High-Sensitivity C-Reactive Protein (hs-CRP) and Pentraxin 3 (PTX3) Are Increased in Essential Thrombocythemia and Polycythemia Vera.
Authors: Barbui Tiziano , Carobbio Alessandra , Bottazzi Barbara , Zilio Pio , Salvi Anna , Cuccovillo Ivan , Salmoiraghi Silvia , Finazzi Guido , Mantovani Alberto , Rambaldi Alessandro 
Published: October 2019

Abstract
Abstract 1911
Poster Board I-934

Background:
The role of inflammation in the pathogenesis of the athero-thrombosis has become well established over the past decade. In general population, markers of inflammation are associated with cardiovascular events and predictors of future thrombosis are leukocyte (WBC) count and short and long pentraxins such as high-sensitivity C-reactive protein (hs-CRP) and pentraxin 3 (PTX3). In Polycythemia Vera (PV) and Essential Thrombocythemia (ET), WBC count has been related to major vascular complications and there is evidence that this association can be mediated by JAK2V617F mutation. We tested the hypothesis that plasma levels of hs-CRP and PTX3 can be increased in patients with ET and PV following the permanent and constitutive inflammatory state as revealed by leukocytosys and leukocyte activation. This would further support the idea that an underpinning latent chronic inflammation may contribute to the thrombotic propensity of these clonal myeloproliferative disorders.

Methods and Results:
Plasma level concentrations of hs-CRP and PTX3 were tested in the same samples of 48 PV and 52 ET patients (WHO 2008 diagnostic criteria) obtained at different times from diagnosis when patients were receiving aspirin alone (21% of ET and 37% of PV) or cytoreduction in 33% (hydroxyurea in 28%) alone or combined with aspirin in 38% of ET and 27% of PV. Twenty-two percent of ET and PV patients remained untreated and were submitted to phlebotomy according to hematocrit levels. Plasma levels of hs-CRP were measured by a commercially available immunoturbidimetric method (ADVIA 2400 Chemistry CardioPhaseTM, Siemens Healthcare Diagnostics Inc., Tarrytown, NY, US) while PTX3 was measured with a sandwich ELISA based on a monoclonal antibody (mAb) MNB4 (ascites diluted 1:5000 in coating buffer) and rabbit antiserum (Peri et al.: Circulation 2000, Latini et al.: Circulation 2004). The median age of ET and PV patients was 61 years (range: 32-87) and 62 years (range: 33-87), respectively. In 32 normal healthy controls median concentration of hs-CRP was 0.57 mg/L (range: 0.1-2.86). In 52 ET cases median hs-CRP values were not statistically different (median: 0.83 mg/L; range: 0.26-57.69, p=0.43). On the contrary, the 48 PV patients showed a significant increment (p=0.012) of hs-CRP concentration (median 1.31 mg/L; range: 0.15-53.36). The same results were found for PTX3: ET patients exhibited plasma values (median: 1.91; range: 0.8-7.75) not different (p=0.16) from controls (median: 1.74; range: 0.45-2.9) while in PV (median: 2.74; range: 0.33-10.83) the difference was statistically significant (p=0.012). Overall, hs-CRP and PTX3 values above the normal range were found in around a quarter of PV and ET patients. The distribution of clinical and hematological variables by hs-CRP plasma value tertiles (cut-off: <0.65; 0.65-1.88; >1.88) showed a significant correlation with JAK2V617F granulocyte allele burden (p= 0.004) while this correlation was weaker for PTX3 (p= 0.05). Similarly, lower, middle and upper tertiles for PTX3 were calculated (cut-off: <1.68; 16-.68-3.04; >3.04, respectively) and, in contrast to hs-CRP, the highest PTX3 tertile was associated with older age (p=0.001) and the PV phenotype (p=0.02). Both in ET and PV the other variables, including sex, hemoglobin, hematocrit, white blood cell and platelet count as well as treatments, did not show different distribution by hs-CRP and PTX3 tertiles. Vascular complications (32 episodes, calculated in the history, at diagnosis and in follow-up) were equally registered in the tertiles both in ET and PV.

Conclusion:
The present study is the first to show that both in ET and PV, blood hs-CRP and PTX3 are significantly increased mainly in relation to JAK2V617F mutation and age, and further supports the idea that in these disorders an underpinning latent chronic inflammation is demonstrable. Therefore, it is conceivable that these inflammatory pentraxins may contribute to vascular complications of these clonal disorders. Nevertheless, this preliminary information needs to be validated in a larger study.

Disclosures:
No relevant conflicts of interest to declare.