Evidence for Alternative Complement Cascade Activation in Primary CNS Vasculitis
| Autor: | Rula A. Hajj-Ali, Caleigh Mandel-Brehm, Jennifer Madan Cohen, Alex Yamana, Joseph L. DeRisi, Antoine G. Sreih, Giselle M. Knudsen, Hanna Retallack, Leonard H. Calabrese, Jeffrey M. Gelfand, Michael R. Wilson, Tarik Tihan, Kelsey C. Zorn, Hannah A. Sample, S. Andrew Josephson, Vanja C. Douglas, Mark P. Gorman, Jacqueline F. Marcus |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Complement component 5
0303 health sciences business.industry Central nervous system Meninges Inflammation medicine.disease 3. Good health Complement system 03 medical and health sciences 0302 clinical medicine Cerebrospinal fluid medicine.anatomical_structure Immunology Alternative complement pathway Medicine medicine.symptom business Vasculitis 030217 neurology & neurosurgery 030304 developmental biology |
| DOI: | 10.1101/329862 |
| Popis: | The central nervous system (CNS) has a dedicated network of blood vessels to support the physiological activity of the brain, spinal cord and meninges. Consequently, inflammation of CNS vasculature can have devastating effects on neurological function. A lack of understanding regarding the molecular pathology of CNS vasculitis impedes the development of better diagnostics and effective therapies. Here, we analyze the proteome of cerebrospinal fluid from patients with biopsy-confirmed Primary Angiitis of the Central Nervous System (PACNS) relative to non-inflammatory control patients and patients with Reversible Cerebral Vasoconstrictive Syndrome (RCVS), a syndrome that clinically mimics PACNS in several aspects. In PACNS, we find significant elevation of apolipoproteins, immunoglobulins and complement cascade components. Notably, we find a bias towards activation of the alternative complement pathway with elevated levels of the terminal cascade component, complement C5. Given the recent treatment successes of Anti-Neutrophil Cytoplasmic Antibody (ANCA) vasculitis with the C5 receptor inhibitor, CCX168 (Avacopan), our results suggest that complement C5 inhibitors may also prove useful as therapeutic interventions for PACNS. |
| Databáze: | OpenAIRE |
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