Complement factor B expression profile in a spontaneous uveitis model.
Abstract: Equine recurrent uveitis serves as a spontaneous model for human autoimmune uveitis. Unpredictable relapses and ongoing inflammation in the eyes of diseased horses as well as in humans lead to destruction of the retina and finally result in blindness. However, the molecular mechanisms leading to inflammation and retinal degeneration are not well understood. An initial screening for differentially regulated proteins in sera of uveitic cases compared to healthy controls revealed an increase of the alternative pathway complement component factor B in ERU cases. To determine the activation status of the complement system, sera were subsequently examined for complement split products. We could demonstrate a significant higher concentration of the activation products B/Ba, B/Bb, Bb neoantigen, iC3b and C3d in uveitic condition compared to healthy controls, whereas for C5b-9 no differences were detected. Additionally, we investigated complement activation directly in the retina by immunohistochemistry, since it is the main target organ of this autoimmune disease. Interestingly, infiltrating cells co-expressed activated factor Bb neoantigen, complement split product C3d as well as CD68, a macrophage marker. In this study, we could demonstrate activation of the complement system both systemically as well as in the eye, the target organ of spontaneous recurrent uveitis. Based on these novel findings, we postulate a novel role for macrophages in connection with complement synthesis at the site of inflammation.
Publication Date: PubMed ID: 20334949
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Summary
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The research article focuses on understanding the role of complement factor B in equine recurrent uveitis, a condition that serves as a model for human autoimmune uveitis. Increased concentration of complement component factor B was discovered in affected cases, leading to postulations about the role of macrophages in the synthesis of this element at inflammation sites.
Understanding Uveitis and Equine Recurrent Uveitis
- Uveitis is an inflammatory condition affecting the eyes, which can eventually lead to blindness due to retina destruction. Its triggers remain unpredictable leading to recurrent episodes.
- To better understand human autoimmune uveitis, this study utilizes equine recurrent uveitis (ERU) as a spontaneous model. This choice stems from the similarities in symptoms and progression of the disease in both horses and humans.
Screening process and Results
- The researchers began their study by differentially screening for regulated proteins in the blood samples (sera) of uveitic cases as compared to healthy controls. Throughout this process, they noticed an increase in the complement component factor B in samples from ERU cases.
- Subsequent examination of the sera for complement split products aimed to establish the activation status of the complement system. Observations were made for significantly higher concentrations of activation products B/Ba, B/Bb, Bb neoantigen, iC3b and C3d in uveitic cases than in healthy controls. C5b-9 split products, however, showed no difference.
- The team also investigated complement activation in the retina, as it is the most affected organ in this autoimmune disease, using immunohistochemistry. They noted that infiltrating cells co-expressed activated factor Bb neoantigen, complement split product C3d, and CD68, a marker for macrophages (immune cells).
Interpretations and Postulations
- The study demonstrated activation of the complement system both systemically and specifically within the eye, which is the primary target of recurrent uveitis.
- Based on the findings, the researchers cogitated that macrophages might play a new role in the synthesis of complement at the site of inflammation, possibly exacerbating the disease progression.
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Complement factor B expression profile in a spontaneous uveitis model.
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