Abstract

Background: Achievement of deep remission (DR), defined as a urine protein creatinine ratio (UPCR) ≤0.15 g/gCr with stabilisation of serum creatinine levels, within 12 months after induction therapy is more favourable target than complete renal response (CR), defined as UPCR ≤0.5 g/gCr, to prevent renal flares and damage accrual in patients with active lupus nephritis [1]. However, immunological characteristics of this population have not been elucidated and need to be clarified. Objectives: To elucidate the characteristics of peripheral blood immune cells associated with DR in active lupus nephritis. Methods: We enrolled consecutive patients who underwent induction or re-induction therapies for active lupus nephritis and prospectively assessed peripheral blood immunophenotyping with flowcytometry before and 12 months after starting induction therapies. We compared subpopulations of immunophenotyping between patients with DR, those with CR, and those with non-CR. Results: Fifty two patients were included in the analysis. Median age was 39 years, and 45 (86.5%) were female. Median disease duration was 4.5 years, and SLEDAI was 20. All patients were treated with prednisolone with the median starting dose of 50 mg/day, and 51 (96.2%) patients used immunosuppressants concomitantly. Based on UPCR at 12 months, 28 (54%), 16 (31%), and 8 (15%) were categorised as DR, CR, and non-CR, respectively. Baseline clinical characteristics except for age and disease duration were not different between the DR, CR and non-CR groups. Before induction therapy, the DR group had significantly higher proportions of HLA-DR+CD8+T cells, NKT-like cells, CD19+ B cells, plasmacytoid dendritic cells and CD16+ monocytes (p=0.036, p=0.037, p=0.017, p=0.010, p=0.048, respectively) and had lower proportions of Tfh, CD16- monocytes and basophils compared to the CR group (p=0.021, p=0.038 and p=0.022, respectively) (Figure 1). The DR group also had higher proportions of HLA-DR+ CD8+ T cells and CD19+ B cells and had lower proportions of basophils compared to the non-CR group (p=0.014, p=0.004 and p=0.035, respectively). Only in the DR group, the proportions of plasmablasts, plasma cells and CD16+ monocytes significantly decreased (p=0.005, p=0.002 and p=0.049, respectively), and those of CD8+ T cells, NKT-like cells, CD16- monocytes and basophils increased (p=0.002, p<0.001, p=0.027 and p<0.001, respectively) after induction therapy. At 12 months of treatment, the DR group had lower proportions of Th17, Tfh and plasma cells and higher proportions of NKT-like cells than the CR group. (p=0.041, p=0.005, p=0.012 and p=0.014, respectively). Conclusion: Achievement of DR within 12 months after induction therapies in patients with lupus nephritis is characterised by a multifactorial involvement of peripheral immune cells, including higher proportions of CD19+ B cells and CD16+ monocytes before treatment, persistently lower proportions of Tfh and persistently higher proportions of NKT-like cells, and a decrease in plasma cells and an increases in basophils after treatment. REFERENCES: [1] Kikuchi J, Hanaoka H, Saito S, Oshige T, Hiramoto K, Takeuchi T, Kaneko Y. Deep remission within 12 months prevents renal flare and damage accrual in lupus nephritis. Clin Exp Rheumatol. 2023 Jul;41(7):1500-1506. Acknowledgements: NIL. Disclosure of Interests: Jun Kikuchi: None declared, Hironari Hanaoka: None declared, Shuntaro Saito: None declared, Kazuoto Hiramoto: None declared, Noriyasu Seki Mitsubishi Tanabe Pharma Corporation, Hideto Tsujimoto Mitsubishi Tanabe Pharma Corporation, Tsutomu Takeuchi: None declared, Yuko Kaneko: None declared.