Background/Purpose:

Systemic lupus erythematosus (SLE) and granulomatosis with polyangiitis (GPA) are autoimmune diseases which develop secondary to immune self-tolerance failure. Both diseases are characterised in part by the production of pathogenic autoantibodies. Although they are different clinically, genetically and immunologically, SLE and GPA may be treated successfully with rituximab, an anti-CD20 monoclonal antibody B cell depleting drug.

The repopulation of B cells post-rituximab is of interest as the timing may differ in different autoimmune diseases and may be associated with serum factors, such as B cell activating factor (BAFF), which promotes B cell survival or with characteristics of specific B cell subsets.

Methods:

A prospective longitudinal study of 12 patients with SLE and 12 patients with GPA pre-rituximab and at set intervals post-rituximab with matched autoimmune controls was conducted. Demographic, clinical and laboratory data was obtained in all patients with comparison to healthy controls. 

Flow cytometry analysis of transitional B cell, naive mature B cell and memory B cell subsets was conducted in experiments staining isolated peripheral blood mononuclear cells  with antibodies to CD19, IgD, CD27, CD24 and CD38. The expression of α4β7 integrin by B cell subsets was analysed. Plasma BAFF levels were measured by ELISA at baseline, 3 months and 6 months post-rituximab. Statistical analysis was done using GraphPad Prism version 5.

Results:

B cells were found to repopulate the blood earlier after rituximab in some cases of SLE compared to GPA. There was no statistically significant difference between the pre-rituximab CD19+ B cell percentage of total lymphocytes in SLE and GPA [p=0.37], however at 3 months and 6 months post-rituximab SLE patients had a greater population of CD19+ B cells in the peripheral blood compared to GPA patients [p=0.02, p=0.001, respectively]. Early repopulation was found to be independent of serum factors, but was related to the expression of α4β7 integrin by subsets of B cells. α4β7 integrin expression by T1 and T2 transitional B cells, naive mature B cells and memory B cells was significantly lower in SLE patients compared to GPA patients pre-rituximab [p<0.0001, p=0.0003, p=0.0008 and p=0.0005, respectively]. A separate analysis revealed significantly lower α4β7 integrin expression in the early repopulation group, defined as B cell count > 5 cells/µl  ≤ 3 months post-rituximab, compared to SLE patients who repopulated the peripheral B cell pool later [p=0.004, p=0.004 and p=0.003, p=0.7 respectively].  

Plasma BAFF levels were elevated in SLE and GPA patients pre-rituximab compared to HC [p=0.008, p=0.001 respectively] with a rise in BAFF levels detected in SLE 3 months post-rituximab [p=0.006] but no difference in SLE 6 months post-rituximab [p=0.25]. Plasma BAFF levels did not change significantly in the GPA cohort post-rituximab. Plasma BAFF levels were positively correlated with percentage transitional B cells [r=0.44, p=0.04].

Conclusion:

There may be an association between the early repopulation of the peripheral blood B cell pool, α4β7 integrin by subsets of B cells and rise in BAFF levels in a cohort of SLE patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/alterations-in-b-cell-subsets-and-baff-levels-in-autoimmune-rheumatic-diseases-treated-with-b-cell-depletion-therapy-rituximab/