Table 2.

Proposed future B-cell-targeted strategies for management of ISN/RPS Class III/IV ± V LN

Proposed regimen	Target	Timeline	Expected response
1	Proteasome inhibitor	At flare	Deplete plasma cells and plasmablasts Stop autoantibody production Attenuate inflammatory cytokine production Attenuate Type-1 interferon activity
	Anti-CD20	At flare	Deplete B-cells and prevent autoreactive plasma cell generation
	Anti-BAFF/APRIL	Post-peripheral B-cell depletion	Prevent autoreactive B-cell repopulation
2	Anti-CD19	At flare	Stop autoantibody production Deplete effector B-lineage cells (B-cells, plasma cells, plasmablasts)
	Pulse methylprednisolone	At flare	Control inflammation
	Anti-BAFF/APRIL	Post-peripheral B-cell depletion	Prevent autoreactive B-cell repopulation
3a	Anti-CD20	At flare	Deplete B-cells and prevent autoreactive plasma cell generation
	Pulse methylprednisolone	At flare	Control inflammation
	MMF/cyclophosphamide	At flare	Suppress other immune effector cells (T-cells, monocytes/macrophages)
	MMF	Maintenance	Provide ongoing generalized immunosuppression

^aIn Regimen 3, if the anti-CD20 agent is given as a loading regimen, that is expected to deplete peripheral B-cells and there is no further anti-CD20 dosing, we suggest MMF be given after anti-CD20 and continued for maintenance; if the anti-CD20 agent is continued for two doses beyond loading we suggest cyclophosphamide be given in between anti-CD20 doses and possibly no maintenance immunosuppression will be needed.