Urine Complement Ba Levels During Flares of Renal Disease in Patients with ANCA-Associated Vasculitis

Salem Almaani¹, Christopher Toy ², Anna Levesque ², Lynn Fussner ¹, Alexa Meara ¹, Lianbo Yu ¹, David Cuthbertson ³, Simon Carette ⁴, Nader A. Khalidi ⁵, Curry L. Koening ⁶, Carol Langford ⁷, Carol A. McAlear ⁸, Larry Moreland ⁹, Christian Pagnoux ¹⁰, Philip Seo ¹¹, Antoine Sreih ¹², Steven Ytterberg ¹³, Paul Monach ¹⁴, Peter Merkel ¹², Brad Rovin ¹ and Dan Birmingham ¹⁵, ¹The Ohio State University Medical Center, Columbus, OH, ²Ohio State University, Columbus, OH, ³University of South Florida, Tampa, FL, ⁴Division of Rheumatology, Mount Sinai Hospital, University of Toronto, Toronto, Canada, ⁵McMaster University, Hamilton, ON, Canada, ⁶University of Utah Hospital, Salt Lake City, UT, ⁷Cleveland Clinic, Cleveland, OH, ⁸University of Pennsylvania - VCRC Project Manager, Philadelphia, PA, ⁹University of Pittsburgh, PITTSBURGH, PA, ¹⁰Mount Sinai Hospital and University Health Network, Toronto, ON, Canada, ¹¹Johns Hopkins Medicine, Baltimore, MD, ¹²University of Pennsylvania, Philadelphia, PA, ¹³Mayo Clinic College of Medicine, Rochester, MN, ¹⁴Brigham and Women's Hospital, Boston, MA, ¹⁵The Ohio State University Medical Center, Columbus

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: ANCA, Biomarkers, Kidney and complement

Session Information

Date: Tuesday, November 12, 2019

Title: Vasculitis – ANCA-Associated Poster I

Session Type: Poster Session (Tuesday)

Session Time: 9:00AM-11:00AM

Background/Purpose: The alternative complement pathway has been implicated in the pathogenesis of ANCA-associated vasculitis (AAV). Change in markers of complement activation within patients have not been reported. This study measured levels of urinary complement fragment Ba (uBa) longitudinally in patients with AAV.

Methods: Urine levels of uBa were measured by ELISA (corrected to urine creatinine) in 3-4 serial samples in 60 patients with AAV: 20 who developed a flare with renal disease (ReF), 20 who developed a non-ReF (NReF), and 20 in long term remission (LTR). Because timing of pre-flare to flare visits differed from patient to patient, these values were averaged for each patient (pre-ReF or pre-NReF), normalized by natural log-transformation, and compared to flare by paired t test. Differences between ReF and NReF levels were assessed by unpaired t test. Differences between pre-ReF, pre-NReF, and average LTR levels were assessed by ANOVA.

Results: The median age of participants was 59 years, 53% were male, 93% were White, and 93% were ANCA positive. There were no differences in uBa levels between pre-ReF, pre-NReF, and LTR (P=0.360) (Figure). Despite overlap, overall uBa levels were higher in ReF compared to pre-ReF (P=0.017), and to NReF (P = 0.002). Levels of uBa levels did not change from pre-NReF to NReF (P=0.232).

Conclusion: Increased uBa levels suggests that alternative complement pathway activation contributes to the pathogenesis of ReF in AAV. However, many patients experiencing ReF do not show high uBa levels. Thus, uBa may identify a subset of patients with ReF who might benefit from complement-targeted therapies. Other factors defining this subset remain to be determined.

Figure 1: Urine Ba levels in patients with ANCA-Associated vasculitis. Pre-ReF: mean level before renal flare. ReF: level at renal flare. Pre-NReF: mean level before non-renal flare. NReF: level at non-renal flare. LTR: mean level with long-term remission.

Figure 2: Figure 1: Urine Ba levels in patients with ANCA-Associated vasculitis. Pre-ReF: mean level before renal flare. ReF: level at renal flare. p-value Renal Flare -remission vs. flare 0.017-. p-value Flare -Renal flare vs Non-renal flare=0.002-

Figure 3: Change in urine Ba levels in individual patients before and at flare.

Disclosure: S. Almaani, None; C. Toy, None; A. Levesque, None; L. Fussner, None; A. Meara, None; L. Yu, None; D. Cuthbertson, None; S. Carette, None; N. Khalidi, None; C. Koening, None; C. Langford, Bristol-Myers Squibb, 2, GlaxoSmithKline,, 2, ChemoCentryx, 2, Genentech, 2, Bristol-Myers Squibb, 5, 9, Abbvie, 9, AstraZeneca, 9; C. McAlear, None; L. Moreland, None; C. Pagnoux, ChemoCentryx, 5, Chemocentryx, 5, Genetech/Roche, 5, Genzyme/Sanofi, 5, GlaxoSmithKline, 5, Hoffman-La Roche, 2, 5, 8, Hoffman-LaRoche, 2, 5, 8, Sanofi, 5; P. Seo, None; A. Sreih, Bristol-Meyers Squibb, 3, Bristol-Myers Squibb, 3; S. Ytterberg, None; P. Monach, Kiniska, 5, Insmed, 5, Celgene, 5, ChemoCentryx, 5, Medscape, 8, NACCME, 8; P. Merkel, Abbvie, 5, AbbVie, 5, AstraZeneca, 2, 5, AstraZeneca,, 2, 5, Biogen, 5, Boeringher-Ingelheim, 2, 5, Bristol-Myers Squibb, 2, 5, Celegene, 2, 5, Celgene, 2, 5, ChemoCentryx, 2, 5, CSL Behring, 5, Genentech/Roche, 2, 5, Genetech/Roche, 2, 5, Genzyme/Sanofi, 2, 5, GlaxoSmithKline, 2, 5, InflaRx, 5, Insmed, 5, Jannsen, 5, Kiniksa, 5, Kypha, 2, TerumoBCT, 2, UpToDate, 7; B. Rovin, Genentech, Inc., 9, Admirx, 5, Alexion, 5, Aurinia, 5, Biogen, 5, Biomarin, 5, Bristol Myers Squibb, 5, Callidates, 5, ChemoCentryx, 2, 5, Chugai Pharmaceuticals, 5, EMD Serono, 2, 5, Genentech, 5, Janssen, 5, Lupus Foundation of America, 5, Mallinckrodt, 5, MedImmune, 5, Morphosys, 5, Novartis, 5, Omeros, 3, Pfizer, 5, Ra Pharmaceuticals, 5, Retrophin, 2, 5, Rigel, 2, 5, Takeda, 5, AstraZeneca, 2, Hoffman-La Roche, 2, Human Genome Sciences Inc., a GSK Company, 2, NIH/NIDDK, 2, RILITE Foundation, 2; D. Birmingham, None.

To cite this abstract in AMA style:

Almaani S, Toy C, Levesque A, Fussner L, Meara A, Yu L, Cuthbertson D, Carette S, Khalidi N, Koening C, Langford C, McAlear C, Moreland L, Pagnoux C, Seo P, Sreih A, Ytterberg S, Monach P, Merkel P, Rovin B, Birmingham D. Urine Complement Ba Levels During Flares of Renal Disease in Patients with ANCA-Associated Vasculitis [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/urine-complement-ba-levels-during-flares-of-renal-disease-in-patients-with-anca-associated-vasculitis/. Accessed .

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