma gap of 4.0 g/dL may trigger further work-up such as serum electrophoresis and free light chain assessment despite a lack of published evidence informing this testing [11][12][13][14][15]. Similarly, Western blots for HIV or serologic antigen and antibody testing for HCV may be performed in response to an elevated gamma gap.…”

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confidence: 99%

Gamma gap thresholds and HIV, hepatitis C, and monoclonal gammopathy

et al. 2020

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Background An elevated gamma gap (>4 g/dL), the difference between serum total protein and albumin, can trigger testing for chronic infections or monoclonal gammopathy, despite a lack of evidence supporting this clinical threshold. Methods Using the National Health and Nutrition Examination Survey (NHANES) 1999-2014, gamma gap was derived in three subpopulations based on availability of testing for human immunodeficiency virus (HIV; N = 25,680), hepatitis C (HCV; N = 45,134), and monoclonal gammopathy of unknown significance (MGUS; N = 6,118). Disease status was confirmed by HIV antibody and Western blot, HCV RNA test, or electrophoresis with immunofixation. Sensitivity, specificity, and likelihood ratios were calculated for different gamma gap thresholds. Area under the curve (AUC) was used to assess performance and cubic splines were used to characterize the relationship between the gamma gap and each disease. Results Mean gamma gaps of participants with HIV, HCV, or MGUS ranged from 3.4-3.8 g/dL. The AUC was 0.80 (95%CI: 0.75,0.85) for HIV, 0.74 (0.72,0.76) for HCV, and 0.64 (0.60,0.69) for MGUS. An elevated gamma gap of over 4 g/dL corresponded to sensitivities of 39.3%, 19.0%, and 15.4% and specificities of 98.4%, 97.8%, and 95.4% for HIV, HCV, and MGUS, respectively. A higher prevalence of all three diseases was observed at both low and high gamma gaps.

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Section: Introductionmentioning

confidence: 99%

Gamma gap thresholds and HIV, hepatitis C, and monoclonal gammopathy

et al. 2020

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Machine Learning Approach for Rapid, Accurate Point-of-Care Prediction of M-Spike Values in Multiple Myeloma

Malek,

Wang,

Tatsuoka

et al. 2023

JCO Clinical Cancer Informatics

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Evaluation of the protein gap for detection of abnormal serum gammaglobulin level: an imperfect predictor

Suleman

Cameron

Corrales–Medina

et al. 2020

Clinical Chemistry and Laboratory Medicine (CCLM)

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ObjectivesThe value of the serum protein gap (PG, difference between total protein and albumin) in the detection of hyper- or hypogammaglobulinemia is not well established. We assessed the performance of PG for the detection of hyper- or hypogammaglobulinemia in a large sample of patients.MethodsWe reviewed all paired measurements of serum total protein, albumin, quantitative immunoglobulins, and serum protein electrophoresis tested between March 2014 and June 2017 at the Eastern Ontario Regional Laboratory Association. Sensitivity, specificity, positive predictive value, negative predictive value and likelihood ratios of PG at thresholds between 18 and 44 g/L for the detection of hyper- and hypogammaglobulinemia were assessed.ResultsThere were 19,575 and 5,426 simultaneous paired data points to assess hyper- and hypogammaglobulinemia identified by serum protein electrophoresis (SPE) and nephelometry, respectively. The mean PG was 36.3 g/L (SD 8.6). The prevalence of hypergammaglobulinemia (>16 g/L by SPE) and hypogammaglobulinemia (IgG <7 g/L) was 21.9 and 5.5%, respectively. High PG (≥38 g/L) had sensitivity and specificity of 76.2 and 71.5% respectively for hypergammaglobulinemia. PG ≥38 g/L had a negative predictive value (NPV) of 93.1% for monoclonal, and 96.9% for polyclonal gammopathy. A PG threshold of ≤18 g/L had of sensitivity of 0.4%, specificity of 100%, PPV of 100% and NPV of 80.1% to detect hypogammaglobulinemia (IgG <7 g/L).ConclusionsHigh and low PG values were not sensitive in detecting hyper- or hypogammaglobulinemia, although negative predictive values were high for both. Performance of PG should be further evaluated prospectively in specific populations at risk of for abnormal IgG levels.

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Gamma Gap: A Point-of-Care Test That Correlates With Disease Burden and Treatment Response in Multiple Myeloma

Cited by 3 publications

References 11 publications

Gamma gap thresholds and HIV, hepatitis C, and monoclonal gammopathy

Gamma gap thresholds and HIV, hepatitis C, and monoclonal gammopathy

Machine Learning Approach for Rapid, Accurate Point-of-Care Prediction of M-Spike Values in Multiple Myeloma

Evaluation of the protein gap for detection of abnormal serum gammaglobulin level: an imperfect predictor

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