A large set of studies have described the presence of antibodies targeting
proteins localized in the central nervous system of autistic children.
Moreover, an accumulation of evidences tend to point the prenatal period
as a critical time where noxious events leading to autism could take place.
Therefore, these so called
anti-brain autoantibodies could be produced by the mother and be transmitted to the developing fetus
during pregnancy. Indeed, two maternal autoimmune disorders: systemic
lupus erythematosus and antiphospholipid syndrome, that give rise to autoantibody
production, could be involved in autism development.
- What are Systemic lupus erythematosus (SLE) and anti-phospholipid syndrome?
SLE is an autoimmune disease affecting several organs and significantly
increasing your risks for developing thrombotic events (blood clots formation),
especially when associated with antiphospholipid antibody production.
This disease is associated with a hyperactivation of B cells producing
a high variety of autoantibodies (more than 100 antibodies have been described to date).
Antiphospholipid syndrome is an autoimmune disease where the immune system
attacks proteins that are in the blood leading to clots formation.
These two disorders, producing autoantibodies, are very often associated.
Antiphospholipid antibodies have been found in 50% of SLE patients and
20% of APS patients have also SLE, thus leading to a striking increase
in thrombotic events (1).
- Maternal SLE, APS and autism in children: some statistics.
SLE is one of the most frequent disease reported in mothers of autistic
children with an incidence of 16% while only 2% of mothers with healthy
children are affected (2).
An European study including babies born from mothers with APS showed that
5% of them developed autism by the age of two and 7% by the age of 5 years
old (3). Another study (4) reported a high incidence of autism cases in
APS exposed children (8%), in addition to a high rate of prematurity and
small for gestational age (weight < 2500g) in these babies (17% of
- SLE and APS: autoantibodies production, neurotoxicity and disruption of
Brain development is a complex and sensitive process where
early and disruptive events can have long lasting and damaging consequences
on fetal brain development.
The central nervous system is reactive to maternal autoantibodies, as
seen in animal studies where mice injected with the sera from mothers
with autistic children developed autistic-like behavioral changes (5).
Thus prenatal exposition to autoantibodies could contribute to ASD. It
is important to point at again that
maternal antibodies can cross the placenta and reach the fetus. Furthermore, the blood-brain barrier is not fully formed in the developing
fetus and the brain is still susceptible to many immune and environmental factors.
Anti-phospholipid antibody (aPL) such as anti-β2 glycoprotein can
bind to brain tissue (6) and disrupt the connections between the neurons
(7) leading to deficit in learning and memory as well as anxiety in animal
models exposed for a prolonged time (8).
Other antibodies such as anti-DNA, anti-N-methyl-D aspartate receptor,
cross-reactive antibodies specifically present in women with systemic
lupus erythematosus, have been shown to be neurotoxic to the developing
brain in mouse models (9)
Besides the detrimental effect of autoantibodies during brain development,
SLE and APS could induce a placental vascular insufficiency that could
promote brain damage in the offspring (ischemia) and increase the risk
of developing neurodevelopment disorder.
By inducing the production of anti-brain antibodies that can injure the
developing fetal brain, it is now clear that SLE and APS put you at higher
risk for having an autistic child.
The early detection and suppression of auto-antibodies from the bloodstream
during pregnancy could help to prevent their potential noxious effects
on fetal health.
At Braverman Reproductive Immunology, we routinely screen for several auto-antibodies and we have developed
a tailored strategy to counteract and/or minimize auto-antibody production
through the pregnancy.
For more information read our blog “Rituximab and Apheresis: novel
dual therapy in use at Braverman Reproductive Immunology to prevent antibody-mediated
inflammation during pregnancy” (
- Bazzan M, Vaccarino A, Marletto F. Systemic lupus erythematosus and thrombosis.
Thromb J. 2015 Apr 23; 13:16.
- Comi AM, Zimmerman AW, Frye VH, Law PA, Peeden JN. Familial clustering
of autoimmune disorders and evaluation of medical risk factors in autism.
J Child Neurol. 1999 Jun; 14(6):388-94.
- Mekinian A, Lachassinne E, Nicaise-Roland P, Carbillon L, Motta M, Vicaut
E, Boinot C, Avcin T, Letoumelin P, De Carolis S, Rovere-Querini P, Lambert
M, Derenne S, Pourrat O, Stirnemann J, Chollet-Martin S, Biasini-Rebaioli
C, Rovelli R, Lojacono A, Ambrozic A, Botta A, Benbara A, Pierre F, Allegri
F, Nuzzo M, Hatron PY, Tincani A, Fain O, Aurousseau MH, Boffa MC. European
registry of babies born to mothers with antiphospholipid syndrome. Ann
Rheum Dis. 2013 Feb; 72(2):217-22.
- Abisror N, Mekinian A, Lachassinne E, Nicaise-Roland P, De Pontual L, Chollet-Martin
S, Boddaert N, Carbillon L, Fain O. Autism spectrum disorders in babies
born to mothers with antiphospholipid syndrome. Semin Arthritis Rheum.
2013 Dec; 43(3):348-51.
- Singer HS, Morris C, Gause C, Pollard M, Zimmerman AW, Pletnikov M. Prenatal
exposure to antibodies from mothers of children with autism produces neurobehavioral
alterations: A pregnant dam mouse model. J Neuroimmunol 2009; 211: 39–48.
- Caronti B, Calderaro C, Alessandri C, Conti F, Tinghino R, Pini C, Palladini
G, Valesini G. Serum anti-beta2-glycoprotein I antibodies from patients
with antiphospholipid antibody syndrome bind central nervous system cells.
J Autoimmun. 1998 Oct;11(5):425-9.
- Chapman J, Shoenfeld Y. Neurological and neuroendocrine-cytokine inter-relationship
in the antiphospholipid syndrome. Ann N Y Acad Sci. 2002 Jun; 966:415-24. Review
- Shoenfeld Y, Nahum A, Korczyn AD. Neuronal-binding antibodies from patients
with antiphospholipid syndrome induce cognitive deficits following intrathecal
passive transfer. Lupus 2003; 12:436–42.
- Lee JY, Huerta PT, Zhang J, Kowal C, Bertini E, Volpe BT et al. Neurotoxic
autoantibodies mediate congenital cortical impairment of offspring in
maternal lupus. Nat Med 2009; 15: 91–96.