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Glycoprotein VI identified as potential target for antibody-mediated platelet activation in RA

This provides further in vivo evidence that the GPVI pathway is involved in antibody-mediated platelet activation in humans. 

The importance of platelet activation in RA pathogenesis is increasingly recognised.

A number of auto-antibodies, including anti-citrullinated protein antibodies (ACPA), have been shown to cause platelet activation in vitro, through the low-affinity immunoglobulin G (IgG) receptor (FcgRIIa) on platelets. 

Platelet activation via engagement of FcgRIIa results in proteolytic cleavage and shedding of platelet-specific glycoprotein VI (GPVI), which can be detected in the plasma as soluble GPVI (sGPVI).

The aim of the study, according to Dr John Stack of the Mater Hospital, Dublin, who made the presentation to the Meeting, was to prove that plasma levels would be increased among patients with seropositive RA as a consequence of antibody-induced platelet activation and GPVI shedding. 

Samples from 84 patients with RA (65 seropositive and 19 seronegative) and 67 healthy controls were collected prospectively and analysed for sGPVI using a standardised ELISA.

According to the findings, sGPVI correlated significantly with both ACPA and RF.

Dr Stack reported that no correlation was observed between sGPVI and age, ES, CRP, DAS-28, platelet count or fibrinogen. 

“In summary, this is the first in vivo study to identify an association between sGPVi, a marker of platelet activation in humans,” Dr Stack concluded.

“It provides evidence that ITAM-based signalling via engagement of either GPVI or FcgRlla results in shedding of GPVI and platelet activation.”

Another oral presentation from staff at the University of Limerick and University Hospital Limerick was on the subject of Behcet’s disease (BD) in Ireland.

The disease causes blood vessel inflammation throughout the body and can lead to numerous signs and symptoms, which may include mouth sores, eye inflammation, skin rashes and lesions, and genital sores.

According to the conclusion of the study, which examined the prevalence, clinical manifestations and management of the condition: “The prevalence of BD in Ireland is higher than previously reported in the region, consistent with the current literature that the prevalence is gradually increasing globally. Its management requires long-term multidisciplinary involvement. 

No patients on conventional DMARDs alone achieved full remission. The percentage of our BD patients treated with the anti-TNF is higher compared to other countries and we acknowledge that it is an important alternative option in patients with severe or life-threatening manifestations.”

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