Study of the Validity of Neutrophil CD64 and Serum Procalcitonin as Diagnostic Markers to Discriminate Infection from Disease Activity in Patients with Systemic Lupus Erythematosus
American Journal of Clinical and Experimental Medicine
Volume 3, Issue 3, May 2015, Pages: 110-117
Received: Apr. 21, 2015; Accepted: Apr. 27, 2015; Published: May 13, 2015
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Ahmed Ragheb, Internal Medicine Department, Faculty of Medicine, Menoufia University, Shebin Elkom, Menoufia, Egypt
Ahmed A. Sonbol, Clinical Pathology Department, Faculty of Medicine, Menoufia University, Shebin Elkom, Menoufia, Egypt
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Introduction: In addition to the complexity of the clinical presentation of both infections and disease activity in systemic lupus erythematosus (SLE) patients, the difficulty in making the therapeutic decision require investigations that should be of diagnostic value. Neutrophil CD64 is up regulated within few hours in patients with infection. Similarly, serum procalcitonin (PCT) levels increase rapidly following bacterial infection. Objective: The aim of this work is to study the usefulness of neutrophil CD64 expression and serum PCT as diagnostic markers to discriminate infection from disease activity in patients with systemic lupus erythematosus. Methods: This study was carried on 20 healthy females as controls (group I) and 55 female patients with SLE. Patients were distributed as following; 20 SLE patients without activity or infections (group II), 20 SLE patients with lupus activity (group III), and 15 SLE patients with infection (group IV). CBC, ANA, Anti-ds DNA, C3 and C4 were measured in all population. Serum PCT was measured by ELFA and neutrophil CD64 expression was done by flowcytometry. Results: Neutrophil CD64 expression and serum PCT levels were increased significantly in SLE patients with infection compared to those with disease activity. We demonstrated significant correlations between CD64 and markers of both activity and infection, while serum PCT levels were significantly correlated with markers of infection. The area under the ROC curves for detection of infection (AUC; 95% CI) for neutrophil CD64 expression and serum PCT were (0.90; 0.79-1.01) and (0.99; 0.95-1.01), respectively. Conclusion: Our findings can prove that both neutrophil CD64 and serum PCT are reliable markers to discriminate infection from disease activity in SLE patients. Serum PCT was more accurate than neutrophil CD64 expression.
Systemic Lupus Erythematosus, Lupus Activity, Infection, CD64, Procalcitonin
To cite this article
Ahmed Ragheb, Ahmed A. Sonbol, Study of the Validity of Neutrophil CD64 and Serum Procalcitonin as Diagnostic Markers to Discriminate Infection from Disease Activity in Patients with Systemic Lupus Erythematosus, American Journal of Clinical and Experimental Medicine. Vol. 3, No. 3, 2015, pp. 110-117. doi: 10.11648/j.ajcem.20150303.17
Marian V, Anolik JH. Treatment targets in systemic lupus erythematosus: biology and clinical perspective. Arthritis Research & Therapy 2012; 14:S3.
Davis BH. Improved diagnostic approaches to infection/sepsis detection. Expert Rev Mol Diagn 2005; 5:193-207.
Doi T, Miyazaki T, Nishino J, Tanaka S, Matsui T, Komiya A et al. Neutrophil CD64 expression as a diagnostic marker for local infection and crystal-induced arthritis. Mod Rheumatol 2010; 20(6):573-9.
Livaditi O, Kotanidou A, Psarra A, Dimopoulou I, Sotiropoulou C, Augustatou K et al. Neutrophil CD64 expression and serum IL-8: sensitive early markers of severity and outcome in sepsis. Cytokine 2006; 36:283-90.
Hoffmann J. Neutrophil CD64 as a sepsis biomarker. Biochemia Medica 2011; 21:282-90.
Assicot M, Gendrel D, Carsin H, Raymond J, Guilbaud J, Bohuon C. High serum procalcitonin concentrations in patients with sepsis and infection. Lancet 1993; 341:515-8.
Suzuki N, Mizuno H, Nezu M, Takai Y, Misu T, Kuroda H, et al. Procalcitonin might help in discrimination between meningeal neuro-Behcet disease and bacterial meningitis. Neurology 2009; 72:762-3.
Tamaki K, Kogata Y, Sugiyama D, Nakazawa T, Hatachi S, Kageyama G, et al. Diagnostic accuracy of serum procalcitonin concentrations for detecting systemic bacterial infection in patients with systemic autoimmune diseases. J Rheumatol 2008; 35:114-9.
Joo K, Park W, Lim MJ, Kwon SR, Yoon J. serum procalcitonin for differentiating bacterial infection from disease flares in patients with autoimmune diseases. J Korean Med Sci 2011; 26:1147-51.
Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25(11):1271-7.
Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40:172-5.
Gladman DD, Ibanez D, Urowitz MB. Systemic Lupus Erythematosus Disease Activity Index 2000. J Rheumatol 2002; 29:288-91.
Hussein OA, El-Toukhy MA, and El-Rahman HS. Neutrophil CD64 Expression in Inflammatory Autoimmune Diseases: Its Value in Distinguishing Infection from Disease Flare. Immunol Invest 2010; 39:699-712.
Liu S, Ren J, Xia Q, Wu X, Han G, Ren H et al. Preliminary Case-control Study to Evaluate Diagnostic Values of C-Reactive Protein and Erythrocyte Sedimentation Rate in Differentiating Active Crohn's Disease From Intestinal Lymphoma, Intestinal Tuberculosis and Behcet's Syndrome. Am j med sci 2013; 346 (6): 467–72.
Hindocha P, Campbell CA, Gould JD, Wojciechowski A, Wood CB. Sequential study of C reactive protein in neonatal septicaemia using a latex agglutination test. J Clin Pathol 1984; 37(9):1014-7.
Homburger HA, Cahen YD, Griffiths J, Jacob G. Detection of antinuclear antibodies: Comparative evaluation of enzyme immunoassay and indirect immunofluorescence methods. Arch of Pathol Lab Med 1998; 122(11): 993-9.
Stokes RP, Cordwell A and Thompson RA; A simple, rapid ELISA method for detection of DNA antibodies. J Clin Pathol 1982; 35: 566-73.
Frederikson GN, Truedsson L and Sjoeholm AG. New procedure for detection of complement deficiency by ELISA, analysis of activation pathway and circumvention of rheumatoid factor influence. J Immunol Methods 1993; 166(2): 263-70.
Brown M, Wittwer C. Flow cytometry: principles and clinical applications in hematology. Clin Chem. 2000; 46:1221-9.
Deneys V, Michaux L, Leveugle P, Mazzon AM, Gillis E, Ferrant A et al. Atypical lymphocytic leukemia and mantle cell lymphoma immunologically very close: flow cytometric distinction by the use of CD20 and CD54 expression. Leukemia 2001; 15(9):1458-65.
Schuetz P, Briel M, Christ-Crain M, Stolz D, Bouadma L, Wolff M et al. Procalcitonin to Guide Initiation and Duration of Antibiotic Treatment in Acute Respiratory Infections: An Individual Patient Data Meta-Analysis. Clin Infect Dis 2012; 55(5):651-62.
Kopterides P, Siempos, II, Tsangaris I, Tsantes A and Armaganidis A. Procalcitonin-guided algorithms of antibiotic therapy in the intensive care unit:a systematic review and metaanalysis of randomized controlled trials. Crit Care Med 2010; 38(11): 2229-41.
Goldblatt F, Chambers S, Rahman A, Isenberg DA. Serious infections in British patients with systemic lupus erythematosus: hospitalisations and mortality. Lupus 2009; 18(8):682-9.
Jalava-Karvinen P, Hohenthal U, Laitinen I, Kotilainen P, Rajamäki A, Nikoskelainen J, et al. Simultaneous quantitative analysis of Fc gamma RI (CD64) and CR1 (CD35) on neutrophils in distinguishing between bacterial infections, viral infections, and inflammatory diseases. Clin Immunol 2009; 133:314-323.
Qureshi SS, Lewis SM, Gant VA, Treacher D, Davis BH, Brown KA. Increased distribution and expression of CD64 on blood polymorphonuclear cells from patients with the systemic inflammatory response syndrome (SIRS). Clin Exp Immunol 2001; 125:258–65.
Wu JY, Lee SH, Shen CJ, Hsieh YC, Yo PH, Cheng HY, et al. Use of Serum PCT to Detect Bacterial Infection in Patients with Autoimmune Diseases. A Systemic Review and Meta-Analysis. Arthritis Rheum 2012; 64 (9): 3034–42.
Allen E, Bakke AC, Purtze MZ, Deodhar A. Neutrophil CD64 expression distinguishing acute inflammatory disease from systemic infections. Ann Rheum Dis 2002; 61(6):522-5.
Goulding NJ, Knight SM, Godolphin JL, Guyre PM. Increase in neutrophil Fc gamma receptor I expression following interferon gamma treatment in rheumatoid arthritis. Ann Rheum Dis 1992; 51(4):465-8.
Szucs G, Kavai M, Kiss E. Correlation of IgG Fc receptors on granulocytes with serum immune complex level insystemic lupus erythrematosus. Scand J Immunol 1995; 42:577-80.
Brunkhorst R, Eberhardt OK, Haubitz M, Brunkhorst FM. Procalcitonin for discrimination between activity of systemic autoimmune disease and systemic bacterial infection. Intensive Care Med 2000; 26 (2):199–201.
Chen DY, Chen YM, Ho WL, Chen HH, Shen GH, Lan JL. Diagnostic value of procalcitonin for differentiation between bacterial infection and non-infectious inflammation in febrile patients with active adult-onset Still’s disease. Ann Rheum Dis 2009; 68:1074–5.
Eberhard OK, Haubitz M, Brunkhorst FM, Kliem V, Koch KM, Brunkhorst R. Usefulness of procalcitonin for differentiation between activity of systemic autoimmune disease (systemic lupus erythematosus/systemic antineutrophil cytoplasmic antibody–associated vasculitis) and invasive bacterial infection. Arthritis Rheum 1997; 40:1250-6.
Martinot M, Sordet C, Soubrier M, Puechal X, Saraux A, Liote F, et al. Diagnostic value of serum and synovial procalcitonin in acute arthritis: a prospective study of 42 patients. Clin Exp Rheumatol 2005; 23:303-10.
Scire CA, Cavagna L, Perotti C, Bruschi E, Caporali R, Montecucco C. Diagnostic value of procalcitonin measurement in febrile patients with systemic autoimmune diseases. Clin Exp Rheumatol 2006; 24:123-8.
Cardelli P1, Ferraironi M, Amodeo R, Tabacco F, De Blasi RA, Nicoletti M, et al. Evaluation of neutrophil CD64 expression and procalcitonin as useful markers in early diagnosis of sepsis. Int J Immunopathol Pharmacol. 2008; 21(1):43-9.
Gibot S, Béné MC, Noel R, Massin F, Guy J, Cravoisy A, et al. Combination biomarkers to diagnose sepsis in the critically ill patient. Am J Respir Crit Care Med. 2012; 186 (1):65-71.
Zeitoun AA, Gad SS, Attia FM, Abu Maziad AS, Bell EF. Evaluation of neutrophilic CD64, interleukin 10 and procalcitonin as diagnostic markers of early- and late-onset neonatal sepsis. Scand J Infect Dis. 2010; 42 (4):299-305.
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