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Diagnosis of complement alternative pathway disorders
Journal article   Open access   Peer reviewed

Diagnosis of complement alternative pathway disorders

Andrea Angioi, Fernando C Fervenza, Sanjeev Sethi, Yuzhou Zhang, Richard J Smith, David Murray, Jens Van Praet, Antonello Pani and An S De Vriese
Kidney international, Vol.89(2), pp.278-288
02/2016
DOI: 10.1016/j.kint.2015.12.003
PMID: 26806831
url
https://doi.org/10.1016/j.kint.2015.12.003View
Published (Version of record) Open Access

Abstract

Kidney diseases resulting from abnormal control of the complement alternative pathway include atypical hemolytic uremic syndrome, C3 glomerulonephritis, and dense-deposit disease, as well as atypical postinfectious glomerulonephritis. Although clinically diverse, they all result from loss of surface or fluid-phase complement control, caused by acquired or genetic defects in the complement alternative pathway. As such, the diagnostic approach is similar and includes a comprehensive biochemical, genetic, and pathologic analysis of the complement pathway. The biochemical test battery includes functional activity measurements of the entire complement pathway, functional and quantitative analysis of individual components and regulators, and quantification of activation products. In patients with a thrombotic microangiopathy, ADAMTS-13 activity should be determined to exclude a thrombotic thrombocytopenic purpura. The spectrum of genes currently known to be involved in the pathogenesis of alternative pathway disorders is rapidly expanding. Pathologic analysis of a kidney biopsy specimen is sophisticated with ad hoc immunofluorescence studies and laser microdissection with mass spectrometry. The identification of the underlying defect in the alternative pathway based on this comprehensive analysis will allow treatment to be directed to the site of dysregulation.
atypical hemolytic uremic syndrome alternative pathway classical pathway C3 glomerulopathy complement glomerulonephritis C3 glomerulonephritis dense-deposit disease

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