Adaptive and innate immune responses in multiple sclerosis with anti-CD20 therapy: Gene expression and protein profiles.

Background: Anti-CD20 is a highly effective therapy for multiple sclerosis (MS), a disease with multiple abnormalities in function of B and T cells and innate immune cells. Anti-CD20 therapy depletes B cells, which alters antibody production and has diverse effects on B cell immunity. These changes potentially affect immunity beyond B cells in MS. Objective: Determine if anti-CD20 therapy effects non-B cell, as well as B cell, gene expression, and serum protein levels. Methods: Samples were collected from 10 healthy controls and from clinically stable relapsing-remitting MS - 10 untreated, 9 interferon- Results: Anti-CD20 therapy reduced expression of 413 total genes and 185 B-cell-regulated genes at 2  weeks vs. pre-therapy. Expression of 19 (15%) of these B cell genes returned toward baseline by 6  months, including genes for the B cell activation protein, CD79A, and for immunoglobulin A, D, and G heavy chains. Expression pathways for Th17 and CD4 regulatory T-cell (Treg) development, differentiation, and proliferation also quieted. In contrast, expression increased in Th1 and myeloid cell antiviral, pro-inflammatory, and toll-like receptor (TLR) gene pathways. Conclusion: These findings have clinical implications. B cell gene expression diminishes 2  weeks after anti-CD20 antibody infusion, but begins to rebound by 6  months. This suggests that the optimum time for vaccination is soon before reinfusion of anti-CD20 therapy. In addition, at 6  months, there is enhanced Th1 cell gene expression and induction of innate immune response genes and TLR expression, which can enhance anti-viral and anti-tumor immunity. This may compensate for diminished B cell gene expression after therapy. These data suggest that anti-CD20 therapy has dynamic effect on B cells and causes a compensatory rise in Th1 and myeloid immunity.