Deep Remission During Induction Therapy for Lupus Nephritis Prevents Damage Accrual and Associates with the Baseline Proportions of Peripheral Treg, CD8+ T Cells, and NKT-like Cells

Jun Kikuchi¹, Hironari Hanaoka ¹, Shuntaro Saito ¹, Tatsuhiro Oshige ¹, Kazuoto Hiramoto ¹, Yuko Kaneko ¹, Noriyasu Seki ², Hideto Tsujimoto ² and Tsutomu Takeuchi ¹, ¹Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan, ²Mitsubishi Tanabe Pharma Corporation Sohyaku. Innovative Research Division, Toda-shi, Saitama, Japan

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: Lupus nephritis, remission, Systemic lupus erythematosus (SLE), T cells and B cells

Session Information

Date: Tuesday, November 12, 2019

Title: SLE – Clinical Poster III: Treatment

Session Type: Poster Session (Tuesday)

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

Background/Purpose: chievement of renal remission has been the target of the induction therapy in patients with active lupus nephritis (LN). Deep remission (DR) defined as the reduction of urine protein Cr ratio (UPCR) to 0.15 g/gCr was reported to reduce renal flare. However, the utility and associated factors of DR are not clearly evaluated enough. We herein evaluated the characteristics of the patients with DR.

Methods: We enrolled the patients with active LN who started induction therapy from February 2015 to February 2018 in our hospital and were followed for more than 12 months. We prospectively assessed the achievement of complete renal response (CR), defined as stabilization (within 25%) in serum Cr with reduction of UPCR to 0.5 g/gCr, and DR. Standardized peripheral immunophenotyping by flowcytometry was analyzed with whole blood samples from all patients before starting induction therapy. Finally, we assessed a renal flare and the progression of damage accrual with SLICC-damage index (SDI) and the associations with achievement of DR.

Results: Forty-one patients were enrolled. Mean initial dose of prednisolone was 0.89 ± 0.24 mg/kg/day with 39.0% of intravenous cyclophosphamide, 41.5% of mycophenolate mofetil, and 17.1% of tacrolimus. Mean observational period was 31.3 ± 11.3 months. CR was achieved in 31 (75.6%) patients within 6 months and 33 (80.5%) within 12 months after starting induction therapy. DR was achieved in 15 (36.6%) and 22 (53.7%) within 6 and 12 months, respectively. Five (12.2%) patients had renal proteinuric flare, and no patient achieving DR had experienced it during observational periods. Increase in SDI was observed in 17.1% of patients. Especially, DR within 12 months was significantly associated with no progression of SDI (p=0.022). In addition, UPCR at final visit was significantly lower in patients with DR (p< 0.001). Patients with DR within 12 months had a higher titer of SLEDAI score (p=0.033) and higher prevalence of co-existing musculoskeletal manifestation (p< 0.001) at baseline. The proportions of HLA-DR⁺ Treg (CD3⁺CD4⁺CD25⁺CD127^low) and naïve CD8⁺ T cells (CD3⁺CD8⁺CD45RA⁺CCR7⁺) were lower and the proportions of CD19⁺ B cells, HLA-DR⁺ CD8⁺ T cells, effector CD8⁺ T cells (CD3⁺CD8⁺CD45RA⁺CCR7^–), and NKT-like cells (CD3⁺CD19^–CD56⁺γδTCR^–) were significantly higher in patients with DR than those without.

Conclusion: Achievement of DR within 12 months after induction therapy was associated with reduction in damage accrual in patients with active LN, which indicated DR can be a selected target of the treatment. Higher disease activity score and the proportions of peripheral Treg, CD8⁺ T cells, and NKT-like cells at baseline might be surrogate markers for achievement of DR.

Table1

Table1. Clinical characteristics associated with achievement of deep remission within 12 months after starting induction therapy.

Figure 1. The significantly different proportions of peripheral immune cells between the patients achieving deep remission during 12 months after induction therapy and those without. Cut-off for significance was p-value <0.05 -Wilcoxon’s test-.

Disclosure: J. Kikuchi, Mitsubishi Tanabe Pharma Corporation Sohyaku, 2; H. Hanaoka, Mitsubishi Tanabe Pharma Corporation Sohyaku, 2; S. Saito, Mitsubishi Tanabe Pharma Corporation Sohyaku, 2; T. Oshige, Mitsubishi Tanabe Pharma Corporation Sohyaku, 2; K. Hiramoto, Mitsubishi Tanabe Pharma Corporation Sohyaku, 2; Y. Kaneko, Mitsubishi Tanabe Pharma Corporation Sohyaku, 2; N. Seki, Mitsubishi Tanabe Pharma Corporation, 3; H. Tsujimoto, Mitsubishi Tanabe Pharma Corporation, 3; T. Takeuchi, Mitsubishi Tanabe Pharma Co., 2, 8, Mitsubishi Tanabe Pharma Corporation, 2, 5, 8.

To cite this abstract in AMA style:

Kikuchi J, Hanaoka H, Saito S, Oshige T, Hiramoto K, Kaneko Y, Seki N, Tsujimoto H, Takeuchi T. Deep Remission During Induction Therapy for Lupus Nephritis Prevents Damage Accrual and Associates with the Baseline Proportions of Peripheral Treg, CD8+ T Cells, and NKT-like Cells [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/deep-remission-during-induction-therapy-for-lupus-nephritis-prevents-damage-accrual-and-associates-with-the-baseline-proportions-of-peripheral-treg-cd8-t-cells-and-nkt-like-cells/. Accessed .

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