Anti-<i>N</i>-methyl-D-aspartate receptor and anti-ribosomal-P autoantibodies contribute to cognitive dysfunction in systemic lupus erythematosus

Massardo, Loreto; Bravo‐Zehnder, Marcela; Calderón, Jorge; Flores, Patricia; Padilla, Oslando; Aguirre, JM; Scoriels, Linda; González, Alfonso

doi:10.1177/0961203314555538

Cited by 44 publications

(34 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Numerous later studies corroborated such an association . Anti‐P autoantibodies have recently been shown to be involved, along with anti– N ‐methyl‐ d ‐aspartate receptor (anti‐NMDAR), in the cognitive impairment of SLE patients . In addition, passive‐transfer experiments in mice showed that anti‐P autoantibodies induced smell alterations , depression‐like manifestations , and memory impairment .…”

mentioning

confidence: 87%

Pathogenicity of Lupus Anti–Ribosomal P Antibodies: Role of Cross‐Reacting Neuronal Surface P Antigen in Glutamatergic Transmission and Plasticity in a Mouse Model

Segovia-Miranda

Serrano

Dyrda

et al. 2015

Arthritis & Rheumatology

View full text Add to dashboard Cite

Objective. To assess whether autoantibodies against ribosomal P (anti-P), which are possibly pathogenic in neuropsychiatric systemic lupus erythematosus (NPSLE), alter glutamatergic synaptic transmission and to what extent the cross-reacting neuronal surface P antigen (NSPA) is involved.Methods. We analyzed glutamatergic transmission and long-term potentiation (LTP) mediated by AMPA receptor (AMPAR) and N-methyl-D-aspartate receptor (NMDAR) by field excitatory postsynaptic potential (EPSP) at the CA3-CA1 synapse. AMPAR activation by patch-clamp recordings in primary ventral spinal cord neurons was analyzed. In primary hippocampal neurons, NSPA distribution was assessed by double immunofluorescence, and intracellular calcium changes were evaluated using Fura-2 AM. NSPA-LacZ reporter-knockin mice expressing a truncated NSPA were used to assess NSPA expression pattern and function in the brain using b-galactosidase staining and comparative electrophysiology, calcium responses, and water maze memory tests.Results. NSPA was expressed in the brain in hippocampal CA1, dentate gyrus and ventral, but not dorsal, CA3 regions, encompassing postsynaptic regions and partial colocalization with NMDAR. Notably, NSPA-LacZ reporter-knockin mice showed impaired memory, and decreased NMDAR activity and LTP, with neurons insensitive to anti-P autoantibodies. Anti-P autoantibodies enhanced CA1 postsynaptic transmission, increasing AMPAR and NMDAR activity and leading to LTP abrogation after prolonged (20-minute) incubation.Conclusion. Our findings indicate that the neuronal cell surface target of anti-P, NSPA, is involved in glutamatergic synaptic transmission and plasticity related to memory in the hippocampus, and mediates the deleterious effects of anti-P on these processes. Cognitive impairment, as well as other diffuse NPSLE manifestations, may develop when anti-P autoantibodies have access to brain regions coexpressing NSPA, AMPAR, and NMDAR.Neuropsychiatric systemic lupus erythematosus (NPSLE) syndromes include diffuse brain dysfunctions without overt brain inflammation, which makes

show abstract

mentioning

confidence: 87%

Pathogenicity of Lupus Anti–Ribosomal P Antibodies: Role of Cross‐Reacting Neuronal Surface P Antigen in Glutamatergic Transmission and Plasticity in a Mouse Model

Segovia-Miranda

Serrano

Dyrda

et al. 2015

Arthritis & Rheumatology

View full text Add to dashboard Cite

show abstract

“…1) SLE and Sjögren’s syndrome : Besides purely neuropsychiatric forms of SLE, subtle to major cognitive alterations were demonstrated in up to 20% of SLE patients 129 . Cognitive clinical signs in SLE are accompanied with high titers of anti-N-methyl-D-aspartate receptor (NMDA; also named NR2 glutamate receptor) and/or anti-ribosomal antibodies 130, 131 .…”

Section: The Cns Is a Major Source Of Superautoantigensmentioning

confidence: 99%

Evolution, immunity and the emergence of brain superautoantigens

Nataf¹

2017

F1000Res

View full text Add to dashboard Cite

While some autoimmune disorders remain extremely rare, others largely predominate the epidemiology of human autoimmunity. Notably, these include psoriasis, diabetes, vitiligo, thyroiditis, rheumatoid arthritis and multiple sclerosis. Thus, despite the quasi-infinite number of "self" antigens that could theoretically trigger autoimmune responses, only a limited set of antigens, referred here as superautoantigens, induce pathogenic adaptive responses. Several lines of evidence reviewed in this paper indicate that, irrespective of the targeted organ (e.g. thyroid, pancreas, joints, brain or skin), a significant proportion of superautoantigens are highly expressed in the synaptic compartment of the central nervous system (CNS). Such an observation applies notably for GAD65, AchR, ribonucleoproteins, heat shock proteins, collagen IV, laminin, tyrosine hydroxylase and the acetylcholinesterase domain of thyroglobulin. It is also argued that cognitive alterations have been described in a number of autoimmune disorders, including psoriasis, rheumatoid arthritis, lupus, Crohn's disease and autoimmune thyroiditis. Finally, the present paper points out that a great majority of the "incidental" autoimmune conditions notably triggered by neoplasms, vaccinations or microbial infections are targeting the synaptic or myelin compartments. On this basis, the concept of an immunological homunculus, proposed by Irun Cohen more than 25 years ago, is extended here in a model where physiological autoimmunity against brain superautoantigens confers both: i) a crucial evolutionary-determined advantage via cognition-promoting autoimmunity; and ii) a major evolutionary-determined vulnerability, leading to the emergence of autoimmune disorders in Homo sapiens. Moreover, in this theoretical framework, the so called co-development/co-evolution model, both the development (at the scale of an individual) and evolution (at the scale of species) of the antibody and T-cell repertoires are coupled to those of the neural repertoires (i.e. the distinct neuronal populations and synaptic circuits supporting cognitive and sensorimotor functions). Clinical implications and future experimental insights are also presented and discussed.

show abstract

“…Several antibodies are reported to be associated with cognitive dysfunction. Anti‐phospholipid antibodies, anti‐N‐methyl‐D‐aspartate (NMDA) receptor and anti‐ribosomal‐p autobodies in SLE and anti‐thyroid antibodies in Hashimoto's ensephalopathy have been reported . Moreover, antiganglioside antibodies may have a potential role in neurological manifestations of several diseases, such as neurodegenerative diseases, dementia, SLE, SS, mixed cryoglobulinemia and idiopathic systemic vasculitis .…”

Section: Introductionmentioning

confidence: 99%

Primary Sjögren's syndrome is associated with significant cognitive dysfunction

et al. 2016

View full text Add to dashboard Cite

show abstract

Anti-N-methyl-D-aspartate receptor and anti-ribosomal-P autoantibodies contribute to cognitive dysfunction in systemic lupus erythematosus

Abstract: These results reveal an association of active disease together with specific circulating autoantibodies, such as anti-NMDAR and anti-P, with cognitive dysfunction in SLE patients.

Cited by 44 publications

References 63 publications

Pathogenicity of Lupus Anti–Ribosomal P Antibodies: Role of Cross‐Reacting Neuronal Surface P Antigen in Glutamatergic Transmission and Plasticity in a Mouse Model

Pathogenicity of Lupus Anti–Ribosomal P Antibodies: Role of Cross‐Reacting Neuronal Surface P Antigen in Glutamatergic Transmission and Plasticity in a Mouse Model

Evolution, immunity and the emergence of brain superautoantigens

Primary Sjögren's syndrome is associated with significant cognitive dysfunction

Contact Info

Product

Resources

About