Epilepsy Research 129 (2017) 132–137
Contents lists available at www.sciencedirect.com
Epilepsy Research
journa l h om epa ge: www.elsevier.com/locate/epilepsyres
Investigation of neuronal auto-antibodies in systemic lupus
erythematosus patients with epilepsy
Zerrin Karaaslan
a,∗
, Esme Ekizo˘ glu
a
, Pınar Tektürk
a
, Ece Erda˘ g
b
, Erdem Tüzün
b
,
Nerses Bebek
a
, Candan Gürses
a
, Betül Baykan
a
a
Department of Neurology, Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey
b
Department of Neuroscience, Istanbul University, Institute of Experimental Medicine, Istanbul, Turkey
a r t i c l e i n f o
Article history:
Received 26 July 2016
Received in revised form
30 November 2016
Accepted 13 December 2016
Available online 14 December 2016
Keywords:
Epilepsy
Neuronal auto-antibodies
Hippocampal neuropil
Systemic lupus erythematosus
a b s t r a c t
Purpose: Epilepsy is an important feature for neuropsychiatric involvement in systemic lupus erythemato-
sus (SLE) with unknown mechanism. Our aim was to investigate the presence of neuronal auto-antibodies
(NAbs) in neuropsychiatric SLE (NPSLE).
Methods: Eighteen SLE patients (17 females, 1 male) experiencing recurrent seizures were enrolled to
this study. Their clinical characteristics, EEG and MRI findings and follow-up information were eval-
uated from their files. Antibodies against voltage-gated potassium channel (VGKC)-complex antigens,
contactin-associated protein-like 2 (CASPR-2), leucine-rich, glioma inactivated 1 (LGI1), glutamic acid
decarboxylase (GAD), N-methyl-d-aspartate receptor (NMDA-R), alpha-amino-3-hydroxy-5-methyl-4-
isoxazoleproprionic acid receptor (AMPA-R) and type B gamma aminobutyric acid receptors (GABA
B
-R)
were screened in the sera of these patients. Moreover, indirect immunohistochemistry and immunocy-
tochemistry tests were performed to reveal neuropil antibodies.
Results: Six out of 18 patients (33.3%) had various forms of NAbs. Among them, one patient had antibodies
against GAD, one patient with hippocampal sclerosis on MRI was CASPR-2 antibody positive, whereas the
remaining four patients showed hippocampal neuropil staining. We could not find a significant differ-
ence between seropositive and seronegative groups, regarding the clinical characteristics, EEG and MRI
findings.
Conclusion: This study is the first to show hippocampal neuronal staining (4/18) reflecting antibodies
against unknown neuronal cell surface antigens in SLE patients with epilepsy, besides the rare occurrence
of GAD and CASPR2 antibodies. Further prospective studies are needed to search for new NAbs and
uncover their pathogenic role in SLE associated with epilepsy.
© 2016 Elsevier B.V. All rights reserved.
1. Introduction
Systemic lupus erythematosus (SLE) is an autoimmune disease
affecting multiple organ systems. Central nervous system (CNS)
involvement is a major cause of morbidity and mortality in SLE
patients (Hanly et al., 2010). Epileptic seizures are among the most
serious neuropsychiatric manifestations of SLE and constitute one
of the diagnostic criteria for neuropsychiatric SLE (NPSLE) (Liang
∗
Corresponding author at: Istanbul University, Istanbul Faculty of Medicine,
Department of Neurology, Millet Cad 34093 Capa, Istanbul, Turkey.
E-mail addresses: zkaraaslan@gmail.com (Z. Karaaslan),
esmeekizoglu@yahoo.com (E. Ekizo˘ glu), pinartopaloglu2000@yahoo.com
(P. Tektürk), eceerdag@gmail.com (E. Erda˘ g), drerdem@yahoo.com (E. Tüzün),
nersesb@yahoo.com (N. Bebek), candangrss@gmail.com (C. Gürses),
baykanb@istanbul.edu.tr (B. Baykan).
et al., 1999). They may occur at any time in the course of the
disease, possibly by diverse mechanisms. In addition to being sec-
ondary to metabolic dysfunction, toxic effects of drugs lowering
seizure threshold or stroke, seizures are also attributable to the
primary disease activity of SLE (Andrade et al., 2008; Appenzeller
et al., 2004). Autoimmunity related prothrombotic states leading
to ischemic events or inflammatory mechanisms are considered
to play the major role in the pathogenesis of seizures in NPSLE
(Sciascia et al., 2014). A huge number of autoantibodies has been
described in SLE and there is some preliminary evidence that
antiphospholipid (aPL) antibodies, mainly lupus anticoagulant and
high titres of anticardiolipin (aCL) IgG antibodies, are associated
with epilepsy (Sherer et al., 2004). However, seizures develop only
in a subset of patients having antiphospholipid syndrome (APS),
whereas aPL-positivity occurs in all cases (Ganor et al., 2005).
Therefore, it is not well established whether these antibodies are
http://dx.doi.org/10.1016/j.eplepsyres.2016.12.006
0920-1211/© 2016 Elsevier B.V. All rights reserved.