Plasma cells driving inflammation

Chen D, Ireland SJ, Davis LS, Kong X, Stowe AM, Wang Y, White WI, Herbst R, Monson NL.Autoreactive CD19+CD20- Plasma Cells Contribute to Disease Severity of Experimental Autoimmune Encephalomyelitis.Chen D, Ireland SJ, Davis LS, Kong X, Stowe AM, Wang Y, White WI, Herbst R, Monson NL.
J Immunol. 2016. pii: 1501376. [Epub ahead of print]

The contribution of autoantibody-producing plasma cells in multiple sclerosis (MS) remains unclear. Anti-CD20 B cell depletion effectively reduces disease activity in MS patients, but it has a minimal effect on circulating autoantibodies and oligoclonal bands in the cerebrospinal fluid. Recently we reported that MEDI551, an anti-CD19 mAb, therapeutically ameliorates experimental autoimmune encephalomyelitis (EAE), the mouse model of MS. MEDI551 potently inhibits pathogenic adaptive immune responses, including depleting autoantibody-producing plasma cells. In the present study, we demonstrated that CD19 mAb treatment ameliorates EAE more effectively than does CD20 mAb. Myelin oligodendrocyte glycoprotein-specific Abs and short-lived and long-lived autoantibody-secreting cells were nearly undetectable in the CD19 mAb-treated mice, but they remained detectable in the CD20 mAb-treated mice. Interestingly, residual disease severity in the CD20 mAb-treated animals positively correlated with the frequency of treatment-resistant plasma cells in the bone marrow. Of note, treatment-resistant plasma cells contained a substantial proportion of CD19+CD20-plasma cells, which would have otherwise been targeted by CD19 mAb. These data suggested that CD19+CD20- plasma cells spared by anti-CD20 therapy likely contribute to residual EAE severity by producing autoreactive Abs. In patients with MS, we also identified a population of CD19+CD20-B cells in the cerebrospinal fluid that would be resistant to CD20 mAb treatment.

So we are waiting to see if anti-CD20 will become a treatment of MS. The effects on relapsing MS look as good as found with alemtuzumab and there appears to be an effect, probably in active, PPMS. However a through-away comment by Prof Hauser was that he had been treating many relapsing MSers with rituximab and many had become secondary progressive. Were is the data I ask?, but if true then maybe there is room for improvement. CD19 antibodies hit more than anti-CD20 antibodies and may be more active in animal models than with anti-CD20. This is not hard as the models are really T cell dependent and anti-CD20 does not do too much unless it causes loss of T cells.  In this paper they think that the effect of control of the disease is based on the level plasma cells (antibody secreting cells). In this study it is indicated that that CD19+, CD20- plasma cells are important. These types of cell can be found in MS, but many plasma cells do not  express CD19. However it says try get rid of plasma cells and maybe that will inhibit inflammation. Can we do this….I believe we can.

What is happening to anti CD19 in MS, if we look on clinical there is a trial but on the med immune web site, there is nothing to be seen about trials in multiple sclerosis, so will we ever know?

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