Background/Purpose:

B cells are pathogenic in granulomatosis with polyangiitis (Wegener’s) (GPA). Rituximab (RTX), an anti-CD20 monoclonal antibody, is effective therapy however B cell reconstitution patterns after RTX are unknown. We present pilot data on B cell subsets in GPA patients compared to healthy controls in addition to GPA patients with active disease or remission as well as patients who are treated with RTX or non-biologic immunosuppression.

Methods:

GPA patients were enrolled into: Group I (Active), Group II (Remission) and Group III (Controls). We have currently recruited 4 patients into Group 1, 13 patients into Group 2 and 5 patients in Group 3.  Frozen peripheral blood mononuclear cells were stained with isotype control, anti-CD19, anti-CD10, anti-CD20, anti-CD27, anti-CD38 and anti-CD21 antibodies. B cell subset frequencies were measured as CD19+ cell proportions that are CD10+CD27− (immature transitional – IT), CD10−CD21+CD27− (naive), CD10−CD21+CD27+ (resting memory – RM), CD10-CD21−CD27+ (mature activated – MA), CD10−CD21−CD27− (tissue like memory-TLM) and CD20-CD38+ (plasmablasts). Median proportions were compared using the Wilcoxon rank sum test with P < 0.05 considered significant.

Results:

 In all GPA subjects (n=17), we observed a decrease in total lymphopenia (P=0.03; 45.5 vs 66.2) and significantly decreased naïve B cell frequencies (P=0.04; 28.4 vs. 70.1) as compared to controls (n=5). GPA patients with active disease (n=4) had a significantly increased proportion of IT B cells (P=0.04; 27.85 vs. 0) compared to patients in remission. Patients in remission (n=13) who had received RTX had significantly decreased naïve B cell (P=0.03; 17.6 vs. 59.45) as compared to patients receiving non-biologic immunosuppression therapy (n=6). There were no statistically significant differences between other B cell subsets when comparing GPA patients with controls, active disease with remission, and comparing RTX with non-biologic immunosuppression.

Conclusion:

Patients with GPA appear to have a skewed B cell profile compared to healthy controls and this is altered during active disease with a potentially increase in the IT B cell subset. Despite clinical remission observed with RTX, GPA patients continue to have lower frequencies of naïve B cells.  

GPA vs. controls                   Active vs. remission              RTX vs. non-RTX

Parameter**	GPA (n= 17)	Controls (n = 5)	p value	Active GPA (n = 4)	GPA in remission (n = 13)	p value	RTX group  (n = 7)	Non-RTX group  (n = 6)	p value
Total lymphocytes	45.50	66.2	0.03	39.45	53.00	0.41	53	50.35	0.94
CD19+ cells	0.70	6.43	0.16	8.52	0.70	0.62	0.15	2.17	0.23
Immature transitional	0.00	0.03	0.37	0.51	0.00	0.05	0	0	0.38
Mature activated	8.45	3.28	0.19	22.86	8.45	0.62	13.9	4.73	0.37
Resting memory	19.90	13.8	0.65	11.59	20	0.41	16.1	27.1	0.23
Tissue like memory	18.20	8.5	0.24	19.5	18.2	1.00	30	11.26	0.18
Naive	28.40	70.1	0.04	26.9	28.4	0.61	17.6	59.45	0.03
Plasmablast	5.1	2.96	0.25	0.22	0.69	0.82	3.61	0.54	0.44

** All numbers represent B cell subset frequencies

Table 1. B cell subset analyses comparing: 1) GPA patients with controls, 2) Active disease with remission and 3) patients in remission after RTX versus non-biologic immunosuppression

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/b-cell-subset-phenotypes-in-patients-with-granulomatosis-with-polyangiitis-wegeners/