Abstract
Introduction
Research describes higher incidence of neurodevelopmental disorders and learning disabilities in offspring of women affected by lupus. Factors implied are pregnancy and delivery adversities and exposure to maternal antibodies and cytokines. Little is known about the offspring immunological condition or the relation between offspring and maternal condition.
Objectives
This study was conducted in order to analyze immunological configuration, psychopathology, and neuropsychological performance of young offspring of women with lupus, in comparison with healthy controls and in relation to maternal psychophysical condition.
Methods
Twenty-one offspring aged 8–17 of 17 women with lupus and 34 controls were recruited. Pregnancy conditions, stress factors, and immunological, psychopathological, and neuropsychological characteristics were compared. Immunological tests included standard lupus screening, lupus-related autoantibodies, antibodies against GluN2 subunit of the N-methyl-D-aspartate receptor (NMDAR) (anti-DWEYS Ab), and levels of ten cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, GMCSF, IFN-γ, TNF-α).
Results
Offspring had lower leukocyte count (p = 0.001) and higher levels of anti-dsDNA Ab (p = 0.022), anti-DWEYS-GluN2 Ab (p < 0.001), and eight cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, TNF-α—all p < 0.001—and IFN-γ, p = 0.026) than controls. Their cytokine levels did not differ from their mothers’; 23.9% of offspring met the criteria for a clinical psychiatric diagnosis. No differences were found in intelligence measures. Various neuropsychological scores correlated inversely with maternal psychophysical health.
Conclusions
Offspring’s profile suggests proinflammatory and autoimmune activation. Their rate of psychiatric diagnosis appears higher than in the general population, and their cognitive performance is related to maternal psychophysical health. Longitudinal research might investigate whether immunological and psychosocial conditions influence psychopathology and cognition.
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Abbreviations
- Ab :
-
autoantibodies
- ADHD :
-
attention deficit and hyperactivity disorder
- ANA Ab :
-
anti-nuclear antibodies
- Anti-DWEYS-GluN2 Ab :
-
antibodies against the GluN2 subunit of the NMDAR
- anti-RP Ab:
-
anti-ribosomal P protein antibodies
- aPL Ab:
-
antiphospholipid antibodies
- ASD :
-
autism spectrum disorders
- ASLO Ab:
-
anti-streptolysin-O (ASLO) antibodies
- BBB :
-
blood brain barrier
- BDI :
-
Beck Depression Inventory
- BMI :
-
body mass index
- CBA :
-
cell based assays
- CDRS-R :
-
Children’s Depression Rating Scale—revised
- HADS :
-
Hospital Anxiety and Depression
- HC :
-
healthy controls
- IHC :
-
immunochemistry
- LD :
-
learning disabilities
- NMDAR :
-
N-methyl-D-aspartate receptor
- NPSLE :
-
neuropsychiatric lupus
- OCD :
-
obsessive-compulsive disorder
- OCS scale :
-
obstetrical complication scale
- SCARED :
-
Screen for Child Anxiety Related Emotional Disorders
- SES scale:
-
socioeconomic status scale
- SLE :
-
systemic lupus erythematosus
- SLEDAI scale :
-
SLE Disease Activity Index scale
- SLE-O :
-
offspring of women with SLE
- SLES-C :
-
Stressful Life Events Schedule, child version
- SLES-P :
-
Stressful Life Events Schedule—parent version
- SLICC-DI :
-
Systemic Lupus International Collaborative Clinics/American College of Rheumatology Damage Index scale
- WAIS-III :
-
Wechsler adult intelligence scale 3rd edition
- WISC- IV :
-
the Wechsler intelligence scale for children 4th edition
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Acknowledgements
The authors would like to thank Antonio Angulo, neuropsychologist, who took the neuropsychological tests; Dr. Odette Vinyas, immunologist, who contributed in running the immunological tests; and Dr. Roger Borrás for the help in the preliminary statistical analysis.
Funding
This work was partially financed by FIS (Fund for Investigation in Health) grant no. PI040700 from the Health Ministry of Spain. MG was partly supported by an “After-Specialization-Grant” (Beca de Fin de Residencia) by the Hospital Clinic Foundation.
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Gariup, M., Lera-Miguel, S., Torres, F. et al. Autoantibodies, elevated cytokines, and neurocognitive abnormalities in offspring of women with systemic lupus erythematosus: comparison with healthy controls. Clin Rheumatol 38, 2529–2539 (2019). https://doi.org/10.1007/s10067-019-04495-4
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DOI: https://doi.org/10.1007/s10067-019-04495-4