232. Complement Activation during Remission in ANCA-Associated Vasculitis
Creators: name: Maria Iordanou1, 3
name: Rebecca Trattner Evetovics2, 4
name: Hellmark1, Thomas
name: Myriam Martin2, 4
name: Sophie  Ohlsson1, 3
name: Anna Blom2, 4
name: Mårten Segelmark1, 3
Publisher: name: Zenodo
Year: 2022
Subjects: Vasculitis
ANCA
Abstracts
Giant Cell Arthritis
MPA
GPA
EGPA
Takayasu
IgA vasculitis

description: <strong>Background: </strong> Experimental and clinical observations have shown that the complement system is crucial for the pathogenesis of ANCA-associated vasculitis (AAV), and the development of new drugs has put emphasis on the complement inhibition. Previous studies have shown that complement activation is common not only during relapse but also during remission, but the origin and importance of this is largely unknown. The aim with this study is to investigate if complement activation during stable remission is an indicator of upcoming relapses and to study clinical correlates to the activation through the classical, alternative, or terminal pathways. <strong>Methods:</strong> During 2015-2018, there were selected 206 plasma samples from 81 patients with GPA or MPA and preserved in -80°C. BVAS at the date of sampling was used to categorize the samples as remission samples, and those were further divided into samples with and without subsequent relapses. C4d is a sub-product of C4, that is a component of the classical and lectin pathways. C3bBbP is a C3 convertase from the alternative pathway, and sTCC (soluble terminal complement complex) is the final component of general complement activation. Sandwich ELISA using monoclonal antibodies specific for those complement activation products were analysed in all samples. <strong>Results:</strong> The levels of C4d, C3bBbP and TCC were higher in many, but not all patients with AAV during remission, compared to the levels from healthy controls. TCC was correlated with both C4d and C3BbP, but there was no correlation in between C4d and C3bBbP. While 44 patients had at least one relapse, 37 of the patients had no relapses during the follow-up. There were no significant differences in the levels of complement activation products between samples taken from patients that had at least one subsequent relapse and from patients that had no relapses until the end of the follow-up, which was 3-5 years. Similarly, patients with multiple relapses did not have higher levels of the complement activation products compared to those who had one or those with no relapses. On the other hand, there was a positive correlation between levels of TCC and creatinine, but there was no correlation in between C4d and C3bBbP with creatinine levels. Patients with no or low dose of corticosteroids (&lt;5 mg/day) had higher levels of C4d, which indicates that corticosteroids supress the activation through the classical pathway. There was no correlation in between complement levels and other immunosuppressive drugs. <strong>Conclusions:</strong> Complement activation products cannot be used as biomarkers for predicting relapse in AAV, based on the results from this study. Higher levels of TCC are correlated with low GFR, suggesting that organ damage or damage to the vasculature can be reflected in complement activation products. Corticosteroids seem to suppress activation of the classical pathway in AAV, which might be an important mode of action for these agents to prevent relapse. <strong>Disclosures:</strong> Anna Blom is the inventor in a patent application that comprises claims for using C4d as a biomarker. The other authors declare no conflicts of interest.