Peripheral blood mononuclear cells and plasma were collected from 7 treatment refractory, acetylcholine receptor autoantibody positive (AChR+) generalized MG patients before and after eculizumab treatment (6 females,1 male). Other immunosuppressive treatments remained stable after starting eculizumab. Peripheral blood mononuclear cells were stained using a 28-color flow cytometry panel that identifies and phenotypes immune subsets.

Following eculizumab therapy, we observed a ≥60% reduction in total MG-Manual Muscle Test (MMT) score in 5 of 7 AChR+ MG patients. The mean MG-MMT score decreased from 29.3 to 9.1 and mean total MG-Activities of Daily Living (ADL) score decreased from 7 to 3. Among common T cell subsets, immune profiling revealed an overall modest decrease in CD4 T cell frequency (68.9 to 63.0%), which was complemented by an increased frequency of CD8 T cells (26.2 to 29.8%). Cluster analysis of the high-dimensional dataset identified two subpopulations of CD8 T cells that increased post-eculizumab therapy. One population demonstrated a naïve profile with expression of CD45RA, CCR7, CD28, and low expression of Tbet and Eomesodermin transcription factors. The other CD8 T cell population that increased post-treatment exhibited a terminal effector phenotype with expression of KLRG1, TIGIT, Tbet, and Eomesodermin.

AChR+ MG patients receiving eculizumab therapy demonstrated a decrease in total MG-MMT and MG-ADL scores. Immunologically, eculizumab increased the frequency of selected CD8 T cells subsets and unbiased cluster analysis revealed that this increase stems from a rise in naïve and terminal effector CD8 T cells. Ongoing analyses will focus on less common immune subsets and qualitative immune signature changes in patients with a reduced clinical response to complement inhibition.