Evaluation of the protein gap for detection of abnormal serum gammaglobulin level: an imperfect predictor.
hypergammaglobulinemia
hypogammaglobulinemia
immunoglobulin
protein electrophoresis
protein gap
Journal
Clinical chemistry and laboratory medicine
ISSN: 1437-4331
Titre abrégé: Clin Chem Lab Med
Pays: Germany
ID NLM: 9806306
Informations de publication
Date de publication:
27 04 2021
27 04 2021
Historique:
received:
23
08
2020
accepted:
29
10
2020
pubmed:
9
2
2021
medline:
10
2
2022
entrez:
8
2
2021
Statut:
epublish
Résumé
The 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. We 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. There 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). High 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.
Identifiants
pubmed: 33554546
doi: 10.1515/cclm-2020-1286
pii: cclm-2020-1286
doi:
Substances chimiques
Albumins
0
Immunoglobulin G
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
869-874Informations de copyright
© 2020 Walter de Gruyter GmbH, Berlin/Boston.
Références
Jolles, S, Borrell, R, Zouwail, S, Heaps, A, Sharp, H, Moody, M, et al.. Calculated globulin (CG) as a screening test for antibody deficiency. Clin Exp Immunol 2014;177:671–8. https://doi.org/10.1111/cei.12369.
Stohl, W, Kenol, B, Kelly, AJ, Correa, AA, Panush, RS. Elevated serum globulin gap as a highly reliable marker of elevated erythrocyte sedimentation rate in patients with systemic rheumatic diseases. Semin Arthritis Rheum 2019;49:485–92. https://doi.org/10.1016/j.semarthrit.2019.05.001.
Doweiko, JP, Nompleggi, DJ. Reviews: role of albumin in human physiology and pathophysiology. J Parenter Enteral Nutr 1991;15:207–11. https://doi.org/10.1177/0148607191015002207.
Vavricka, SR, Burri, E, Beglinger, C, Degen, L, Manz, M. Serum protein electrophoresis: an underused but very useful test. Digestion 2009;79:203–10. https://doi.org/10.1159/000212077.
Dupuis, MM, Paul, B, Loitsch, G, Mathews, P, Feinberg, D, Barak, I, et al.. Gamma gap: a point-of-care test that correlates with disease burden and treatment response in multiple myeloma. JCO Oncol Pract 2020;16:e751–7. https://doi.org/10.1200/JOP.19.00517.
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;23:1688–92. https://doi.org/10.1007/s11606-008-0712-z.
Holding, S, Khan, S, Sewell, WAC, Jolles, S, Dore, PC. Using calculated globulin fraction to reduce diagnostic delay in primary and secondary hypogammaglobulinaemias: results of a demonstration project. Ann Clin Biochem 2015;52:319–26. https://doi.org/10.1177/0004563214545791.
Pecoraro, A, Jolles, S, Crescenzi, L, Varricchi, G, Marone, G, Savoia, M, et al.. Validation of calculated globulin (CG) as a screening test for antibody deficiency in an Italian University Hospital [Internet]. Curr Pharmaceut Biotechnol 2018;19:728–33. Available from: https://www.eurekaselect.com/164507/article [Cited 19 Jul 2020].
Phelps, MA, Levitt, MA. Pretest probability estimates: a pitfall to the clinical utility of evidence‐based medicine? Acad Emerg Med 2004;11:692–4. https://doi.org/10.1197/j.aem.2003.08.022.
IBM Corp. IBM SPSS statistics for Windows, version 24.0. Armonk, NY: IBM Corp.; 2016.
Rajkumar, SV, Dimopoulos, MA, Palumbo, A, Blade, J, Merlini, G, Mateos, MV, et al.. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 2014;15:e538–48. https://doi.org/10.1016/s1470-2045(14)70442-5.
Dispenzieri, A, Gertz, MA, Therneau, TM, Kyle, RA. Retrospective cohort study of 148 patients with polyclonal gammopathy. Mayo Clin Proc 2001;76:476–87. https://doi.org/10.4065/76.5.476.
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. https://doi.org/10.1038/s41598-018-19534-4.
Tannou, T, Koeberle, S, Manckoundia, P, Aubry, R. Multifactorial immunodeficiency in frail elderly patients: contributing factors and management. Médecine Mal Infect 2019;49:167–72. https://doi.org/10.1016/j.medmal.2019.01.012.
Cowan, J, Do, TL, Desjardins, S, Ramotar, K, Corrales-Medina, V, Cameron, DW. Prevalence of hypogammaglobulinemia in adult invasive pneumococcal disease. Clin Infect Dis 2018;66:564–9. https://doi.org/10.1093/cid/cix836.
Wadhera, RK, Rajkumar, SV. Prevalence of monoclonal gammopathy of undetermined significance: a systematic review. Mayo Clin Proc 2010;85:933–42. https://doi.org/10.4065/mcp.2010.0337.