Journal Article

POS1115 LOWER CD169 EXPRESSION ON MONOCYTES IN URINE THAN ON MONOCYTES IN PERIPHERAL BLOOD INDICATES SEVERITY OF RENAL INVOLVEMENT IN SLE PATIENT

Schmiedeberg, K., Bürgi, J., Rubbert-Roth, A., Von Kempis, J., Böni, L., Attar, A. A.

2024

Overview

Background:Systemic lupus erythematosus (SLE) may potentially affect different organs with kidney involvement representing the most significant organ manifestation. There is a need for biomarkers indicating active disease and an early detection of renal disease. Expression of CD169 (SIGLEC1) on peripheral blood monocytes has been proposed as a surrogate for a dominant type I IFN signature and increased disease activity1.Objectives:To study CD169 expression on urine and peripheral blood monocytes in correlation to clinical characteristics and serological markers of disease activity.Methods:64 patients from the St. Gallen SLE cohort, also enrolled in the Swiss SLE Cohort Study (SSCS), were consecutively recruited into this prospective cross-sectional, observational study and compared to 14 age- (39 [32-49] years) and sex (female 12/14 (86%)) matched healthy controls (HC). Expression of CD169 on urine and peripheral blood monocytes was assessed using quantitative flow cytometry.2 Clinical assessment included SELENA-SLEDAI, PGA, SF-36, SLICC/ACR damage index and laboratory parameters as shown in Table 1.Independent associations of continuous and categorical variables were analysed by of variance (ANOVA) models, using the general linear model approach. Correlation analyses were performed calculating parametric Spearman correlation coefficients.Results:37.5% of SLE patients had active disease with a SELENA-SLEDAI ≥4 and 14/64 (22%) of SLE patients had biopsy proven lupus nephritis class III-V. Expression of CD169 on peripheral blood monocytes in SLE patients was significantly higher compared to age and sex matched HC (p = 0.0016) while it was significantly lower on urine monocytes (Figure 1A). In SLE patients, CD 169 expression on peripheral blood monocytes positively correlated with disease activity (SELENA-SLEDAI) (r = 0.384, p = 0.002) (Figure 1B), ESR (r = 0.341, p = 0.006), and anti-dsDNA antibodies levels (r = 0.513, p < 0.0001), while an inverse correlation was observed with C3c (r = - 0.290, p = 0.021) and C4 (r = - 0.258, p = 0.04) levels. Moreover, biopsy proven renal manifestation (r = 0.419, p = 0.001), fever (r = 0.551, p < 0.0001), rash (r = 0.322, p = 0.01), and leucopenia (r = 0.334, p = 0.007) were associated with expression of CD169 on blood monocytes.Baseline characteristics of patients with and without renal disease are detailed in Table 1. CD169 expression on urine monocytes was comparable when analyzing spot-, 12-hour (h)-, and 24-h urine samples. A decreased CD169 expression on urine monocytes (<20%) was detected in 67% of SLE patients, in all patients with biopsy proven nephritis, and in 38% of HC (p = 0.0006). A lower CD169 expression on urine monocytes was associated with an increase in SELENA-SLEDAI (r = 0.280, p = 0.026), with biopsy proven renal manifestation (r = 0.262, p = 0.038) (Figure 1C), an increased albumin/creatinine ratio (r = 0,351 p = 0.005) (Figure 1D) and with serum creatinine levels (r = -0.331, p = 0.008), the presence of anti-Sm- (r = 0,457, p < 0.0001) and levels of anti-dsDNA- (r = 0,290, p = 0.021) antibodies (Table 1).Conclusion:In this cohort of SLE patients, higher expression of CD169 on peripheral blood monocytes inversely correlated with decreased CD169 expression on monocytes in urine (r = 0.336, p = 0.007), and was associated with the presence of renal disease and markers of active renal SLE disease. Our data suggest that lower CD169 expression on monocytes in urine than on monocytes in peripheral blood indicates more severe renal involvement and should be explored in more detail.REFERENCES:[1] Biesen R, et al. Arthritis Rheum 2008;58(4):1136-45[2] Stuckrad SLV, et al. Lupus 2020;29(14):1914-25Acknowledgements:We would like to thank the lupus volunteers of the Swiss SLE Cohort Study St.Gallen who made this work possible.Disclosure of Interests:None declared.

• Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism,Elsevier Limited
• Subject: Anti-DNA antibodies / Biomarkers / Biopsy / Cohort analysis / Correlation analysis / Creatinine / Flow cytometry / Kidney diseases / Leukopenia / Lupus / Lupus nephritis / Monocytes / Observational studies/registry / Peripheral blood / Scientific Abstracts / Systemic lupus erythematosus / Urine