Rupesh Raina1,2, Sidharth K Sethi3, Marie-Agnès Dragon-Durey4, Amrit Khooblall5,6, Divya Sharma7, Priyanka Khandelwal8, Ron Shapiro9, Olivia Boyer10,11, Hui Kim Yap12,13, Arvind Bagga8, Christoph Licht14,15,16. 1. Akron Nephrology Associates/Cleveland Clinic Akron General Medical Center, Akron, OH, USA. rraina@akronchildrens.org. 2. Department of Nephrology, Akron Children's Hospital, Akron, OH, USA. rraina@akronchildrens.org. 3. Kidney and Renal Transplant Institute, Medanta, The Medicity Hospital, Gurgaon, Haryana, India. 4. Hôpital Européen Georges Pompidou, APHP, INSERM UMRS1138, Université de Paris, Paris, France. 5. Akron Nephrology Associates/Cleveland Clinic Akron General Medical Center, Akron, OH, USA. 6. Department of Nephrology, Akron Children's Hospital, Akron, OH, USA. 7. Department of Medicine, Northeast Ohio Medical University, Rootstown, OH, USA. 8. Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India. 9. The Mount Sinai Hospital, New York, NY, USA. 10. Service de Néphrologie Pédiatrique, AP-HP, Centre de Référence de maladies rénales rares de l'enfant et de l'adulte (MARHEA), Hôpital Necker - Enfants Malades, 149 Rue de Sèvres, 75015, Paris, France. 11. Institut Imagine, Laboratoire des maladies rénales héréditaires, INSERM UMR 1163, Université de Paris, Paris, France. 12. Shaw-NKF-NUH Children's Kidney Centre, Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, Kent Ridge, Singapore. 13. Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. 14. Cell Biology Program, SickKids Research Institute, Toronto, ON, Canada. 15. Department of Paediatrics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada. 16. Division of Nephrology, The Hospital for Sick Children, Toronto, ON, Canada.
Abstract
BACKGROUND AND OBJECTIVES: Observing biomarkers that affect alternative pathway dysregulation components may be effective in obtaining a new and more rapid diagnostic portrayal of atypical hemolytic uremic syndrome. We have conducted a systematic review on the aHUS biomarkers: C3, C5a, C5b-9, factor B, complement factor B, H, and I, CH50, AH50, D-dimer, as well as anti-CFH antibodies. METHODS: An exhaustive literature search was conducted for aHUS patient population plasma/serum, collected/reported at the onset of diagnosis. A total of 60 studies were included with the data on 837 aHUS subjects, with at least one biomarker reported. RESULTS: The biomarkers C3 [mean (SD): 72.1 (35.0), median: 70.5 vs. reference range: 75-175 mg/dl, n = 752]; CH50 [28.3 (32.1), 24.3 vs. 30-75 U/ml, n = 63]; AH50 [27.6% (30.2%), 10% vs. ≥ 46%, n = 23]; and CFB [13.1 (6.6), 12.4, vs. 15.2-42.3 mg/dl, n = 19] were lower among aHUS subjects as compared with the reference range. The biomarkers including C4 [mean (SD): 20.4 (9.5), median: 20.5 vs. reference range: 14-40 mg/dl, n = 343]; C4d [7.2 (6.5), 4.8 vs. ≤ 9.8 μg/ml, n = 108]; CFH [40.2 (132.3), 24.5 vs. 23.6-43.1 mg/dl, n = 123 subjects]; and CFI [8.05 (5.01), 6.55 mg/dl vs. 4.4-18.1 mg/dl, n = 38] were all observed to be within the reference range among aHUS subjects. The biomarkers C5a [mean (SD): 54.9 (32.9), median: 48.8 vs. reference range: 10.6-26.3 mg/dl, n = 117]; C5b-9 [466.0 (401.4), 317 (186-569.7) vs. ≤ 250 ng/ml, n = 174]; Bb [2.6 (2.1), 1.9 vs. ≤ 1.6 μg/ml, n = 77] and D-dimer [246 (65.05), 246 vs. < 2.2 ng/ml, 2, n = 2 subjects] were higher among patients with aHUS compared with the reference range. CONCLUSION: If a comprehensive complement profile were built using our data, aHUS would be identified by low levels of C3, CH50, AH50, and CFB along with increased levels of C5a, C5b-9, Bb, anti-CFH autoantibodies, and D-dimer. A higher resolution version of the Graphical abstract is available as Supplementary information.
BACKGROUND AND OBJECTIVES: Observing biomarkers that affect alternative pathway dysregulation components may be effective in obtaining a new and more rapid diagnostic portrayal of atypical hemolytic uremic syndrome. We have conducted a systematic review on the aHUS biomarkers: C3, C5a, C5b-9, factor B, complement factor B, H, and I, CH50, AH50, D-dimer, as well as anti-CFH antibodies. METHODS: An exhaustive literature search was conducted for aHUS patient population plasma/serum, collected/reported at the onset of diagnosis. A total of 60 studies were included with the data on 837 aHUS subjects, with at least one biomarker reported. RESULTS: The biomarkers C3 [mean (SD): 72.1 (35.0), median: 70.5 vs. reference range: 75-175 mg/dl, n = 752]; CH50 [28.3 (32.1), 24.3 vs. 30-75 U/ml, n = 63]; AH50 [27.6% (30.2%), 10% vs. ≥ 46%, n = 23]; and CFB [13.1 (6.6), 12.4, vs. 15.2-42.3 mg/dl, n = 19] were lower among aHUS subjects as compared with the reference range. The biomarkers including C4 [mean (SD): 20.4 (9.5), median: 20.5 vs. reference range: 14-40 mg/dl, n = 343]; C4d [7.2 (6.5), 4.8 vs. ≤ 9.8 μg/ml, n = 108]; CFH [40.2 (132.3), 24.5 vs. 23.6-43.1 mg/dl, n = 123 subjects]; and CFI [8.05 (5.01), 6.55 mg/dl vs. 4.4-18.1 mg/dl, n = 38] were all observed to be within the reference range among aHUS subjects. The biomarkers C5a [mean (SD): 54.9 (32.9), median: 48.8 vs. reference range: 10.6-26.3 mg/dl, n = 117]; C5b-9 [466.0 (401.4), 317 (186-569.7) vs. ≤ 250 ng/ml, n = 174]; Bb [2.6 (2.1), 1.9 vs. ≤ 1.6 μg/ml, n = 77] and D-dimer [246 (65.05), 246 vs. < 2.2 ng/ml, 2, n = 2 subjects] were higher among patients with aHUS compared with the reference range. CONCLUSION: If a comprehensive complement profile were built using our data, aHUS would be identified by low levels of C3, CH50, AH50, and CFB along with increased levels of C5a, C5b-9, Bb, anti-CFH autoantibodies, and D-dimer. A higher resolution version of the Graphical abstract is available as Supplementary information.
Authors: Marina Noris; Jessica Caprioli; Elena Bresin; Chiara Mossali; Gaia Pianetti; Sara Gamba; Erica Daina; Chiara Fenili; Federica Castelletti; Annalisa Sorosina; Rossella Piras; Roberta Donadelli; Ramona Maranta; Irene van der Meer; Edward M Conway; Peter F Zipfel; Timothy H Goodship; Giuseppe Remuzzi Journal: Clin J Am Soc Nephrol Date: 2010-07-01 Impact factor: 8.237
Authors: Anna Richards; M Kathryn Liszewski; David Kavanagh; Celia J Fang; Elizabeth Moulton; Veronique Fremeaux-Bacchi; Giuseppe Remuzzi; Marina Noris; Timothy H J Goodship; John P Atkinson Journal: Mol Immunol Date: 2006-08-01 Impact factor: 4.407