Regulatory T lymphocytes/Th17 lymphocytes imbalance in autism spectrum disorders: evidence from a meta-analysis
Abstract Background 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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2021-10-01
|
| Series: | Molecular Autism |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13229-021-00472-4 |
| _version_ | 1818897160966504448 |
|---|---|
| author | Pierre Ellul Michelle Rosenzwajg Hugo Peyre Gwladys Fourcade Encarnita Mariotti-Ferrandiz Vincent Trebossen David Klatzmann Richard Delorme |
| author_facet | Pierre Ellul Michelle Rosenzwajg Hugo Peyre Gwladys Fourcade Encarnita Mariotti-Ferrandiz Vincent Trebossen David Klatzmann Richard Delorme |
| author_sort | Pierre Ellul |
| collection | DOAJ |
| description | Abstract Background 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. Methods 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). Results 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] (I 2 = 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]; (I 2 = 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] (I 2 = 95.1% [95% CI 90.4, 97.5], p < 0.0001). Limitations 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. Conclusion 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. |
| first_indexed | 2024-12-19T19:11:46Z |
| format | Article |
| id | doaj.art-273e0520bd9844f18925df886b2728ed |
| institution | Directory Open Access Journal |
| issn | 2040-2392 |
| language | English |
| last_indexed | 2024-12-19T19:11:46Z |
| publishDate | 2021-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Autism |
| spelling | doaj.art-273e0520bd9844f18925df886b2728ed2022-12-21T20:09:15ZengBMCMolecular Autism2040-23922021-10-011211710.1186/s13229-021-00472-4Regulatory T lymphocytes/Th17 lymphocytes imbalance in autism spectrum disorders: evidence from a meta-analysisPierre Ellul0Michelle Rosenzwajg1Hugo Peyre2Gwladys Fourcade3Encarnita Mariotti-Ferrandiz4Vincent Trebossen5David Klatzmann6Richard Delorme7AP-HP (Assistance Publique-Hôpitaux de Paris), Robert Debré Hospital, Child and Adolescent Psychiatry Department, Paris UniversityINSERM, Immunology-Immunopathology-Immunotherapy (i3), Sorbonne UniversitéAP-HP (Assistance Publique-Hôpitaux de Paris), Robert Debré Hospital, Child and Adolescent Psychiatry Department, Paris UniversityINSERM, Immunology-Immunopathology-Immunotherapy (i3), Sorbonne UniversitéINSERM, Immunology-Immunopathology-Immunotherapy (i3), Sorbonne UniversitéAP-HP (Assistance Publique-Hôpitaux de Paris), Robert Debré Hospital, Child and Adolescent Psychiatry Department, Paris UniversityINSERM, Immunology-Immunopathology-Immunotherapy (i3), Sorbonne UniversitéAP-HP (Assistance Publique-Hôpitaux de Paris), Robert Debré Hospital, Child and Adolescent Psychiatry Department, Paris UniversityAbstract Background 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. Methods 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). Results 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] (I 2 = 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]; (I 2 = 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] (I 2 = 95.1% [95% CI 90.4, 97.5], p < 0.0001). Limitations 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. Conclusion 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.https://doi.org/10.1186/s13229-021-00472-4ASDImmunologyPeripheral bloodRegulatory T lymphocyteTh17 lymphocytes |
| spellingShingle | Pierre Ellul Michelle Rosenzwajg Hugo Peyre Gwladys Fourcade Encarnita Mariotti-Ferrandiz Vincent Trebossen David Klatzmann Richard Delorme Regulatory T lymphocytes/Th17 lymphocytes imbalance in autism spectrum disorders: evidence from a meta-analysis Molecular Autism ASD Immunology Peripheral blood Regulatory T lymphocyte Th17 lymphocytes |
| title | Regulatory T lymphocytes/Th17 lymphocytes imbalance in autism spectrum disorders: evidence from a meta-analysis |
| title_full | Regulatory T lymphocytes/Th17 lymphocytes imbalance in autism spectrum disorders: evidence from a meta-analysis |
| title_fullStr | Regulatory T lymphocytes/Th17 lymphocytes imbalance in autism spectrum disorders: evidence from a meta-analysis |
| title_full_unstemmed | Regulatory T lymphocytes/Th17 lymphocytes imbalance in autism spectrum disorders: evidence from a meta-analysis |
| title_short | Regulatory T lymphocytes/Th17 lymphocytes imbalance in autism spectrum disorders: evidence from a meta-analysis |
| title_sort | regulatory t lymphocytes th17 lymphocytes imbalance in autism spectrum disorders evidence from a meta analysis |
| topic | ASD Immunology Peripheral blood Regulatory T lymphocyte Th17 lymphocytes |
| url | https://doi.org/10.1186/s13229-021-00472-4 |
| work_keys_str_mv | AT pierreellul regulatorytlymphocytesth17lymphocytesimbalanceinautismspectrumdisordersevidencefromametaanalysis AT michellerosenzwajg regulatorytlymphocytesth17lymphocytesimbalanceinautismspectrumdisordersevidencefromametaanalysis AT hugopeyre regulatorytlymphocytesth17lymphocytesimbalanceinautismspectrumdisordersevidencefromametaanalysis AT gwladysfourcade regulatorytlymphocytesth17lymphocytesimbalanceinautismspectrumdisordersevidencefromametaanalysis AT encarnitamariottiferrandiz regulatorytlymphocytesth17lymphocytesimbalanceinautismspectrumdisordersevidencefromametaanalysis AT vincenttrebossen regulatorytlymphocytesth17lymphocytesimbalanceinautismspectrumdisordersevidencefromametaanalysis AT davidklatzmann regulatorytlymphocytesth17lymphocytesimbalanceinautismspectrumdisordersevidencefromametaanalysis AT richarddelorme regulatorytlymphocytesth17lymphocytesimbalanceinautismspectrumdisordersevidencefromametaanalysis |