Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
B cell depletion by rituximab (RTX)is effective treatment for ANCA-associated vasculitis (AAV). However, the phenotype of peripheral B cells and the selection criteria for RTX in AAV remain unclear. We assessed the correlation between B cell phenotype and clinical outcome of RTX therapy in AAV patients.
All AAV patients who were introduced to remission induction therapy were registered for immunophenotyping-analysis using multi-colour flow cytometry. Phenotypiccharacterization of the circulating T cells and B cells were defined by 8-color flow cytometric analysis for “Human Immunology Project” termed by NIH/FOCIS in 58 AAV patients (18 GPA and 40 MPA). Based on the judgement by physicians who do not know the result of immunophenotyping-analysis, the patients were consideredsuitable to receive immunosuppressive drugs (conventional immune suppressants group; n=28) or RTX (RTX group; n=30). All patients also received high dose glucocorticoids (GC). We assessed the phenotype of circulating T cells and B cells, the correlation between these lymphocytes and clinical findings in active AAV and evaluated the efficacy and safety outcomes at 6 months after treatment. Definition of clinical improvement was a reduction of 50% or more in BVAS in vital organs without relapse.
The proportions of naïve CD4+ T cells was higher, while that of central memory CD4+ T cells was lower, in AAV patients than healthy control (HC). Higher proportions of IgD–CD27– B cells and lower proportions of IgM memory B cells, were found in AAV patients compared with HC. The proportion of IgD–CD27–or class-switched memory B cells was increased in 23 out of 58 patients (40%) compared with HC. The rate of improvement in BVAS negatively correlated with the proportion of naive B cells and positively correlated with that of IgD–CD27–B cells. There was no correlation between the proportion of CD4+ T cell-phenotype and the rate of improvement. Twenty nine out of 30 patients (97%) in RTX group achieved clinical improvement. Among 28 patients in conventional immune suppressants group (including 20 intravenous cyclophosphamide and 8 azathioprine), 23 patients (82%) achieved clinical improvement. There was no significant difference in the rate of improvement, relapses, serious adverse events between the two treatment groups. The rate of clinical improvement in patients with excessive B cell differentiation was significantly lower than in patients withoutexcessive B cell differentiation. In the patients with excessive B cell differentiation, the rates of survival, improvement in BVAS and GC reduction were significantly higher in RTX group than in conventional immune suppressants group at 6 months after treatment.
The presence of excessive B cell differentiation was associated with treatment resistance. However,in the patients with excessive B cell differentiation,RTX was effective and showed rapid effect of GC tapering and higher survival rate compared to conventional immune suppressants. The results suggested thatmulti-color flow cytometry might be useful for the selection of RTX therapy in AAV patients.
To cite this abstract in AMA style:Miyazaki Y, Nakayamada S, Kubo S, Nakano K, Iwata S, Fukuyo S, Kawabe A, Tanaka Y. Favorable Efficacy of Rituximab in ANCA-Associated Vasculitis Patients with Excessive B Cell Differentiation [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/favorable-efficacy-of-rituximab-in-anca-associated-vasculitis-patients-with-excessive-b-cell-differentiation/. Accessed April 2, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/favorable-efficacy-of-rituximab-in-anca-associated-vasculitis-patients-with-excessive-b-cell-differentiation/