Table 1.
Selected therapies approved for (or under investigation for) multiple sclerosis, and their in vivo effects on the profiles and cytokine responses of B cells.
| Drug name | Main drug target(s) | Effects on peripheral B cell subsets | Changes in expression of B cell cytokines |
|---|---|---|---|
| IFN-β | IFN-βR | ⇑ CD19+ B cells (108) | ⇑ IL-10, TGF-β, IL-12p70, IL-27p28 (108, 109) |
| ⇑ CD19+CD24++CD38++ B cells (108) | ⇓ IL-1β, IL-23p19/40 (108, 109) | ||
| ⇓ % CD19+CD38−IgM−IgD− (108) | |||
| ⇓ % CD80+ B cells (107, 109) | |||
| ⇓ % CD40+ B cells (109) | |||
| Glatiramer acetate | MHC class II (126) | ⇓ CD19+ B cells (127) | ⇑ IL-10, IL-6 (127) |
| ⇓ % CD27− B cells (128) | ⇓ LTα (127) | ||
| Natalizumab | Alpha-4-integrin | ⇑ % CD19+ B cells (114–116, 129) | Unknown |
| ⇑ CD19+CD10−CD138− B cells (130) | |||
| ⇑ CD19+CD10+ pre-B cells (130) | |||
| ⇑ % CD27+IgD+ B cells (114) | |||
| ⇓% CD27−IgD+ B cells (114) | |||
| ⇑ % CD27+IgD− B cells (114) | |||
| Mitoxantrone | Type II topoisomerase (121, 131) | ⇓ CD19+ B cells (132) | ⇑ IL-10 (24) |
| ⇓ % CD27+ B cells (24) | ⇓ LTα (24) | ||
| Fingolimod | S1P1R | ⇓ CD19+ B cells (116–119) | ⇑ IL-10, ⇓TNFα (117, 120) |
| ⇓ % CD27+ CD38int-low B cells (117, 120) | |||
| ⇑ % CD27− B cells (117, 119, 120) | |||
| ⇑ % CD38+CD27−CD24+CD5+ B cells (120) | |||
| ⇑ % CD10+CD38hiCD24hi B cells (117) | |||
| Dimethyl-fumarate | Nrf2 (133) | ⇓ CD19+ B cells (124, 125) | Unknown |
| Teriflunomide | Mitonchondrial enzyme dihydroorotate dehydrogenase (DHODH) (134) | ⇓ Proliferation of T cells and B cells | Unknown |
| ⇓ Antibody titers against neoantigen but not recall antigens (135, 136) | |||
| Alemtuzumab | CD52 | ⇓ CD19+ B cells (123, 137, 138) | May result in shift in the balance between pro- and anti-inflammatory cytokine networks in B cells |
| ⇑ CD19+CD23−CD27– (after 1 month) (137) | |||
| ⇑ CD19+CD23+CD27− (after 3–12 months) (137) | |||
| Partial reconstitution of CD19+CD23+CD27+ B cells (after 12 month) (137) | |||
| ⇑ CD19+CD24hiCD38hi (at 6 months) (123) | |||
| Rituximab | CD20 | ⇓ CD19+ B cells (but not plasma cells) | ⇓ IL-6, TNFα, LTα |
| Ocrelizumab | Ofatumumab | Early reconstitution of CD27−B cells and CD19+IgD+CD38hiCD10loCD24hi B cells (6–10, 79, 98) | ⇓ GM-CSF |
| ⇑ IL-10 (11, 24, 50) | |||
| Daclizumab | IL-2R-α | ⇓ CD19+ B cells (139) | Unknown |
| No change in CD19+ B cells (140) | |||
| Atacicepta | BAFF/APRIL | ⇓ % mature B cells and plasma cells (not memory B cells) (101, 103, 105) | Unknown but may result in ⇓ IL-10 and IL-35 |
aClinical trial program of atacicept in MS was discontinued when early studies indicated treatment resulted in increased disease activity (103).