AB1247 ELEVATED SERUM COMPLEMENT (C3/C4) LEVEL AS AN INFLAMMATORY MARKER FOR INFECTION IN PATIENTS WITH FEVER: A RETROSPECTIVE STUDY
Authors: Z. Y. Li, J. Saleh, S. Huang, M. Elhassan, C. Yuvienco
Journal: Annals of the Rheumatic Diseases (2020)

Background: The functions of the complement system are to protect the host against infection, clearance of immune complexes, and regulate adaptive immunity after activation by C-reactive protein (CRP) or foreign cells. 1 C3 and C4 may increase up to 50 percent of baseline values as part of the acute-phase response, which is an expected host response for infection and injury. 2 Objectives: We aimed to examine the correlation between elevated C3/C4 levels and the underlying causes (infectious vs. non-infectious) of fever (subjective and/or objective) in adults admitted to Community Regional Medical Center (CRMC). Methods: This is a retrospective study of C3/C4 level that was ordered in adult patients who were admitted to CRMC in April 1 st , 2018 to September 30 th , 2018 with fever. This was also analyzed in comparison to elevated lactic acid, erythrocyte sedimentation rate (ESR), and CRP level. Results: Complement levels were ordered in 210 patients admitted to CRMC medicine or intensive care units. Among these patients, 28.09% (59/210) were diagnosed with various infectious diseases confirmed by gold standard methods (cultures, serology tests, computerized tomography, or magnetic resonance imaging), regardless of fever status during admission. About 26.6% (56/210) had subjective or objective (temperature greater than100.4 F or above), and 52 of them had complement levels (C3/C4) ordered with resulted in either normal or elevated. Within these 52 patients, lactic acid, ESR, and CRP were ordered in 33 , 28 , 25 of them respectively. Table 1. Elevated C3/C4 level vs. normal C3/C4 level in detecting infection in fever patients when tested against gold standards. Patients with infectious disease diagnosis Patients without infectious disease diagnosis Elevated C3 or C4 or both (screen test +) 13 7 Positive predictive value (PPV) =13/20=65% Both normal C3 and C4 (screen test -) 8 24 Negative predictive value (NPV) =15/32=48.9% Sensitivity=13/21=61.9% Specificity=24/31=77.4% Table 2. Sensitivity, specificity, PPV, NPV, likelihood ratio positive (LR+), and likelihood ratio negative (LR-) among C3/C4, lactic acid, ESR, CRPI/CRPH in detecting infection in patient with fever C3/C4 (N=52) Lactic Acid (N=33) ESR (N=28) CRPI/CRPH (N=25) Sensitivity 61.9% 50% 90% 100% Specificity 77.4% 91.3% 11.1% 11.8% PPV 65% 71.4% 36% 34.8% NPV 48.9% 80.8% 66.6% 100% LR+ 2.7 5.7 1.0 1.1 LR - 0.49 0.55 0.9 0 Conclusion: Complement levels can be used as a rapid screening test to guide infection consideration as it correctly identified 61.9 % of febrile patients with infection, and 77.4% who didn’t have an infection. A positive screening test in itself still requires further investigation in the causes of fever to confirm the diagnosis since the PPV is 65%. With the NPV of 48.9%, a negative screening test is still not reassuring that the febrile patient doesn’t have an infection. Our study demonstrated the potential utilization of the elevated complement level as an inflammatory marker for infectious etiology of fever, as it has better LR+ when compares to ESR and CRP with similar turnaround time. This study helps educate providers to acknowledge the fact that complement level does not have to be limited to be used on autoimmune related disorders only. Further large pool studies will be necessary to further investigate the role of complement levels as part of the screening test in a patient with fever. References: [1]Walport. MJ. Complement. Second of two parts. N Engl J Med.2001 Apr 12; 344(15):1140-4. DOI: 10.1056/NEJM200104123441506 [2]Wen L, Atkinson JP, Giclas PC. Clinical and laboratory evaluation of complement deficiency. J Allergy Clin Immunol. 2004;113(4):585. DOI: 10.1016/j.jaci.2004.02.003 Characters from table content: 731 Disclosure of Interests: None declared