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

Autoři: Gigi Y. Liu aff001;  Olive Tang aff002;  Daniel J. Brotman aff001;  Edgar R. Miller, III aff001;  Alison R. Moliterno aff003;  Stephen P. Juraschek aff001
Působiště autorů: Division of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America aff001;  The Johns Hopkins Bloomberg School of Public Health Department of Epidemiology, and The Welch Center for Prevention, Epidemiology and Clinical Research, Baltimore, Maryland, United States of America aff002;  Division of Hematology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America aff003;  Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America aff004
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224977



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.


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.


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.


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.

Klíčová slova:

Albumins – Aminotransferases – Enzyme-linked immunoassays – Hepatitis C – Hepatitis C virus – HIV – HIV diagnosis and management – Serum proteins


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