Table 2.

Novel autoantibodies that are potentially relevant in NPSLE

Autoantibody	Antigen	Effect of autoantibodies	Clinical findings
Anti- suprabasin [26]	Suprabasin (SBSN) gene has been originally identified in mouse and human differentiating keratinocytes as an epidermal differentiation marker. SBSN is regarded as a stratified epithelium-specific secreted protein located subcellularly in vesicles and secreted to the extracellular region.	Anti-SBSN antibodies induce the expression of genes related to astrocyte damage and IL-6 production in astrocytes stimulated with LPS. Astrocytes exposed to anti-SBSN antibodies have significantly altered senescence and autophagy pathways.	Immune complex–associated SBSN was found only in the CSF of NPSLE patients. The titre of anti-SBSN antibodies was significantly higher in the CSF of NPSLE patients compared with SLE, multiple sclerosis and normal pressure hydrocephalus. CSF anti-SBSN antibodies could be a useful marker for distinguishing NPSLE patients from SLE patients without neuropsychiatric manifestations. To date no clinical correlations have been reported.
	Stronger deposition of SBSN co-localize with glial fibrillary acidic protein (GFAP) staining in the astrocytes of NPSLE patients compared to the healthy individuals.
Anti- UCH-L1 [27]	UCH-L1 is a de-ubiquitinating enzyme. It is a neuronal cytoplasmic protein mainly expressed in large neurons such as Purkinje cells, brain stem and basal ganglia neurons, and has a 50-fold higher concentration in the brain than in other tissues. The most important function of ubiquitin protein is to regulate the ubiquitin proteasome system and synaptic remodelling. Elevated CSF and serum levels of UCH-L1 were detected in traumatic brain injury, neonatal hypoxic ischaemic encephalopathy, epilepsy and toxic encephalopathy. It could be the consequence of non-specific neuronal damage. Abnormal function of UCH-L1 is also involved in the pathogenesis of neurodegenerative diseases.	CSF anti-UCH-L1 have been detected in NPSLE but not in other conditions, indicating that specific autoimmune responses have been induced by UCH-L1 in NPSLE patients and it has been proposed as a potential biomarker of neuronal damage in NPSLE.	CSF UCH-L1 levels were found significantly increased in the severe NPSLE patients and associated with increased generalized disease activity (measured by SLEDAI-2K).
			CSF anti-UCH-L1 levels were significantly elevated in patients with NPSLE in comparison to SLE without NP involvement and other connective tissue diseases and nervous system disorders. CSF anti-UCH-L1 levels were also associated with SLE organ involvement, e.g. cardiac involvement (P = 0.043), proteinuria (P = 0.048) and haematological manifestations (P = 0.016).
			Serum anti-UCH-L1 levels were positively correlated with the matched CSF anti-UCH-L1 levels among patients with NPSLE.
anti-BC RNA [28]	Neuronal regulatory brain cytoplasmic (BC) RNAs are non-protein coding, small cytoplasmic RNAs (scRNAs), expressed in neurons and are localized to synaptodendritic domains.	Anti-BC antibodies target both primate BC200RNA and rodent BC1 RNA.	Once anti-BC RNA antibodies have gained access into CNS they induce a lack of BC1 RNA, which causes phenotypic abnormalities including: epileptogenic responses and cognitive dysfunction.
	BC RNAs control local protein synthesis by interacting with eukaryotic initiation factors (EIFs) 4A and 4B, thus repressing translation in the basal default state.	SLE anti-BC antibodies effectively compete with RNA transport factor heterogeneous nuclear ribonucleoprotein A2 (hnRNP A2) for dendritic targeting elements (DTEs) access and significantly diminish BC RNA delivery to synaptodendritic sites of function.
Anti- GAPDH [29]	GAPDH is expressed on the neuronal cell surface and is involved in cell–cell interactions. GAPDH binds to laminin, which is a component of the extracellular matrix with a prominent role in neuroplasticity. Binding of GAPDH to laminin may promote neurite extension/elongation.	Anti-GADPH antibodies block binding to laminin and/or to other adhesion and synaptic molecules in the CNS, inducing neurite retraction and impairment of neuronal plasticity.	Serum anti-GAPDH autoantibodies are increased in both SLE patients with and without NP symptoms and associated with generalized disease activity (SLEDAI-2K, ESR, IgG and IgM levels), cognitive dysfunction, increased intracranial pressure and psychiatric manifestations such as anxiety, depression and psychosis.
			In mice models (C57BL6/J mice), anti-GADPH administration resulted in behavioural changes associated with a detrimental cognitive and emotional profile.