Abstract: SA-PO626
Decreased Monocyte Costimulatory Molecule CD86 Expression in Focal Segmental Glomerulosclerosis Predicts Early Relapse Following Rituximab Therapy
Session Information
- Glomerular Diseases: Immunology, Inflammation - II
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1202 Glomerular Diseases: Immunology and Inflammation
Authors
- Chan, Chang-Yien, National University of Singapore, Singapore, Singapore
- Teo, Sharon, KTP-NUCMI, NUHS, Singapore, Singapore
- Liu, Isaac, National University of Singapore, Singapore, Singapore
- Lam, Kong Peng, Bioprocessing Technology Institute, A*STAR, Singapore, Singapore
- Ng, Kar Hui, National University of Singapore, Singapore, Singapore
- Yap, Hui Kim, National University of Singapore, Singapore, Singapore
Background
We recently reported a subgroup of focal segmental glomerulosclerosis (FSGS) patients bearing an immunological signature of T-cell hyporesponsiveness who responded to rituximab treatment. This study aimed to characterize the immunological subsets in FSGS patients who responded to treatment in order to predict early relapse within the first year following rituximab therapy.
Methods
A total of 29 FSGS patients (median age 14.7 years, range 6.1-25.0 years) receiving rituximab were recruited in this study. Rituximab was administered to patients at a dose of 375 mg/m2 fortnightly to a maximum of 4 doses, and followed up longitudinally. Immunological subsets were monitored at baseline, and 6 months post-rituximab. Statistical analyses was done using Mann-Whitney U test and Wilcoxon signed rank test for paired analysis prior and 6-months post-rituximab. Receiver-operating characteristic (ROC) curve analysis was used to determine predictive utility of the subset for early relapse.
Results
51.7% (15/29) responded to rituximab therapy with characteristic significant downregulation of IFNγ (P<0.01) following PMA/ionomycin stimulation. Of the 15 FSGS patients who responded to treatment, 60% (9/15) had no relapses within the first year post-rituximab (Group I), while 40% (6/15) relapsed (Group II) with comparable median B-cell recovery of 6.0 months and 5.0 months respectively (P=0.41). Patients in Group II had significant lower percent CD86 (75.5±7.0%) on monocytes compared with Group I (91.8±2.5%) (P=0.03). ROC analysis showed that monocyte expression of CD86 (AUC 0.88, 95% CI 0.67-1.00) fared well as a good predictor for relapse (sensitivity 80.0%, specificity 87.5%, PPV 80.0%, NPV 87.5%, with discriminatory threshold <90.2%). CD86 expression in Group II was significantly upregulated 6-months post-rituximab treatment (91.6±2.1%), (P=0.04).
Conclusion
We identified a distinct immunological subset of FSGS patients with decreased monocyte CD86 (B7-2) expression at baseline, who are likely to relapse within a year post-rituximab therapy and hence could benefit from early re-treatment with rituximab. CD86 is a receptor which provides costimulatory signal to T-cell activation, deciding between T-cell fate of immunity or anergy. The role of monocytes in FSGS however remains to be elucidated.
Funding
- Government Support - Non-U.S.