ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1493

Association of the Soluble Terminal Complement Complex C5b-9 (sC5b-9) with Urinary Signs of Kidney Disease in a Swiss SLE Cohort

Kristin Schmiedeberg1, Ruediger B. Mueller2, Thomas Neumann3, Ian Pirker1, Philipp Rein4, Camillo Ribi5, Andrea Rubbert-Roth6, Michael Kirschfink7, Jutta Schroeder-Braunstein7, Reinhard Voll8 and Johannes von Kempis1, 1Kantonsspital St. Gallen, St.Gallen, Switzerland, 2Clinic of Rheumatology, Medical University Hospital Aarau, Aarau, Switzerland, 3Kantonsspital St.Gallen, St.Gallen, Switzerland, 4Landeskrankenhaus Hohenems, Wolfurt, Austria, 5CHUV, Lausanne, Switzerland, 6Kantonspital St Gallen, St.Gallen, Switzerland, 7Universitätsklinikum Heidelberg, Heidelberg, Germany, 8Department of Rheumatology and Clinical Immunology, University Medical Center, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Freiburg, Germany

Meeting: ACR Convergence 2021

Keywords: , , ,

Session Information

Date: Tuesday, November 9, 2021

Title: SLE – Etiology & Pathogenesis Poster (1480–1506)

Session Type: Poster Session D

Session Time: 8:30AM-10:30AM

Background/Purpose: Few reliable laboratory biomarkers exist to determine disease activity in SLE. The role of the soluble terminal complement complex, sC5b-9, in active SLE has yet to be elucidated. Its proinflammatory effects on a number of cell types, e.g. glomerular mesangial cells, have been reported.

The objective of the study was to correlate clinical activity according to the components of the SLEDAI and PROs with levels of soluble complement proteins and laboratory parameters of standard care. In completion of the preliminary analyses based on 2 consecutive patients’ visits that suggested an association of sC5b-9 with haematuria und glomerular dysmorphic erythrocytes1, we here present the analysis of all 4 visits during the 2-year time period of the study of 127 patients.

Methods:
Study population and design:
Patients fulfilling the ACR criteria were included into the Swiss SLE Cohort Study (SSCS, from the St. Gallen Centre) and were entered consecutively into a prospective observational, cross-sectional study (Oct. 2015 – Jan. 2021). The following parameters were determined at 2-4 clinical visits, at least 6 months apart, and compared with 48 healthy controls (age- and gender-matched):

  • clinical disease activity (SELENA-SLEDAI, PGA), PROs (FACIT, SF-36) and SLICC-Damage
  • sC5b-9 by ELISA
  • a spectrum of routine laboratory of standard care

Statistics:
Independent associations of continuous variables were studied by analysis of covariance (ANCOVA) models, using the general linear model approach. Correlation analyses were performed calculating nonparametric Spearman rank correlation coefficients.

Results: Disease activity in our cross-sectional cohort was generally low (SELENA-SLEDAI 1.7 ± 2.6 (mean ± SD), SLEDAI of > 4 in 8.5% patients, 8.1 ± 3.3 (mean ± SD)). The median age was 48 [interquartile range (IQR) 38–54] years and disease duration 5.3 [IQR 3.8-8.8] years, respectively. Clinical manifestations were mainly hematologic 59%, musculoskeletal 56%, skin 41%, photosensitivity 41%, oral ulcers 37% and renal 15%.

A significant association in line with urinary signs of renal manifestations was found between:

  • haematuria (F=2.501, p< 0.0001) and/or increase in glomerular dysmorphic erythrocytes
  • (F=1.593, p= 0.039) and sC5b-9
  • A significant correlation of proteinuria, albuminuria or pyuria with sC5b-9 could not be detected.

There were further correlations between sC5b-9 and:

  • dsDNA antibodies (ab) (r=0.119, p= 0.014), IgG (r=0.181, p< 0.0001), soluble IL-2 receptor (r=0.100, p= 0.042), ESR (r=0.112, p= 0.017), CRP (r=0.223 p< 0.0001), C3a (r=0.317, p< 0.0001), C3 (r= 0.224, p< 0.0001)
  • In addition, IgG (F=2.420, p= 0.004) and sIL-2 receptor (F=8.756, p< 0.0001) levels were associated with SELENA-SLEDAI in a multivariate model after adjustment for age, gender, CRP, ESR, levels of dsDNA ab, C3 and C4.

Conclusion: The study showed that sC5b-9 was associated with laboratory parameters of standard care and elevated in our cohort in line with urinary signs of renal manifestation. It may contribute to the pathogenesis of renal glomerular manifestation in SLE and serve as a new marker of active renal disease.

References:
1. Arthritis Rheumatol. 2019; 71 (suppl 10) 1176-1178.

Disclosures: K. Schmiedeberg, None; R. Mueller, None; T. Neumann, None; I. Pirker, None; P. Rein, None; C. Ribi, None; A. Rubbert-Roth, AbbVie, 2, 6, Bristol-Myers Squibb, 2, 6, Chugai, 2, 6, Roche, 2, 6, Gilead, 2, 6, Janssen, 2, 6, Eli Lilly, 2, 6, Sanofi, 2, 6, Amgen, 2, 6, Novartis, 2, 6; M. Kirschfink, None; J. Schroeder-Braunstein, None; R. Voll, None; J. von Kempis, None.

To cite this abstract in AMA style:

Schmiedeberg K, Mueller R, Neumann T, Pirker I, Rein P, Ribi C, Rubbert-Roth A, Kirschfink M, Schroeder-Braunstein J, Voll R, von Kempis J. Association of the Soluble Terminal Complement Complex C5b-9 (sC5b-9) with Urinary Signs of Kidney Disease in a Swiss SLE Cohort [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/association-of-the-soluble-terminal-complement-complex-c5b-9-sc5b-9-with-urinary-signs-of-kidney-disease-in-a-swiss-sle-cohort/. Accessed .

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