Autoimmune neurologic diseases
We previously demonstrated in cross-sectional analysis that, on average, children with MS exhibited increased frequencies and pro-inflammatory responses of particular Teff subsets, and diminished Treg function such that the Teff/Treg balance was dysregulated relative to children with other (monophasic) acquired demyelinating syndromes (monoAS) and healthy controls. Whether this Teff/Treg imbalance is a stable feature, or fluctuates over time in individual children is unknown. We serially measured frequencies of the implicated CD4+CCR2+CCR5+ and CD8+CD161highTCR-Vα7.2+ MAIT Teff subsets, and the ratios of Teff to Treg (CD4+CD25hiCD127lowFOXP3+) cells, in prospectively followed children with MS and controls. Children with MS (n=14) harbored increased frequencies of the two Teff subsets (p=0.021, and p=0.008), yet deficient Treg suppressive capacity (p=0.041), including diminished capacity to suppress the implicated Teff (p=0.01), compared to children with monoADS (n=7). In turn, the implicated Teff of MS patients were relatively resistant to suppression by normal Tregs (p=0.008). An abnormal Teff/Treg ratio at the individual level best distinguished MS children from controls (p<0.001). In a subset of serially studied children (n=10), Teff/Treg ratios of the individual children were relatively stable over a 3-5 period, in both MS and controls. Overall, we find that higher ratios persist in MS patients over time whether during or between relapses. Although further analyses are ongoing, we posit that the elevated Teff/Treg ratios in children with MS may reflect intrinsic abnormalities in their immune response propensities as opposed to transient abnormalities associated with emergence of disease relapse.