Discovery of Key Proteins Associated with Rare Autoimmune Vasculopathy
Researchers have identified two proteins, CCN1 and CCN2, that play a crucial role in blood vessel thickening in autoimmune vasculopathy, a complication of antiphospholipid syndrome, opening new avenues for targeted treatments.
Recent research has shed light on the molecular mechanisms underlying antiphospholipid syndrome (APS), a rare autoimmune disorder affecting approximately 1 in 2,000 individuals. APS is primarily known for increasing the risk of blood clots, such as deep vein thrombosis and strokes. However, an often underestimated complication is APS vasculopathy, which impacts 10-20% of patients by causing abnormal thickening of blood vessel walls, leading to narrowing of the vessel lumen. This process compromises blood flow, especially in small vessels supplying vital organs like the kidneys, heart, and skin, potentially resulting in organ damage and failure.
A groundbreaking study led by Dr. Jason Knight at the University of Michigan utilized skin biopsies from patients with severe APS to investigate the disease at a cellular level using single-cell sequencing. The researchers identified two proteins, CCN1 and CCN2, that were significantly overexpressed in blood vessel cells of APS patients. These proteins are known for their roles in tissue scarring (fibrosis), but in this context, they appear to promote the proliferation of endothelial and smooth muscle cells within blood vessel walls. This proliferation thickens the vessel walls and reduces blood flow.
Among the two proteins, CCN2 demonstrated a particularly strong influence on vascular cell behavior, suggesting it as a promising target for future therapies. Although biologic drugs targeting CCN2 are already available, researchers emphasize the need for further clinical trials specifically for APS treatment. Additionally, the study revealed that overexpression of CCN1 and CCN2 is also evident in kidney tissues of APS patients, indicating that skin biopsies might serve as accessible indicators of deeper organ involvement.
The findings pave the way for developing innovative treatments aimed at preventing organ deterioration caused by APS vasculopathy. Dr. Shi highlighted the importance of ongoing efforts to monitor patient cohorts over time, which will help understand disease progression and facilitate the design of effective clinical trials. This research marks a significant step toward targeted therapies that could mitigate the severe complications associated with APS.
Source: https://medicalxpress.com/news/2025-09-key-proteins-rare-autoimmune-disease.html
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