AB1049 BAFF-MRNA EXPRESSION IN PERIPHERAL BLOOD VERSUS RENAL TISSUE IN ACTIVE PROLIFERATIVE LUPUS NEPHRITIS
Authors: A. Beltagy, R. S. Z. Taleb, M. Allam, R. Mahmoud, A. El-Girby, A. Abdelati
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Systemic Lupus Erythematosus (SLE) is an auto-immune disease that affects multiple systems in the body. Up to half of SLE patients develop Lupus Nephritis, which is classified into six classes, with classes III and IV being the most proliferative. Lupus Nephritis (LN) severity and prognosis are influenced by clinical and laboratory biomarkers. B-cell activating factor (BAFF) plays a fundamental role in pathogenesis of SLE. Belimumab, an immunoglobulin G targeting BAFF, is FDA-approved for treating active, autoantibody-positive adult SLE. Recent studies show increased efficacy when adding belimumab to standard therapy for managing LN. Although there is great difficulty in finding reliable markers for stratifying patients and predicting prognosis, BAFF is still under investigation as a potential biomarker. <sup>[1]</sup> <h3>Objectives:</h3> The objectives of the study were to assess the difference in baseline peripheral and renal tissue BAFF expression in active proliferative (pLN), and the correlation with different baseline and response assessment parameters. <h3>Methods:</h3> Patients diagnosed with active pLN were recruited from Alexandria Main University Hospital lupus clinic and followed for 6 months after start of standard induction protocol with pulse corticosteroid therapy followed by either mycophenolate mofetil (MMF), or IV euro-lupus cyclophosphamide (followed by either MMF or azathioprine). At baseline, patients were assessed clinically and by testing for routine lab parameters as well as urinary protein creatinine ratio (uPCR), serologic markers, and activity markers (SLEDAI-2K and rSLEDAI), obtaining renal biopsy for classification and activity versus chronicity evaluation, Measuring peripheral mononuclear cell (pMNC) BAFF expression and intrarenal BAFF expression using RT quantitative PCR was done at baseline only. After 6 months of the start of treatment, the same parameters were reassessed. Renal response was defined as "the reduction of u-PCR by 50% or more and a normal or nearly-normal GFR (or, if previously abnormal, within 10% of the range of normal GFR. <sup>[2]</sup> <h3>Results:</h3> The study included 15 patients with early active pLN: median age = 24 years (range 17-42), 13 females, 7 class III ± V, 8 class IV ± V, 9 responders (R) versus 6 non-responders (NR), median activity index = 9 (range: 4-13), median chronicity index 3 (range 0-8). At baseline, median renal BAFF-mRNA expression was higher than peripheral pMNC expression, but it was statistically non-significant (p= 0.97) pMNC BAFF-mRNA was only positively correlated with age at the onset of LN (r= 0.534, p= 0.04) and negatively correlated to serum albumin level (r= -0.725, p=0.012) while renal BAFF-mRNA was only strongly correlated with the increase in uric acid level (r= 0.782, p=0.013). Both studied parameters did not correlate with baseline serological measures, SLEDAI, rSLEDAI or histopathological parameters. Both baseline median intrarenal and pMNC BAFF-mRNA were higher in patients who showed an early 6-month reduction in proteinuria &gt;50% (responders), however, the difference in intrarenal BAFF-mRNA was more pronounced (Figure 1). Lower intrarenal BAFF-mRNA correlated better than pMNC expression with a reduction in uPCR and reduction in creatinine after 6 months (Figure 2) <h3>Conclusion:</h3> The study result indicate that renal tissue BAFF expression is superior to peripheral expression in the representation of activity and prognosis of LN, however, these results were not statistically significant. <h3>REFERENCES:</h3> [1] Tektonidou et al. Risk of End-Stage Renal Disease in Patients With Lupus Nephritis, 1971-2015: A Systematic Review and Bayesian Meta-Analysis. Arthritis &amp; rheumatology. 2016. [2] Rovin BH, et al. Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular Diseases. Kidney Int. 2020 <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>