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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: https://doi.org/10.1371/journal.pone.0224977

Souhrn

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.

Klíčová slova:

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


Zdroje

1. Feldman LS, Shihab HM, Thiemann D, Yeh H-C, Ardolino M, Mandell S, et al. Impact of providing fee data on laboratory test ordering: a controlled clinical trial. JAMA Intern Med. 2013;173: 903–908. doi: 10.1001/jamainternmed.2013.232 23588900

2. Vavricka SR, Burri E, Beglinger C, Degen L, Manz M. Serum protein electrophoresis: an underused but very useful test. Digestion. 2009;79: 203–210. doi: 10.1159/000212077 19365122

3. Thakkinstian A, Tran H, Reeves G, Murch S, Attia J. A clinical decision rule to aid ordering of serum and urine protein electrophoresis for case-finding of paraproteins in hospitalized inpatients. J Gen Intern Med. 2008;23: 1688–1692. doi: 10.1007/s11606-008-0712-z 18665429

4. Juraschek SP, Moliterno AR, Checkley W, Miller ER. The Gamma Gap and All-Cause Mortality. PLoS ONE. 2015;10: e0143494. doi: 10.1371/journal.pone.0143494 26629820

5. Salt HB. Serum globulin fractions in chronic rheumatic diseases; an electrophoretic study. Clin Chem. 1956;2: 35–44. 13284964

6. Suh B, Park S, Shin DW, Yun JM, Keam B, Yang H-K, et al. Low albumin-to-globulin ratio associated with cancer incidence and mortality in generally healthy adults. Ann Oncol. 2014;25: 2260–2266. doi: 10.1093/annonc/mdu274 25057172

7. Dispenzieri A, Gertz MA, Therneau TM, Kyle RA. Retrospective cohort study of 148 patients with polyclonal gammopathy. Mayo Clin Proc. 2001;76: 476–487. doi: 10.4065/76.5.476 11357794

8. O’Connell TX, Horita TJ, Kasravi B. Understanding and interpreting serum protein electrophoresis. Am Fam Physician. 2005;71: 105–112. 15663032

9. Yang M, Xie L, Liu X, Hao Q, Jiang J, Dong B. The gamma gap predicts 4-year all-cause mortality among nonagenarians and centenarians. Sci Rep. 2018;8: 1046. doi: 10.1038/s41598-018-19534-4 29348636

10. Loprinzi PD, Addoh O. The gamma gap and all-cause mortality risk: considerations of physical activity. Int J Clin Pract. 2016;70: 625–629. doi: 10.1111/ijcp.12817 27292974

11. Pirrucello J. Gamma Gap [Internet]. [cited 8 Mar 2019]. Available: http://james.pirruccello.us/index.php?title=Gamma_gap

12. Clarke K, Dobro S, Brandes L. Always Work Up a Significant Globulin Gap [Abstract]. Hospital Medicine. Available: https://www.shmabstracts.com/abstract/always-work-up-a-significant-globulin-gap/

13. Stohl W, Kenol B, Kelly A, Ananth Correa A, Panush R. Elevated Serum Globulin Gap As a Reliable and Cost-Savings Marker of Inflammation in Patients with Systemic Rheumatic Diseases [Abstract]. Arthritis Rheum. 2018;70. Available: https://acrabstracts.org/abstract/elevated-serum-globulin-gap-as-a-reliable-and-cost-savings-marker-of-inflammation-in-patients-with-systemic-rheumatic-diseases/

14. Wheeler D. VA Report: The Elevated Protein Gap. 2016; Available: https://ucsfmed.wordpress.com/2016/02/29/va-report-the-elevated-protein-gap/

15. Dupuis M, Zhiguo Li Z, Tuchman S, Kang Y. The Gamma Gap: A Point-of-Care Test That Correlates with Disease Burden and Treatment Response in Multiple Myeloma. Blood. 2017;130: 4407.

16. Hughes M, Davidson DF, McColl M. Outcomes of discretionary laboratory requesting of serum protein electrophoresis. Ann Clin Biochem. 2006;43: 372–374. doi: 10.1258/000456306778520133 17022879

17. Malacrida V, De Francesco D, Banfi G, Porta FA, Riches PG. Laboratory investigation of monoclonal gammopathy during 10 years of screening in a general hospital. J Clin Pathol. 1987;40: 793–797. doi: 10.1136/jcp.40.7.793 3114329

18. NHANES 1999–2014: Standard Biochemistry Profile & Hormones Data Documentation, Codebook, and Frequencies [Internet]. Available: wwwn.cdc.gov/Nchs/Nhanes

19. NHANES 1999–2014: HIV Antibody Test, CD4+ T Lymphocytes & CD8+ T Cells Data Documentation, Codebook, and Frequencies [Internet]. Available: wwwn.cdc.gov/Nchs/Nhanes

20. NHANES 1999–2004: Hepatitis B: Core Antibody & Surface Antigen; Hepatitis C: Confirmed Antibody & RNA (HCV-RNA); Hepatitis D Antibody Data Documentation, Codebook, and Frequencies [Internet]. Available: wwwn.cdc.gov/Nchs/Nhanes/

21. NHANES 2005–2014: Hepatitis C: Confirmed Antibody, RNA (HCV-RNA), & Genotype Data Documentation, Codebook, and Frequencies [Internet]. Available: https://wwwn.cdc.gov/Nchs/Nhanes

22. NHANES 1999–2004: Monoclonal gammopathy of undetermined significance (MGUS) (Surplus) Data Documentation, Codebook, and Frequencies [Internet]. Available: wwwn.cdc.gov/Nchs/Nhanes

23. Shirai A, Cosentino M, Leitman-Klinman SF, Klinman DM. Human immunodeficiency virus infection induces both polyclonal and virus-specific B cell activation. J Clin Invest. 1992;89: 561–566. doi: 10.1172/JCI115621 1737846

24. De Milito A, Nilsson A, Titanji K, Thorstensson R, Reizenstein E, Narita M, et al. Mechanisms of hypergammaglobulinemia and impaired antigen-specific humoral immunity in HIV-1 infection. Blood. 2004;103: 2180–2186. doi: 10.1182/blood-2003-07-2375 14604962

25. Serpa J, Haque D, Valayam J, Breaux K, Rodriguez-Barradas MC. Effect of combination antiretroviral treatment on total protein and calculated globulin levels among HIV-infected patients. Int J Infect Dis. 2010;14 Suppl 3: e41–44. doi: 10.1016/j.ijid.2009.10.007 20137993

26. Scherzer R, Heymsfield SB, Rimland D, Powderly WG, Tien PC, Bacchetti P, et al. Association of serum albumin and aspartate transaminase with 5-year all-cause mortality in HIV/hepatitis C virus coinfection and HIV monoinfection. AIDS. 2017;31: 71–79. doi: 10.1097/QAD.0000000000001278 27677166

27. Adedeji AL, Adenikinju RO, Ajele JO, Olawoye TL. Serum protein electrophoresis under effective control of HIV-1 disease progression. EXCLI J. 2014;13: 761–771. 26417299

28. Konstantinopoulos PA, Dezube BJ, Pantanowitz L, Horowitz GL, Beckwith BA. Protein electrophoresis and immunoglobulin analysis in HIV-infected patients. Am J Clin Pathol. 2007;128: 596–603. doi: 10.1309/QWTQFGA9FXN02YME 17875511

29. Redgrave BE, Stone SF, French M a. H, Krueger R, James IR, Price P. The effect of combination antiretroviral therapy on CD5 B-cells, B-cell activation and hypergammaglobulinaemia in HIV-1-infected patients. HIV Med. 2005;6: 307–312. doi: 10.1111/j.1468-1293.2005.00312.x 16156877

30. Sugalski JM, Rodriguez B, Moir S, Anthony DD. Peripheral blood B cell subset skewing is associated with altered cell cycling and intrinsic resistance to apoptosis and reflects a state of immune activation in chronic hepatitis C virus infection. J Immunol. 2010;185: 3019–3027. doi: 10.4049/jimmunol.1000879 20656924

31. Cornella SL, Stine JG, Kelly V, Caldwell SH, Shah NL. Persistence of mixed cryoglobulinemia despite cure of hepatitis C with new oral antiviral therapy including direct-acting antiviral sofosbuvir: A case series. Postgrad Med. 2015;127: 413–417. doi: 10.1080/00325481.2015.1021660 25746436

32. Gonzàlez-Quintela A, Alende MR, Gamallo R, Gonzàlez-Gil P, López-Ben S, Tomé S, et al. Serum immunoglobulins (IgG, IgA, IgM) in chronic hepatitis C. A comparison with non-cirrhotic alcoholic liver disease. Hepatogastroenterology. 2003;50: 2121–2126. 14696478

33. Maruyama S, Hirayama C, Horie Y, Yorozu K, Maeda K, Inoue M, et al. Serum immunoglobulins in patients with chronic hepatitis C: a surrogate marker of disease severity and treatment outcome. Hepatogastroenterology. 2007;54: 493–498. 17523306

34. Zhang G-L, Chen Y-M, Zhang T, Cai Q-X, Zhang X-H, Zhao Z-X, et al. Favorable Outcomes of Chinese HCV-Related Cirrhotic Patients with Sustained Virological Response after Pegylated Interferon Plus Ribavirin Treatment. Biomed Res Int. 2017;2017: 8061091. doi: 10.1155/2017/8061091 28232944

35. Kádár K, Wolf K, Tábori J, Karádi I, Várkonyi J. The albumin and monoclonal protein ratio as prognostic marker for multiple myeloma in the era of novel agents. Pathol Oncol Res. 2012;18: 557–561. doi: 10.1007/s12253-012-9506-z 22314327

36. Kim JE, Yoo C, Lee DH, Kim S-W, Lee J-S, Suh C. Serum albumin level is a significant prognostic factor reflecting disease severity in symptomatic multiple myeloma. Ann Hematol. 2010;89: 391–397. doi: 10.1007/s00277-009-0841-4 19844712

37. Waxman AJ, Mick R, Garfall AL, Cohen A, Vogl DT, Stadtmauer EA, et al. Classifying ultra-high risk smoldering myeloma. Leukemia. 2015;29: 751–753. doi: 10.1038/leu.2014.313 25371175

38. Bladé J, Rosiñol L, Cibeira MT, de Larrea CF. Pathogenesis and progression of monoclonal gammopathy of undetermined significance. Leukemia. 2008;22: 1651–1657. doi: 10.1038/leu.2008.203 18668131

39. Cesana C, Klersy C, Barbarano L, Nosari AM, Crugnola M, Pungolino E, et al. Prognostic factors for malignant transformation in monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. J Clin Oncol. 2002;20: 1625–1634. doi: 10.1200/JCO.2002.20.6.1625 11896113

40. Branson BM, Handsfield HH, Lampe MA, Janssen RS, Taylor AW, Lyss SB, et al. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. MMWR Recomm Rep. 2006;55: 1–17; quiz CE1-4.

41. AASLD/IDSA HCV Guidance Panel. Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus. Hepatology. 2015;62: 932–954. doi: 10.1002/hep.27950 26111063


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