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. 2022 Dec:220:121-124.
doi: 10.1016/j.thromres.2022.10.011. Epub 2022 Oct 22.

The homophilic CD84 receptor is upregulated on platelets in COVID-19 and sepsis

Lukas J Weiss  1 , Maria Drayss  1 , Kristina Mott  2 , Margret Droste  2 , Bastian Just  2 , Anna M Arold  2 , Bernhard Nieswandt  3 , Dirk Weismann  4 , David Stegner  3 , Harald Schulze  5
Affiliations

The homophilic CD84 receptor is upregulated on platelets in COVID-19 and sepsis

Lukas J Weiss et al. Thromb Res. 2022 Dec.
No abstract available

Keywords: CD84; COVID-19; Platelets; Sepsis; Thrombo-inflammation.

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Conflict of interest statement

Declaration of competing interest BN and DS have filed a patent (PCT/EP/2020/068464) related to targeting CD84 as treatment option in ischemic diseases. All other authors do not declare any conflict of interest.

Figures

Fig. 1
Fig. 1
(A) Platelets of patients with sepsis (s) or COVID-19 showed highly increased CD84 surface expression at 4 different time points over the disease (t1 = day of ICU admission; t2 = d4; t3 = d7, t4 = d14). (B) CD84 expression in COVID-19 patients was independent of platelet size indicated by mean platelet volume (MPV) (C-D) CD84 expression was analyzed by immunoblot in lysates of healthy controls and COVID-19 patients. CD84 signal intensity was set in relation to GAPDH. (E-F) CD84 expression on megakaryocytes (day 9) derived from human CD34+ cells upon co-incubation with platelet poor plasma (3 %) from sepsis patients or controls. (G-H) CD84 shedding was observed in COVID-19 patients upon CCCP [100 μM] stimulation for 60 min at 37 °C but not upon TRAP-6 stimulation [5 μM]. Metalloproteinase inhibitor GM6001 [100 μM] prevented CD84 shedding. (I-J) CD84 expression on neutrophils (CD45+/CD15+) or lymphocytes (CD3+/CD8; CD3+/CD8+) was assessed flow cytometrically. (K) Formation of platelet leukocyte-aggregates (PLA: CD41+/CD45+) and CD84 expression were assessed flow cytometrically and the values correlated by calculation of Pearson's r. (L) Platelets of healthy donors were incubated for 2 h at 37 °C in platelet-poor plasma or (M-N) whole blood of allogenous healthy controls or COVID-19 patients prior to measuring platelet CD84 expression flow cytometrically. Representative curves are shown in panel C, E, G, I and M. Scale bars indicate 60 μM in panel E. Data is indicated as median ± 95 % CI. Statistical analysis was performed using (A) Kruskal-Wallis test, (E) paired t-test or (K, L, N) Mann-Whitney test. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.
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