THU0315 THE CLINICAL RELEVANCE OF SERUM IMMUNE COMPLEXES IN ANCA-ASSOCIATED VASCULITIS
Authors: M. Okamoto, K. Ichinose, K. Oyama, K. E. Sada, S. Y. Kaname, M. Harigai, A. Kawakami
Journal: Annals of the Rheumatic Diseases (2020)

Background: AAV is an autoimmune disease characterized by systemic vasculitis and pauci-immune-type crescentic glomerulonephritis (CGN) with ANCA production 1) . Several authors have reported cases of ANCA-associated CGN with definite IC deposits 2)3) , however, the clinical significance of IC in patients with ANCA-associated CGN remains unclear. Objectives: To investigate the clinical relevance of serum immune complexes (ICs) in ANCA-associated vasculitis (AAV) patients. Methods: We developed a novel proteomic strategy for identifying and profiling antigens in immune complexes in the serum of microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) patients. The serum was collected from the cohort of Japan Research Committee of the Ministry of Health Labour, Welfare for Intractable Vasculitis (JPVAS) before treatment and 6 months after initiation of treatment. The serum from healthy individuals was used for control samples. The Baseline data of each patient was collected with demographic information, laboratory data, disease activity according to the Birmingham Vasculitis Activity Score (BVAS) 2003, disease severity, and imaging data. Results: We were able to examine 91 AAV patients (52 MPA patients and 39 GPA patients) with 82.4% for MPO-ANCA positive and 20.9% for PR3-ANCA positive. Almost half of the patients was female (56.0%). The median age was 70 years [interquartile range (IQR): 64-77]. The median BVAS was 17 (IQR: 12-23). We identified autoantigen of EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1) in 43 of MPA (82.6%) and 16 of GPA (41.0%) at baseline. After 6 months of treatment, no cases of EFEMP1 were identified in MPA and GPA. The clinical features of EFEMP1 positive in AAV patients were higher age at onset (p &lt;0.01), less ear, nose and throat symptoms at initiation of treatment (p &lt;0.05), higher serum Cr at initiation of treatment (p &lt;0.01), higher vasculitis damage index (VDI) renal component at 12 months and 24 months after initiation of treatment (both p &lt;0.05). Conclusion: Our findings indicate that an autoantigen as immune complexes of EFEMP1 were involved in the pathogenesis of AAV patients and may predict renal prognosis. References: [1]Wilde B et.al, Kidney Int. 2011 Mar;79(6):599-612. [2]Falk RJ et.al, J Am Soc Nephrol. 1997 Feb;8(2):314-22. [3]Haas M et.al, Kidney Int. 2004 Jun;65(6):2145-52. Table. Comparison with and without EFEMP1 (all cases) group EFEMP1 positive (n=59) EFEMP1 negative (n=32) **p-value Sex(%male) 27/59 (45.8%) 13/32 (40.6%) 0.665 Age, years 74 (66-78) 68 (60-71) 0.003 WBC(/ml) 8270 (7325-12725) 9150 (7325-11700) 0.280 Cr(mg/dl) 1.4 (0.9-3.8) 0.8 (0.6-1.5) 0.005 CRP(mg/dl) 7.0 (2.3-12.5) 7.6 (4.0-11.0) 0.566 MPA(%) 43/59 (72.9%) 9/32 (28.1%) &lt;0.001 GPA(%) 16/59 (27.1%) 23/32 (71.9%) &lt;0.001 MPO-ANCA positive 54/59 (91.5%) 24/32 (65.6%) 0.003 PR3-ANCA positive* 7/56 (12.5%) 12/32 (37.5%) 0.012 BVAS total 15 (12-20) 20 (12-25) 0.087 BVAS renal positive 53/59 (89.8%) 26/32 (81.3%) 0.332 BVAS chest positive 16/59 (27.1%) 14/32 (43.4%) 0.161 BVAS ENT positive 17/59 (28.8%) 18/32 (56.3%) 0.014 BVAS systemic positive 40/59 (67.8%) 24/32 (75.0%) 0.631 VDI renal 6 months 1 (0-2) 0 (0-1) 0.053 VDI renal 12 months 1 (0-2) 0 (0-1) 0.007 VDI renal 24 months 1 (0-2) 0 (0-1) 0.012 IQR interquartile range. Values are median(IQR) or n(%), *missing data, **Wilcoxon signed-rank test/Fisher’s exact test Disclosure of Interests: Momoko Okamoto: None declared, Kunihiro Ichinose: None declared, Kaname Oyama: None declared, Ken-Ei Sada: None declared, Shin-ya Kaname: None declared, masayoshi harigai Grant/research support from: AbbVie Japan GK, Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Nippon Kayaku Co., Ltd., and Teijin Pharma Ltd. MH has received speaker’s fee from AbbVie Japan GK, Ayumi Pharmaceutical Co., Boehringer Ingelheim Japan, Inc., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kissei Pharmaceutical Co., Ltd., Oxford Immuotec, Pfizer Japan Inc., and Teijin Pharma Ltd. MH is a consultant for AbbVie, Boehringer-ingelheim, Kissei Pharmaceutical Co., Ltd. and Teijin Pharma., Atsushi Kawakami: None declared