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

Gigi Y. Liu, Olive Tang, Daniel J. Brotman, Edgar R. Miller, Alison R. Moliterno, Stephen P. Juraschek

Research output: Contribution to journalArticle

Abstract

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. Discussion An elevated gamma gap of 4 g/dL is insensitive for HIV, HCV, or MGUS, but has a high specificity for HIV and HCV, suggesting that the absence of an elevated gamma gap does not rule out HIV, HCV, or MGUS. Conversely, an elevated gap may justify further testing for HIV and HCV, but does not justify electrophoresis in the absence of additional clinical information.

Original languageEnglish (US)
Article numbere0224977
JournalPloS one
Volume15
Issue number1
DOIs
StatePublished - Jan 2020

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hepatitis C
Paraproteinemias
Hepatitis C
HIV
Electrophoresis
Testing
electrophoresis
HIV Antibodies
testing
Nutrition
Viruses
Splines
National Health and Nutrition Examination Survey
Albumins
Human immunodeficiency virus
Health
Availability
RNA
blood proteins
albumins

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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Liu, G. Y., Tang, O., Brotman, D. J., Miller, E. R., Moliterno, A. R., & Juraschek, S. P. (2020). Gamma gap thresholds and HIV, hepatitis C, and monoclonal gammopathy. PloS one, 15(1), [e0224977]. https://doi.org/10.1371/journal.pone.0224977

Gamma gap thresholds and HIV, hepatitis C, and monoclonal gammopathy. / Liu, Gigi Y.; Tang, Olive; Brotman, Daniel J.; Miller, Edgar R.; Moliterno, Alison R.; Juraschek, Stephen P.

In: PloS one, Vol. 15, No. 1, e0224977, 01.2020.

Research output: Contribution to journalArticle

Liu, GY, Tang, O, Brotman, DJ, Miller, ER, Moliterno, AR & Juraschek, SP 2020, 'Gamma gap thresholds and HIV, hepatitis C, and monoclonal gammopathy', PloS one, vol. 15, no. 1, e0224977. https://doi.org/10.1371/journal.pone.0224977
Liu, Gigi Y. ; Tang, Olive ; Brotman, Daniel J. ; Miller, Edgar R. ; Moliterno, Alison R. ; Juraschek, Stephen P. / Gamma gap thresholds and HIV, hepatitis C, and monoclonal gammopathy. In: PloS one. 2020 ; Vol. 15, No. 1.
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abstract = "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. Discussion An elevated gamma gap of 4 g/dL is insensitive for HIV, HCV, or MGUS, but has a high specificity for HIV and HCV, suggesting that the absence of an elevated gamma gap does not rule out HIV, HCV, or MGUS. Conversely, an elevated gap may justify further testing for HIV and HCV, but does not justify electrophoresis in the absence of additional clinical information.",
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N2 - 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. Discussion An elevated gamma gap of 4 g/dL is insensitive for HIV, HCV, or MGUS, but has a high specificity for HIV and HCV, suggesting that the absence of an elevated gamma gap does not rule out HIV, HCV, or MGUS. Conversely, an elevated gap may justify further testing for HIV and HCV, but does not justify electrophoresis in the absence of additional clinical information.

AB - 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. Discussion An elevated gamma gap of 4 g/dL is insensitive for HIV, HCV, or MGUS, but has a high specificity for HIV and HCV, suggesting that the absence of an elevated gamma gap does not rule out HIV, HCV, or MGUS. Conversely, an elevated gap may justify further testing for HIV and HCV, but does not justify electrophoresis in the absence of additional clinical information.

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