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Diagnostic Utility of Complement Serology for Atypical Hemolytic Uremic Syndrome



      To investigate the clinical utility of a 9-analyte complement serology panel (COMS) covering complement function (CH50 and AH50), components (C3, C4), factor B (CFB), factor H, and activation markers (C4d, Bb, and soluble membrane attack complex) for the diagnosis of atypical hemolytic uremic syndrome (aHUS).


      Physician orders for COMS from January 19, 2015, through November 4, 2016, were reviewed. Demographic characteristics, patient diagnosis, and laboratory parameters were recorded.


      There were 177 COMS orders for 147 patients. The median patient age was 44.9 years (range, 0.9-88.0 years). Common reasons for ordering COMS included monitoring and diagnosis of C3 glomerulopathy and renal dysfunction and differentiation of aHUS from other thrombotic microangiopathies (TMAs). Forty-four patients had COMS ordered for TMAs: 8 had aHUS and all had 1 or more abnormalities within the alternative pathway of complement. Although the sensitivity of this finding for the diagnosis of aHUS is 100%, the specificity is only 28%, with a positive likelihood ratio of 1.39. Patients with aHUS had lower CH50, C3, and CFB than did those with secondary non-aHUS TMA (all P<.01). A combined CFB of 20.9 mg/dL or less and CH50 of 56% or less led to sensitivity of 75% with increased specificity of 88.9% and a diagnostic odds ratio of 24.


      A COMS abnormality should not be interpreted in isolation. In conjunction with clinical presentation, a decrease in both CFB and CH50 may be an important clue to support the diagnosis of aHUS.

      Abbreviations and Acronyms:

      aHUS (atypical hemolytic uremic syndrome), AP (alternative pathway), C3 (complement component 3), C5 (complement component 5), C3G (C3 glomerulopathy), CFB (complement factor B), CFH (complement factor H), CFI (complement factor I), COMS (complement serology panel), ELISA (enzyme-linked immunosorbent assay), G6P (glucose-6-phosphate), HRP (horseradish peroxidase), HUS (hemolytic uremic syndrome), MAC (membrane attack complex), ROC (receiver operating characteristic), SCR (short consensus repeat), SLE (systemic lupus erythematosus), sMAC (soluble membrane attack complex), TMA (thrombotic microangiopathy), TPE (therapeutic plasma exchange), TTP (thrombotic thrombocytopenic purpura), VUS (variant of uncertain significance)
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      Linked Article

      • Complement Biomarkers of Hemolytic Uremic Syndrome—If Not One Thing, Maybe Another
        Mayo Clinic ProceedingsVol. 93Issue 10
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          Great progress has been made in our understanding of atypical hemolytic uremic syndrome (aHUS) during the past 15 years. Genetic and serologic studies have revealed that the disease is strongly associated with molecular defects causing overactivity of the complement cascade.1 Several different animal models have confirmed that these genetic defects in complement regulation are causative of disease and that complement activation is a critical driver of tissue injury.2 Based on these findings, patients with aHUS have been treated with the complement inhibitory drug eculizumab.
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