scholarly journals Soluble glycoprotein VI, a specific marker of platelet activation is increased in the plasma of subjects with seropositive rheumatoid arthritis

PLoS ONE ◽  
2017 ◽  
Vol 12 (11) ◽  
pp. e0188027 ◽  
Author(s):  
John R. Stack ◽  
Anne Madigan ◽  
Laura Helbert ◽  
Eimear Dunne ◽  
Elizabeth E. Gardiner ◽  
...  
Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Geraint A Brown ◽  
Louise Kearney ◽  
Elizabeth Warner ◽  
Spencer Ellis

Abstract Background/Aims  Disease-modifying anti-rheumatic drugs (DMARDs) require blood monitoring as recommended by the British Society for Rheumatology guidelines. Deranged liver function tests are a common abnormality, and when a significant transaminitis occurs further investigations are required. We wish to present three cases where a transaminitis was caused by acute hepatitis E. Hepatitis E rarely causes illness in the general population. Transmission can occur via sewage-contaminated food and water, undercooked or raw pig and game meat, or processed pork and shellfish. Blood transfusion and solid organ transplantation is very rare. There is an estimated 60,000 cases of Hepatitis E per year in England. Those who are immunosuppressed are more likely to develop chronic liver disease. Methods  . Results  Case 1 is 55 year old male with a seronegative inflammatory arthritis treated with methotrexate and sulfasalazine whose ALT rose to 2043 U/l. After a negative liver screen including autoantibodies, Hepatitis E IgM was detected. Case 2 is a 71 year old male with seropositive rheumatoid arthritis prescribed Methotrexate and Sulfasalazine who developed a transaminitis following a holiday to Spain. Hepatitis E serology was positive. Case 3 is a 65 year old male with seropositive rheumatoid arthritis on Abatacept and Methotrexate who also developed deranged liver function tests following a trip to Spain. Alcohol excess was initially suspected due to the consumption of > 20 units per week. However, on cessation of all medications the ALT continued to rise to 1087 U/l. He was found to be Hepatitis E IgM positive with viral PCR also detected. In all three cases contaminated food was likely to be the source of infection and DMARDs were successfully restarted in all patients following normalisation of liver function tests. Conclusion  This case series highlights an important differential for transaminitis with very little published literature. Hepatitis E is under reported and not routinely requested in practice as part of a liver screen. Failure to check Hepatitis E serology may lead to DMARDs being discontinued inappropriately. All patients should be educated about the risks of Hepatitis E from food products.We recommend that DMARDs are suspended once Hepatitis E infection has been diagnosed in order to allow the immune system combat the infection. Treatment is usually self limiting, though in severe cases Ribavirin has been used with good effect. DMARDs should be restarted once liver markers normalise, and two serum Hepatitis E RNA results and two stool samples are negative. The presence of persistent Hepatitis E RNA (viral shedding) is highly suspicious for chronic infection, which would warrant hepatology input. Disclosure  G.A. Brown: None. L. Kearney: None. E. Warner: None. S. Ellis: None.


Blood ◽  
2012 ◽  
Vol 119 (15) ◽  
pp. 3613-3621 ◽  
Author(s):  
C. Y. Eleanor Fung ◽  
Sarah Jones ◽  
Adwoa Ntrakwah ◽  
Khalid M. Naseem ◽  
Richard W. Farndale ◽  
...  

Abstract Inhibition of Ca2+ mobilization by cyclic nucleotides is central to the mechanism whereby endothelial-derived prostacyclin and nitric oxide limit platelet activation in the intact circulation. However, we show that ∼ 50% of the Ca2+ response after stimulation of glycoprotein VI (GPVI) by collagen, or of Toll-like 2/1 receptors by Pam3Cys-Ser-(Lys)4 (Pam3CSK4), is resistant to prostacyclin. At low agonist concentrations, the prostacyclin-resistant Ca2+ response was predominantly because of P2X1 receptors activated by ATP release via a phospholipase-C–coupled secretory pathway requiring both protein kinase C and cytosolic Ca2+ elevation. At higher agonist concentrations, an additional pathway was observed because of intracellular Ca2+ release that also depended on activation of phospholipase C and, for TLR 2/1, PI3-kinase. Secondary activation of P2X1-dependent Ca2+ influx also persisted in the presence of nitric oxide, delivered from spermine NONOate, or increased ectonucleotidase levels (apyrase). Surprisingly, apyrase was more effective than prostacyclin and NO at limiting secondary P2X1 activation. Dilution of platelets reduced the average extracellular ATP level without affecting the percentage contribution of P2X1 receptors to collagen-evoked Ca2+ responses, indicating a highly efficient activation mechanism by local ATP. In conclusion, platelets possess inhibitor-resistant Ca2+ mobilization pathways, including P2X1 receptors, that may be particularly important during early thrombotic or immune-dependent platelet activation.


2013 ◽  
Vol 305 (12) ◽  
pp. C1230-C1239 ◽  
Author(s):  
Joseph E. Aslan ◽  
Kevin G. Phillips ◽  
Laura D. Healy ◽  
Asako Itakura ◽  
Jiaqing Pang ◽  
...  

The tubulin cytoskeleton plays a key role in maintaining the characteristic quiescent discoid shape of resting platelets. Upon activation, platelets undergo a dramatic change in shape; however, little is known of how the microtubule system contributes to regulating platelet shape and function. Here we investigated the role of the covalent modification of α-tubulin by acetylation in the regulation of platelet physiology during activation. Superresolution microscopy analysis of the platelet tubulin cytoskeleton showed that the marginal band together with an interconnected web of finer tubulin structures collapsed upon platelet activation with the glycoprotein VI (GPVI)-agonist collagen-related peptide (CRP). Western blot analysis revealed that α-tubulin was acetylated in resting platelets and deacetylated during platelet activation. Tubacin, a specific inhibitor of the tubulin deacetylase HDAC6, prevented tubulin deacetylation upon platelet activation with CRP. Inhibition of HDAC6 upregulated tubulin acetylation and disrupted the organization of the platelet microtubule marginal band without significantly affecting platelet volume changes in response to CRP stimulation. HDAC6 inhibitors also inhibited platelet aggregation in response to CRP and blocked platelet signaling events upstream of platelet Rho GTPase activation. Together, these findings support a role for acetylation signaling in controlling the resting structure of the platelet tubulin marginal band as well as in the coordination of signaling systems that drive platelet cytoskeletal changes and aggregation.


2020 ◽  
Vol 16 (2) ◽  
pp. 336
Author(s):  
Seojun Im ◽  
Min Ok Kim ◽  
Soo-Kyoung Kim ◽  
Heejeong Jeong ◽  
Heeyoung Kang

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