HLA, PTPN22 and PD-1 associations as markers of autoimmunity in neuromyelitis optica

Asgari, Nasrin; Nielsen, Christian Skovgaard; Stenager, Egon; Kyvik, Kirsten Ohm; Lillevang, Søren Thue

doi:10.1177/1352458511417480

Cited by 45 publications

(62 citation statements)

References 39 publications

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“…NMO has also been reported to aggregate within families and several loci have been identified as potentially relevant22 23 Large multicenter genome-wide associated studies are needed to provide further insights into the genetic background of NMO.…”

Section: Epidemiology and Demographymentioning

confidence: 99%

Overlapping CNS inflammatory diseases: differentiating features of NMO and MS

Juryńczyk

Craner

Palace

2014

J Neurol Neurosurg Psychiatry

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Neuromyelitis optica (NMO) has long been considered as a variant of multiple sclerosis (MS) rather than a distinct disease. This concept changed with the discovery of serum antibodies (Ab) against aquaporin-4 (AQP4), which unequivocally differentiate NMO from MS. Patients who test positive for AQP4-Abs and present with optic neuritis (ON) and transverse myelitis (TM) are diagnosed with NMO and those who show an incomplete phenotype with isolated ON or longitudinally extensive TM (LETM) or less commonly brain/brainstem disease are referred to as NMO spectrum disorders (NMOSD). However, many patients, who have overlapping features of both NMO and MS, test negative for AQP4-Abs and may be difficult to definitively diagnose. This raises important practical issues, since NMO and MS respond differently to immunomodulatory treatment and have different prognoses. Here we review distinct features of AQP4-positive NMO and MS, which might then be useful in the diagnosis of antibody-negative overlap syndromes. We identify discriminators, which are related to demographic data (non-white origin, very late onset), clinical features (limited recovery from ON, bilateral ON, intractable nausea, progressive course of disability), laboratory results (cerebrospinal fluid (CSF) pleocytosis with eosinophils and/or neutrophils, oligoclonal bands, glial fibrillary acidic protein in the CSF) and imaging (LETM, LETM with T1 hypointensity, periependymal brainstem lesions, perivenous white matter lesions, Dawson's fingers, curved or S-shaped U-fibre juxtacortical lesions). We review the value of these discriminators and discuss the compelling need for new diagnostic markers in these two autoimmune demyelinating diseases of the central nervous system.

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Section: Epidemiology and Demographymentioning

confidence: 99%

Overlapping CNS inflammatory diseases: differentiating features of NMO and MS

Juryńczyk

Craner

Palace

2014

J Neurol Neurosurg Psychiatry

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“…As with other autoimmune disorders, there are potential complex genetic contributions to NMO. Several HLA variants and other polymorphisms have been identified in association with NMO (Zéphir et al, 2009; Wang et al, 2011; Asgari et al, 2012), and about 3% of patients have affected relatives (Matiello et al, 2010). NMO is associated 10–40% of the time with other autoimmune disorders, including myasthenia gravis, systemic lupus erythematous, Sjögren’s syndrome, and celiac disease (Pittock et al, 2008; Bergamaschi et al, 2009; Wandinger et al, 2010; Jarius et al, 2011; Leite et al, 2012).…”

Section: Clinical Features Of Nmomentioning

confidence: 99%

Optic neuritis in neuromyelitis optica

Levin

Bennett

Verkman

2013

Progress in Retinal and Eye Research

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Neuromyelitis optica (NMO) is an autoimmune demyelinating disease associated with recurrent episodes of optic neuritis and transverse myelitis, often resulting in permanent blindness and/or paralysis. The discovery of autoantibodies (AQP4-IgG) that target aquaporin-4 (AQP4) has accelerated our understanding of the cellular mechanisms driving NMO pathogenesis. AQP4 is a bidirectional water channel expressed on the plasma membranes of astrocytes, retinal Müller cells, skeletal muscle, and some epithelial cells in kidney, lung and the gastrointestinal tract. AQP4 tetramers form regular supramolecular assemblies at the cell plasma membrane called orthogonal arrays of particles. The pathological features of NMO include perivascular deposition of immunoglobulin and activated complement, loss of astrocytic AQP4, inflammatory infiltration with granulocyte and macrophage accumulation, and demyelination with axon loss. Current evidence supports a causative role of AQP4-IgG in NMO, in which binding of AQP4-IgG to AQP4 orthogonal arrays on astrocytes initiates complement-dependent and antibody-dependent cell-mediated cytotoxicity and inflammation. Immunosuppression and plasma exchange are the mainstays of therapy for NMO optic neuritis. Novel therapeutics targeting specific steps in NMO pathogenesis are entering the development pipeline, including blockers of AQP4-IgG binding to AQP4 and inhibitors of granulocyte function. However, much work remains in understanding the unique susceptibility of the optic nerves in NMO, in developing animal models of NMO optic neuritis, and in improving therapies to preserve vision.

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“…However, the genetics of NMO susceptibility remain largely unknown. Recently, the interleukin 17 (IL-17) and HLA-DPB1*0501 allele were reported to be associated with Asian NMO patients positive for the NMO-IgG antibody [12][13][14][15][16][17] , and there was a suggestion that the emergence of anti-AQP4 antibody is reinforced by the presence of the HLA-DPB*0501 and IL-17 allele [13,15] . In addition, CYP7A1 was reported to be associated with Korean NMO patients [18] .…”

Section: Introductionmentioning

confidence: 99%

Variants in the promoter region of CYP7A1 are associated with neuromyelitis optica but not with multiple sclerosis in the Han Chinese population

Zhao

Liu

et al. 2013

Neurosci. Bull.

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Multiple sclerosis (MS) and neuromyelitis optica (NMO) are common autoimmune demyelinating disorders of the central nervous system. The exact etiology of each remains unclear. CYP7A1 was reported to be associated with NMO in Korean patients, but this is yet to be confirmed in other populations. In this study, we used Sanger sequencing to detect SNPs in the promoter region of CYP7A1 in a population consisting of unrelated patients and controls from the Han Chinese population (129 MS; 89 NMO; 325 controls). Two known SNPs, −204A>C (rs3808607) and −469T>C (rs3824260), and a novel SNP (−208G>C) were identified in the 5'-UTR of CYP7A1. The −204A>C was in complete linkage with −469T>C and both were associated with NMO but not with MS. Results suggest that the CYP7A1 allele was associated with NMO. NMO and MS have different genetic risk factors. This further supports the emerging evidence that MS and NMO are distinct disorders.

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HLA, PTPN22 and PD-1 associations as markers of autoimmunity in neuromyelitis optica

Abstract: Patients with NMO had frequent co-existence of autoimmunity and family occurrence of NMO and MS. The PD-1.3A allele was associated with NMO. The data suggest genetic autoimmune dependency of NMO.

Cited by 45 publications

References 39 publications

Overlapping CNS inflammatory diseases: differentiating features of NMO and MS

Overlapping CNS inflammatory diseases: differentiating features of NMO and MS

Optic neuritis in neuromyelitis optica

Variants in the promoter region of CYP7A1 are associated with neuromyelitis optica but not with multiple sclerosis in the Han Chinese population

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