» Articles » PMID: 25862562

Modified Ham Test for Atypical Hemolytic Uremic Syndrome

Overview
Journal Blood
Publisher Elsevier
Specialty Hematology
Date 2015 Apr 12
PMID 25862562
Citations 48
Authors
Affiliations
Soon will be listed here.
Abstract

Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy (TMA) characterized by excessive activation of the alternative pathway of complement (APC). Atypical HUS is frequently a diagnosis of exclusion. Differentiating aHUS from other TMAs, especially thrombotic thrombocytopenic purpura (TTP), is difficult due to overlapping clinical manifestations. We sought to develop a novel assay to distinguish aHUS from other TMAs based on the hypothesis that paroxysmal nocturnal hemoglobinuria cells are more sensitive to APC-activated serum due to deficiency of glycosylphosphatidylinositol- anchored complement regulatory proteins (GPI-AP). Here, we demonstrate that phosphatidylinositol-specific phospholipase C-treated EA.hy926 cells and PIGA-mutant TF-1 cells are more susceptible to serum from aHUS patients than parental EA.hy926 and TF-1 cells. We next studied 31 samples from 25 patients with TMAs, including 9 with aHUS and 12 with TTP. Increased C5b-9 deposition was evident by confocal microscopy and flow cytometry on GPI-AP-deficient cells incubated with aHUS serum compared with heat-inactivated control, TTP, and normal serum. Differences in cell viability were observed in biochemically GPI-AP-deficient cells and were further increased in PIGA-deficient cells. Serum from patients with aHUS resulted in a significant increase of nonviable PIGA-deficient TF-1 cells compared with serum from healthy controls (P < .001) and other TMAs (P < .001). The cell viability assay showed high reproducibility, sensitivity, and specificity in detecting aHUS. In conclusion, we developed a simple, rapid, and serum-based assay that helps to differentiate aHUS from other TMAs.

Citing Articles

C5b-9 Deposition Test to Monitor Complement Activity in Clinical and Subclinical Atypical Hemolytic Uremic Syndrome and in Transplantation-Associated Thrombotic Microangiopathy.

Martin M, Llorens-Cebria C, Leon-Roman J, Perurena-Prieto J, Perez-Beltran V, Saumell S Kidney Int Rep. 2024; 9(7):2227-2239.

PMID: 39081726 PMC: 11284441. DOI: 10.1016/j.ekir.2024.04.022.


Increased Complement Activation and Decreased ADAMTS13 Activity Are Associated with Genetic Susceptibility in Patients with Preeclampsia/HELLP Syndrome Compared to Healthy Pregnancies: An Observational Case-Controlled Study.

Venou T, Vetsiou E, Varelas C, Daniilidis A, Psarras K, Koravou E J Pers Med. 2024; 14(4).

PMID: 38673014 PMC: 11051193. DOI: 10.3390/jpm14040387.


Can complement activation be the missing link in antiphospholipid syndrome?.

Venturelli V, Maranini B, Tohidi-Esfahani I, Isenberg D, Cohen H, Efthymiou M Rheumatology (Oxford). 2024; 63(12):3243-3254.

PMID: 38483257 PMC: 11637425. DOI: 10.1093/rheumatology/keae178.


Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR) and Growth Differentiation Factor-15 (GDF-15) Levels Are Significantly Associated with Endothelial Injury Indices in Adult Allogeneic Hematopoietic Cell Transplantation Recipients.

Gavriilaki E, Bousiou Z, Batsis I, Vardi A, Mallouri D, Koravou E Int J Mol Sci. 2024; 25(1).

PMID: 38203404 PMC: 10778584. DOI: 10.3390/ijms25010231.


Medical consult: aHUS, TTP? How to distinguish and what to do.

Story C, Gerber G, Chaturvedi S Hematology Am Soc Hematol Educ Program. 2023; 2023(1):745-753.

PMID: 38066937 PMC: 10727109. DOI: 10.1182/hematology.2023000501.


References
1.
Noris M, Galbusera M, Gastoldi S, Macor P, Banterla F, Bresin E . Dynamics of complement activation in aHUS and how to monitor eculizumab therapy. Blood. 2014; 124(11):1715-26. PMC: 4162105. DOI: 10.1182/blood-2014-02-558296. View

2.
Loirat C, Garnier A, Sellier-Leclerc A, Kwon T . Plasmatherapy in atypical hemolytic uremic syndrome. Semin Thromb Hemost. 2010; 36(6):673-81. DOI: 10.1055/s-0030-1262890. View

3.
Cataland S, Wu H . Diagnosis and management of complement mediated thrombotic microangiopathies. Blood Rev. 2014; 28(2):67-74. DOI: 10.1016/j.blre.2014.01.003. View

4.
Marinozzi M, Vergoz L, Rybkine T, Ngo S, Bettoni S, Pashov A . Complement factor B mutations in atypical hemolytic uremic syndrome-disease-relevant or benign?. J Am Soc Nephrol. 2014; 25(9):2053-65. PMC: 4147975. DOI: 10.1681/ASN.2013070796. View

5.
Frimat M, Tabarin F, Dimitrov J, Poitou C, Halbwachs-Mecarelli L, Fremeaux-Bacchi V . Complement activation by heme as a secondary hit for atypical hemolytic uremic syndrome. Blood. 2013; 122(2):282-92. DOI: 10.1182/blood-2013-03-489245. View