Role of complement in the pathogenesis of thrombotic microangiopathies

Trojnár, Eszter; Szilágyi, Ágnes; Mikes, Bálint; Csuka, Dorottya; Sinkovits, György; Prohászka, Zoltán

doi:10.1007/s12254-017-0380-y

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“…Both acute and chronic kidney damage have been linked to the elevation of PTX3 (35), the lack of which in TTP could provide a possible explanation for the absence of PTX3 elevation in TTP. However, it cannot be excluded that additional factors arising from the distinct pathogenesis of TTP (34) have also contributed to the observed difference.…”

Section: Discussionmentioning

confidence: 96%

“…In approximately 60% of aHUS cases mutations to the complement genes or antibodies directed against the complement regulator FH account for the pathophysiological process leading to AP dysregulation and consumption (33, 34), whereas in the remaining one-third of the cases the molecular background remains unrevealed. Our aHUS cohort had a somewhat higher representation of autoimmune aHUS (25 vs. 10%) and a relatively small proportion of unexplained cases (25 vs. 30–40%) compared to the previously reported prevalence (33, 34). We had a notable number of patients with low FH level in our patient cohort.…”

Section: Discussionmentioning

confidence: 99%

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Elevated Systemic Pentraxin-3 Is Associated With Complement Consumption in the Acute Phase of Thrombotic Microangiopathies

et al. 2019

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Pentraxin-3 (PTX3) and C-reactive protein (CRP) have been shown to regulate complement activation in vitro , but their role has not been investigated in complement consumption in vivo . Thrombotic microangiopathies (TMA) are often accompanied by complement overactivation and consumption, therefore we analyzed the relation of the systemic pentraxin levels to the complement profile, laboratory parameters and clinical outcome of TMA patients. We determined the PTX3 and CRP levels, complement factor and activation product concentrations in blood samples of 171 subjects with the diagnosis of typical hemolytic uremic syndrome (STEC-HUS) ( N = 34), atypical HUS (aHUS) ( N = 44), secondary TMA ( N = 63), thrombotic thrombocytopenic purpura (TTP) ( N = 30) and 69 age-matched healthy individuals. Clinical data, blood count and chemistry were collected from medical records. To determine the in vitro effect of PTX3 on alternative pathway (AP) activation, sheep red blood cell-based hemolytic assay and AP activity ELISA were used. We found that PTX3 levels were elevated in the acute phase of STEC-HUS, aHUS and secondary TMA, whereas PTX3 elevation was exceptional is TTP. Conversely, a significantly higher median CRP was present in all patient groups compared to controls. PTX3, but not CRP was associated with signs of complement consumption in vivo , and PTX3 significantly decreased the AP hemolytic activity in vitro . Our results provide a detailed description of acute phase-TMA patients' complement profile linked to changes in the systemic pentraxin levels that may support further molecular studies on the function of PTX3 in disease pathogenesis and add to the laboratory assessment of complement consumption in TMA.

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Section: Discussionmentioning

confidence: 96%