Immunological effects of cerebral palsy and rehabilitation exercises in children

Abstract

Cerebral palsy (CP) is a group of motor disorders caused by non-progressive lesions of the premature brain with lifelong pathophysiological consequences that include dysregulation of innate immunity. Persistent inflammation with increased levels of circulating pro-inflammatory tumor necrosis factor alpha (TNF-a) is negatively associated with rehabilitation outcome in children with CP. Because of the crosstalk between innate and adaptive immunity, we investigated the effect of CP and rehabilitation exercises on the adaptive immune system in children with CP by measuring the levels of CD3⁺, CD4⁺, CD8⁺ Т-cells, and CD22⁺ B-cells and the levels of immunoglobulins. Children with CP had higher levels of CD3⁺, CD4⁺, CD8⁺ Т-cells, and CD22⁺ B-cells compared to healthy children, and the rehabilitation exercise programs produced better outcomes in terms of increased gains in motor function at an earlier age. Rehabilitation exercises performed over a month resulted in significantly decreased levels of IgA in serum and reduced numbers of B-lymphocytes and reduced IgM levels. Our study suggests that rehabilitation programs with a focus on neuroplasticity and physical exercises in children with CP can reduce both cellular and humoral immune responses.

Keywords: CD22+ B-cells; CD3, cluster of differentiation 3; CP, cerebral palsy; CRP, C-reactive protein; Children with cerebral palsy; GMFCS, Gross Motor Function Classification System for Cerebral Palsy; GMFM-88, Gross Motor Function Measure-88; IL-6, interleukin 6; IgA; IgG, immunoglobulin G; Rehabilitation; T-cells; TNF-a; TNF-a, tumor necrosis factor alpha.

Fig. 1

Trends for increased (A) TNF-a levels and significantly increased numbers of (B) leukocytes, (C) CD22⁺ B-cells, (D) IgM, (F) CD3⁺ T-cells, (G) CD4⁺ T-cells, and (H) CD8⁺ T-cells were seen in children with CP (n ​= ​23) in comparison to controls (n ​= ​15). No significant difference in the level of (E) IgG was found in children with CP. Regression lines were calculated using results from robust linear regression rlm(). ∗P ​< ​.05, ∗∗P ​< ​.01.

Fig. 2

(A) Relationship between gain in motor function and age in children with CP grouped according to severity of motor dysfunction (GMFCS) (the regression line was calculated using results from linear mixed effect regression analysis lmer()). (B) Trend for a decline in the number of CD22⁺ B-cells in a direct rosette assay in peripheral blood of children with CP over the course of rehabilitation. (C) Trend for a decrease in IgM level in serum over the course of rehabilitation. (D) Decrease in IgA in serum over the course of rehabilitation; ∗P ​< ​.05, ∗∗P ​< ​.01, ∗∗∗P ​< ​.001.