TY - JOUR T1 - Constitutive reduction in the checkpoint inhibitor, CTLA-4, does not accelerate SLE in NZM 2328 mice JF - Lupus Science & Medicine DO - 10.1136/lupus-2018-000313 VL - 6 IS - 1 SP - e000313 AU - William Stohl AU - Ning Yu AU - Samantha A Chalmers AU - Chaim Putterman AU - Chaim O Jacob Y1 - 2019/02/01 UR - http://lupus.bmj.com/content/6/1/e000313.abstract N2 - Background/objective Treatment with immune checkpoint inhibitors (ICIs) in oncology patients is increasing. Although ICIs trigger rheumatic immune-related adverse events, development of SLE features has been rare. Whether long-term treatment with ICIs would promote SLE features remains unknown. To begin to address this, we generated SLE-prone NZM 2328 mice with lifelong reduction in CTLA-4 expression.Methods Since CTLA-4-deficient (Ctla4− /−) NZM mice developed a lethal lymphoproliferative disorder by 3–6 weeks of age, development of SLE in these mice could not be studied. Ctla4 haploinsufficient NZM.Ctla4+ / − mice were assessed in parallel with littermate female NZM.Ctla4+ / + mice. Evaluations included CTLA-4 expression and lymphocyte profiles, assessed by fluorescence-activated cell sorting; serological profiles, assessed by ELISA; renal immunopathology, assessed by histology and immunofluorescence; and clinical courses, assessed by mortality.Results CTLA-4 expression was lower in NZM.Ctla4+ / − mice than in NZM.Ctla4+ / + mice. Spleen mononuclear cells, B cells, plasma cells, CD4+ cells, recently activated CD4+ cells and CD4+ T regulatory (Treg) cells were increased in NZM.Ctla4+ / − mice (p≤0.042). The serological profile, degree of renal immunopathology and mortality in NZM.Ctla4+ / − mice remained unaffected.Conclusion Lifelong reduction in CTLA-4 expression in NZM mice neither accelerated nor aggravated SLE. Expansion in Treg cells may have played a protective role. Our observations raise the hope that long-term treatment of patients with SLE with an anti-CTLA-4 agent, should the need arise, would not adversely affect SLE disease activity. ER -