Regulatory T lymphocytes/Th17 lymphocytes imbalance in autism spectrum disorders: evidence from a meta-analysis

Immune system dysfunction has been proposed to play a critical role in the pathophysiology of autism spectrum disorders (ASD). Conflicting reports of lymphocyte subpopulation abnormalities have been described in numerous studies of patients with ASD. To better define lymphocytes abnormalities in ASD, we performed a meta-analysis of the lymphocyte profiles from subjects with ASD.

We used the PRISMA recommendations to query PubMed, Embase, PsychoINFO, BIOSIS, Science Direct, Cochrane CENTRAL, and Clinicaltrials.gov for terms related to clinical diagnosis of ASD and to lymphocytes' populations. We selected studies exploring lymphocyte subpopulations in children with ASD. The search protocol has been registered in the international Prospective Register of Systematic Reviews (CRD42019121473).

We selected 13 studies gathering 388 ASD patients and 326 healthy controls. A significant decrease in the CD4+ lymphocyte was found in ASD patients compared to controls [- 1.51 (95% CI - 2.99; - 0.04) p = 0.04] (I² = 96% [95% CI 94.6, 97.7], p < 0.01). No significant difference was found for the CD8+ T, B and natural killer lymphocytes. Considering the CD4+ subpopulation, there was a significant decrease in regulatory T lymphocytes (Tregs) in ASD patients (n = 114) compared to controls (n = 107) [- 3.09 (95% CI - 4.41; - 1.76) p = 0.0001]; (I² = 90.9%, [95% CI 76.2, 96.5], p < 0.0001) associated with an increase oin the Th17 lymphocytes (ASD; n = 147 controls; n = 128) [2.23 (95% CI 0.79; 3.66) p = 0,002] (I² = 95.1% [95% CI 90.4, 97.5], p < 0.0001).

Several factors inducing heterogeneity should be considered. First, differences in the staining method may be responsible for a part in the heterogeneity of results. Second, ASD population is also by itself heterogeneous, underlying the need of studying sub-groups that are more homogeneous.

Our meta-analysis indicates defects in CD4+ lymphocytes, specifically decrease oin Tregs and increase in Th17 in ASD patients and supports the development of targeted immunotherapies in the field of ASD.