Use of rituximab in idiopathic retroperitoneal fibrosis

Background Retroperitoneal fibrosis (RPF) is characterized by the proliferation of fibrous tissue in the retroperitoneum. The majority of RPF cases are due to idiopathic or IgG4-related disease. Recent studies on IgG4-related disease have shown rituximab to be an effective treatment. The current first-line treatment for idiopathic RPF (iRPF) is glucocorticoid therapy. Relapse rates vary widely in the literature, and DMARDs remain poorly studied. We sought to evaluate the efficacy of rituximab in idiopathic RPF by quantifying changes in iRPF diameter on imaging pre- and post-rituximab therapy and response by lab parameters in 10 iRPF patients. Methods We selected 10 patients diagnosed with iRPF and previously treated with rituximab (1000 mg) in two doses approximately 2 weeks apart. Pre- and post-therapy contrast enhanced cross-sectional abdomen and pelvis imaging were compared. In all patients, the thickest portion of the peri-aortic disease was measured in the axial and coronal planes. The presence of acute or long standing back pressure related renal findings were documented. Details of clinical visits including patient demographics and laboratory evaluations were collected pre- and post-therapy. Statistical analysis was performed using a Wilcoxon signed rank test. Results The RPF diameter around the aorta before and after therapy decreased from a mean of 15.9 ± 4.9 mm to 10.6 ± 6.1 mm, respectively (p < 0.01). The craniocaudal iRPF mean length decreased from 108.6 mm ± 40.4 mm to 90.6 mm ± 45.9 mm (p = 0.02). Conclusion A comparison of pre and post-rituximab imaging studies revealed a statistically significant decrease in iRPF diameter following treatment with rituximab.Medicine, Faculty ofNon UBCHematology, Division ofMedicine, Department ofPathology and Laboratory Medicine, Department ofRadiology, Department ofRheumatology, Division ofUrologic Sciences, Department ofReviewedFacult

PD-1-mediated attrition of polyfunctional memory CD8 + T cells in chronic toxoplasma infection

We reported earlier that during chronic toxoplasmosis CD8(+) T cells become functionally exhausted with concomitant PD-1 upregulation, leading to eventual host mortality. However, how immune exhaustion specifically mediates attrition of CD8 polyfunctionality, a hallmark of potent T-cell response, during persistent infections has not been addressed. In this study, we demonstrate that PD-1 is preferentially expressed on polyfunctional memory CD8(+) T cells, which renders them susceptible to apoptosis. In vitro blockade of the PD-1–PD-L1 pathway dramatically reduces apoptosis of polyfunctional and interferon γ(+)/granzyme B(−) memory but not effector CD8(+) T cells. In summary, the present report underscores the critical role of the PD-1–PD-L1 pathway in mediating attrition of this important CD8(+) T-cell subset and addresses the mechanistic basis of how αPD-L1 therapy reinvigorates polyfunctional CD8 response during chronic infections. The conclusions of this study can have profound immunotherapeutic implications in combating recrudescent toxoplasmosis as well other chronic infections