PhD Scientific Days 2019

Budapest, April 25–26, 2019

Identification of a novel pathogenic factor in atypical hemolytic uremic syndrome

Janszky, Noémi

Noémi Janszky1, Edina Szabó1, Beáta Takács1, Ágnes Szilágyi1, Zoltán Prohászka1, Dorottya Csuka1
1 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary

Language of the presentation

Hungarian

Text of the abstract

Introduction: Atypical hemolytic uremic syndrome (aHUS) is a clinical syndrome, which belongs to a group of thrombotic microangiopathies. In most cases the underlying cause of aHUS is an uncontrolled activation of the complement system. Mutations and polymorphisms in the complement system regulating proteins and components represent increased risk factors. However previous studies reported that these known mutations are identified in only 60-70 % of the aHUS cases.
Aim: Therefore, the aim of our study was to identify novel pathogenic factors. As the first candidate, another member of the regulators of complement activation (RCA) gene cluster on chromosome I, Factor XIII was chosen.
Methods: 30 aHUS patients and 14 healthy controls were involved in our study. For screening the mutations and polymorphisms in genes encoding A and B subunits of factor XIII, high resolution melting analysis (HRM) was utilized. The identified variations were verified by DNA sequencing. Activity of factor XIII in both aHUS patients and healthy controls was defined by a commercial kit using citrated plasma.
Results: After performing DNA sequencing on F13A1 and F13B exons from aHUS patients and healthy controls, HRM was standardized. In two sibling aHUS patients and also in their healthy father an AAC triplet insertion (c.300_302insAAC) was indentified in the exon 3 of F13B, which resulted in decreased activity of factor XIII. Moreover, compared to healthy controls (119±31%), we found a significantly decreased FXIII activity in patients with both acute (69±36%, p=0.0051) and remission stages (93±35, p=0.046) of aHUS.
Conclusion: Our results indicate that in aHUS patients factor XIII activity correlates with the activity of microangiopathic processes. Furthermore, rare genetic mutations of F13B can emerge as underlying causes for the decreased factor XIII activity.

Data of the presenter

Doctoral School: Basic and Translational Medicine
Program: Vascular Pathophysiology / Atherosclerosis
Supervisor: Csuka Dorottya
E-mail address: janszkynoemi@gmail.com