Small Particles Produced by Platelets May Worsen Inflammation in AAV, Study Contends

Small Particles Produced by Platelets May Worsen Inflammation in AAV, Study Contends

Platelet-derived microparticles (PMPs) — small particles produced and released by platelets in the blood — may worsen inflammation in patients with ANCA-associated vasculitis, according to a recent study.

The findings of the study, “Platelets release proinflammatory microparticles in anti-neutrophil cytoplasmic antibody-associated vasculitis,” were published in Rheumatology.

Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, or AAV, is an autoimmune disease caused by the production of autoantibodies — antibodies that wrongly target and attack healthy cells — leading to blood vessel inflammation and swelling in affected tissues and organs.

In a previous study, the same team of researchers showed that platelets (small particles responsible for blood clotting) are overactive in AAV patients, leading to an over-activation of the complement system — a set of more than 50 blood proteins that form part of the body’s immune defenses — and tissue inflammation.

“Many studies have reported the increased level of platelet-derived microparticles (PMPs) in inflammatory diseases, including RA [rheumatoid arthritis], SLE [systemic lupus erythematosus] and IBD [inflammatory bowel disease], in which the increase in microparticles (MPs) is associated with disease severity,” the investigators wrote. However, no study so far has addressed the role of PMPs in patients with AAV.

In this study, a team of Chinese researchers set out to investigate the role of PMPs in a group of patients with active AAV.

The study involved 69 AAV patients with active disease — 87 in remission, and 109 healthy controls. Researchers measured the total levels of PMPs in AAV patients’ blood, as well as the levels of 640 different proteins produced by active platelets. All data was correlated with patients’ clinical data.

Results showed the total levels of PMPs increased significantly in AAV patients with active disease (4406.8/μl), especially in those who tested positive for myeloperoxidase (MPO) ANCA autoantibodies, compared to those who were in remission (549.7/μl) or healthy controls (264.9/μl). In addition, 43% of all microparticles found in patients with active AAV were PMPs.

Researchers also found that platelets’ microparticles from AAV patients with active disease contained high levels of pro-inflammatory molecules, compared to AAV patients in remission, suggesting that PMPs might be promoting tissue inflammation.

Further correlation analysis confirmed that the proteins within PMPs were involved in  migration, adhesion, growth, and cell death, and that the amount of PMPs in the patients’ blood was directly correlated with disease activity, inflammation, and kidney damage.

“[O]ur study revealed that increased levels of MPs from platelets may be actively involved in enhancing an acute inflammatory state in AAV. Thus, we have developed some concepts for potential functions of PMPs by [analyzing] various MPs, comparing numerous pro-inflammatory cytokines, and integrating multiple clinical parameters, thus opening up potentially new avenues for treatment,” the scientists concluded.

Joana holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from Universidade de Lisboa. She is currently finishing her PhD in Biomedicine and Clinical Research at Universidade de Lisboa. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells — cells that made up the lining of blood vessels — found in the umbilical cord of newborns.
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Joana holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from Universidade de Lisboa. She is currently finishing her PhD in Biomedicine and Clinical Research at Universidade de Lisboa. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells — cells that made up the lining of blood vessels — found in the umbilical cord of newborns.
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