Article Figures & Data
Figures
- Figure 1.
Representative immunoblots demonstrate four patterns of response of IgG4 anti-PLA2R signal at sequential time points after rituximab treatment (0 to 30 months; all patients are missing data from one or more time points). Panel A depicts the typical reduction (through 6 months) and disappearance (9 months and beyond) of anti-PLA2R exhibited by most patients. Panel B shows a similar pattern (upper blot), but a longer exposure of the immunoblot (lower) demonstrates that the anti-PLA2R signal persists at a very weak, subthreshold value through the final time point (arrow). Panel C is representative of the six patients in which anti-PLA2R did not substantially decline after treatment. Panel D depicts the single patient whose anti-PLA2R returned with relapse of his disease after having initially disappeared.
- Figure 2.
The clinical response to rituximab is temporally associated with the immunologic response. Representative plots of anti-PLA2R (gray squares) and proteinuria (black diamonds) versus time after initial rituximab treatment. Values are plotted as percent of baseline value for sake of better comparison between subjects. The four graphs correspond to the four immunoblots depicted above and to the following subjects in Table 1: A, subject 13; B, subject 6; C, subject 22; D, subject 9.
- Figure 3.
Anti-PLA2R (left box plot) declines in advance of a more gradual decline of proteinuria (right) in those patients who cleared anti-PLA2R. Boxes represent median (line) and 25th and 75th percentiles, with whiskers to the 10th and 90th percentiles. Outliers are represented by filled circles.
Tables
- Table 1.
Baseline characteristics and responses to treatment with rituximab for all subjects grouped according to baseline anti-PLA2R positivity and clearance versus persistence of anti-PLA2R at 12 months after treatment
Age Gender Disease Duration (Months) Serum Creatinine (mg/dl) Creatinine Clearance (ml/min per 1.73 m2) Baseline Anti-PLA2R 12-Month Anti-PLA2R Baseline Proteinuria (g/d) Outcome (12 Months) Outcome (24 Months) Group 1: anti-PLA2R positive; clearance by 12 months 1 40 M 6 1.0 113 31,328 0 11.8 NR NR 2 60 F 8 1.4 46 28,560 0 8.49 PR CR 3 53 M 6 1.3 75 25,401 0 8.48 CR CR 4 44 M 144 1.6 80 25,360 495e 11.87 NRf PR 5 52 M 6 1.5 74 25,067 0 14.69 NRf PR 6 38 M 40 0.8 156 24,882 610e 8.32 PR PR 7 33 M 5 1.1 109 23,985 0 10.79 CR CR 8 46 M 8 1.3 81 23,761 280e 10.09 PR PR 9 59 M 12 1.1 87 22,462 0 9.88 PR RL 10 30 M 11 2.1 73 22,251 0 12.12 NRf PR 11 51 M 24 2.3 36 21,325 0 16.27 NR PR 12 47 M 12 1.8 49 20,602 0 14.23 NRf PR 13 50 M 12 2.0 46 19,487 0 15.46 PR PR 14 46 M 60 2.1 61 19,062 0 15.77 PR CR 15 29 M 4 1.4 49 18,585 0 13.69 NRf PR 16 57 F 4 0.8 30 13,506 660e 8.59 PR CR 17 64 F 35 1.0 89 9395 0 7.02 PR PR Summary 47 ± 10 14:3 11 1.5 ± 0.5 74 ± 32 22,462a 0b 11.8 Group 2: anti-PLA2R positive; persistence at 12 monthsc 18 42 M 5 1.0 119 31,994 4710 26.46 NRf PR 19 60 M 13 2.6 40 31,425 21,190 20.08 NR ESRD 20 38 M 10 1.8 68 31,082 16,890 23.44 NR ΔIST 21 49 M 37 1.4 79 29,381 6361 8.05 NR ΔIST 22 42 M 17 1.3 83 29,283 20,595 9.88 NR PR 23 63 M 6 1.5 63 27,041 5725 9.09 NR ΔIST 24c 80 M 4 2.0 34 31,091 NAc 9.95 ΔIST ΔIST 25c 45 M 10 1.0 114 21,903 NAc 8.85 PR PR Summary 49 ± 10 6:0 11.5 1.6 ± 0.6 75 ± 26 30,231a 11,625b 14.98 Group 3: anti-PLA2R negative 26 54 M 96 2.30 49 220d 5.73 PR PR 27 52 M 6 1.20 145 0d 7.76 PR PR 28 37 F 10 0.90 102 0 8.4 PR CR 29 53 M 13 1.80 58 0 23.54 Died Died 30 53 M 7 1.80 59 0 16.59 NR ESRD 31 44 F 8 0.70 116 0 6.1 PR CR 32 43 M 108 1.90 59 0 12.76 NR NRf 33 29 M 5 1.00 126 0 11.33 PR CR 34 62 M 7 1.40 67 0 19.16 PR CR 35 42 M 12 1.10 90 0 7.81 PR PR Summary 47 ± 10 8:2 9 1.4 ± 0.5 87 ± 34 0 9.86 Baseline and 12-month anti-PLA2R levels are presented in arbitrary densitometric units. Summary data are presented as means ± standard deviation or medians when appropriate. M, male; F, female; RL, relapse; ΔIST, change in immunosuppressive therapy; NA, not available.
↵Baseline and 12 month anti-PLA2R levels were significantly lower in group 1 than in group 2 (aP = 0.001; bP < 0.001). There were no other statistically significant differences between groups 1 and 2.
↵cTwelve-month serum samples were not available for subjects 24 and 25. They are included in group 2 for the purposes of this table, but they are not included in the statistical analyses or the summary data because we were unable to determine if there was a response in anti-PLA2R or not.
↵dThese two patients had faint visible bands that fell below the detection threshold of 1000 densitometric units when assayed at 1:25.
↵eThese bands were undetectable at a 10-second exposure but were visible at longer exposures; the anti-PLA2R level was extrapolated by calculating percentage of baseline value at the 10-second and longer exposure.
↵f“Limited” response (>50% decrease from baseline proteinuria but still >3.5 g/d).
Anti-PLA2R Autoantibodies and Response to Rituximab Treatment in Membranous Nephropathy
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