AB0588 Identification of risk factors for herpes virus infections with immunophenotyping during induction therapy in patients with active lupus nephritis
Authors: J. Kikuchi, M. Ushikubo, S. Saito, H. Yasuoka, K. Yamaoka, H. Tsujimoto, K. Sugahara, T. Takeuchi
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Herpes virus infections (HVIs) including cytomegalovirus infections (CMVs) and herpes zoster (HZ) remains as major complications during treatments with immunosuppressant (IS) in patients with autoimmune diseases.<sup>1 2</sup> Previous reports have suggested the associations between virus infections and characteristics of T cells.<sup>3 4</sup> <h3>Objectives</h3> To elucidate the characteristics of peripheral immune cells associated with risk factors of HVIs during induction therapies in patients with active lupus nephritis (LN). <h3>Methods</h3> Standardised peripheral immunophenotyping was performed using flow cytometry in active LN and ANCA-associated vasculitis (AAV) patients starting induction therapy and also with inactive LN patients with maintenance therapy between April 2015 to April 2017. The definition of HVIs was the infection necessary to administer anti-viral agents. <h3>Results</h3> Sixty-two LN patients and 11 AAV patients were enrolled. Among 30 active LN patients, 27 were analysed except for 3 patients (2 died and 1 withdrawn consent). Mean age was 41.7 years, 9 patients (33%) had newly-onset, and mean SLE disease activity index (SLEDAI) was 19.3. All active LN patients were treated with prednisolone (PSL) (mean 51.7 mg/day) and 25 were treated with an additional IS (cyclophosphamide [CYC];13, mycophenolate mofetil;8, tacrolimus;3, rituximab [RTX];1). Six (22.2%) patients developed HVIs (5 CMVs and 1 HZ) within 3 months following induction therapy. None of the 32 LN patients in maintenance phase (mean age, 54.8; SLEDAI, 2.5; PSL 2.5 mg/day) developed HVIs during the mean 2.8 years-observational period. Two (18.2%) AAV patients developed HVIs within 3 months following induction therapy. All AAV patients (mean age, 64.3) were treated with PSL (mean 41.8 mg/day) and 10 with IS (CYC;5, RTX;3, azathioprine;1, methotrexate;1). Among active LN patients, univariate analysis revealed that older age, lower proportions of naïve CD8 +T cells, higher proportions of effector CD8 +T cells and HLA-DR +regulatory T cells (Tregs) at baseline and lower naïve CD8 +T cells at month 3 associated with HVIs (p=0.011, p&lt;0.001, p=0.009, p=0.024, p&lt;0.001 respectively). Unexpectedly, lymphocyte count, IgG titer, usage of CYC at baseline, renal response and change in SLEDAI at month 3 did not associate with HVIs. Multivariate analysis revealed that low proportions of naïve CD8 +T cells and high proportions of HLA-DR +Tregs at baseline were the only detectable independent risk factor for HVIs (p=0.014). Among AAV patients, univariate analysis showed that older age, lower proportions of naïve CD8 +T cells, higher proportions of Tregs at baseline associated with HVIs. However, multivariate analysis showed no independent risk factor for HVIs among them. <h3>Conclusions</h3> Our results suggest that active LN patients with low proportion of naïve CD8 +T cells and high HLA-DR +Tregs at the time of induction therapy should be closely monitored for HVIs. The different results between LN and AAV implicated the different risks of HVIs by immunophenotyping. Larger prospective study is desired to confirm our results. <h3>References</h3> [1] Takizawa Y. et al. Rheumatology (Oxford). 2008;47:1373–8. [2] Chakravarty EF, et al. Lupus. 2013;22:238–44. [3] Weltevrede M, et al. Exp Gerontol. 2016;77:87–95. [4] Egli A, et al. PLoS One. 2012;7:e43937. <h3>Disclosure of Interest</h3> J. Kikuchi: None declared, M. Ushikubo: None declared, S. Saito: None declared, H. Yasuoka: None declared, K. Yamaoka: None declared, H. Tsujimoto Employee of: Mitsubishi Tanabe Pharma Corporation, K. Sugahara Employee of: Mitsubishi Tanabe Pharma Corporation, T. Takeuchi Grant/research support from: Mitsubishi Tanabe Pharma Corporation