PhD Scientific Days 2024

Poster Session M - Cardiovascular Medicine and Research 1.

Cytokine Patterns of Thrombotic Thrombocytopenic Purpura (TTP) and COVID-19

Text of the abstract

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy characterized by life-threatening acute episodes alternating with phases of remission. Recently, the concept of immunothrombosis (IT) has emerged as a driving force of several diseases including TTP and COVID-19. Cytokines are vital regulators of inflammation, thus the analysis of their patterns is crucial to understand immunothrombotic diseases (ITDs). Unlike the extensive research on the COVID-19 cytokine storm, limited data exists on the baseline cytokine patterns of TTP patients, with no studies directly comparing remission to acute phase, making it our primary focus. Moreover, we aimed to compare cytokine patterns of TTP and COVID-19 to identify disease-specific or general IT characteristics.
Plasma concentrations of 33 soluble mediators (SMs: cytokines, chemokines, soluble receptors and growth factors) were measured by bead-based LEGENDplex™ analysis, using 3 commercially available kits. We collected 80 cytrate plasma samples: 32 from COVID-19 patients divided into 3 severity groups (12 Covid 2: hospitalized, no O2 need; 13 Covid 3: hospitalized, O2 on nasal cannula/mask; 7 Covid 4: intensive care unit), 32 TTP sample pairs from 16 patients in remission and acute phases, and 16 healthy controls. Statistical analyses included the Mann-Whitney, Wilcoxon, or Jonckheere tests, and principal component analysis (PCA).
6 SMs, mainly governing the adaptive immune response, were undetectable in all patient groups. In TTP, 11 SMs (mainly inflammatory cytokines) decreased in both remission and the acute phase, while 1 decreased and two elevated only in the latter. In COVID-19, 12 key proinflammatory SMs increased (with 11 showing a severity trend), while 3 decreased with severity trend. In severe COVID-19, 18 SMs exceeded acute TTP levels, with just 1 was higher in acute TTP. PCA identified CXCL10, IL-1RA, VEGF, STREM-1, IL-18 and CCL4 as the main discriminators between the two groups.
Adaptive immunity appears to be less engaged than the innate response in both COVID-19 and TTP. Despite categorizing TTP as an ITD, its cytokine pattern suggests a distinct pathomechanism from COVID-19. Our findings support labeling TTP as thromboinflammatory rather than immunothrombotic (as in COVID-19), to highlight thrombosis rather than inflammation as the driving force.

Supported by HUN-REN-SU.