Highlights
- •Co-existence of autoimmunity and family occurrence of autoimmune or demyelinating disease were frequently observed.
- •Circulating autoantibodies was detected with a higher frequency in patients with the diagnosis of isolated ON (ION).
- •HLA-DQB1*0602 and HLA-DRB1*1501 were associated with the presence of OCBs in CSF in both ION and MS-ON.
Abstract
Background
Optic neuritis (ON) is an inflammatory optic neuropathy, where the genetic and autoimmune
dependency remains poorly characterized.
Objective
To investigate autoimmune and immunogenetic aspects of ON.
Method
In a prospective population-based cohort 51 patients with ON were included. At follow
up 20 patients had progressed to multiple sclerosis (MS-ON). All patients were screened
for neuronal and systemic autoantibodies. HLA genotypes and allele and genotype frequencies
of the PTPN22 C1858T and the PD-1.3 single-nucleotide polymorphisms (SNPs) were determined
and compared to a cohort of Danish blood donors, acting as healthy controls.
Results
Median follow-up was 366 days (301−430) for MS-ON patients and 375 (range 50–436)
for isolated ON (ION). Autoantibodies against myelin oligodendrocyte glycoprotein
(MOG-IgG), were positive in two patients, no patients had anti-aquaporin-4 antibodies.
Coexisting neural autoantibodies were detected in two patients and in 12 patients
other systemic autoantibodies were found. Four (8%) had other autoimmune disorders.
A family history of autoimmunity was observed in 12 (24%) and of demyelinating disease
in six patients (12%). In MS-ON patients the frequencies of HLA-DQB1*06:02 and HLA-DRB1*15:01
tended to be higher compared to controls (p = 0.08). Stratification of patients with presence of oligoclonal bands (OCB) showed
an association to the HLA-DQB1*06:02-HLA-DRB1*15:01 haplotype in ION (HLA-DQB1*06:02
and HLA-DRB1*15:01 (p = 0.03)), and in MS-ON patients (HLA-DQB1*06:02 and HLA-DRB1*15:01 (p = 0.03)). No significant associations to PTPN22 1858C/T or PD-1.3 G/A were found
in any group comparison.
Conclusions
ON patients had a general susceptibility to autoimmunity and two were MOG-IgG positive.
HLA-DQB1*06:02 and HLA-DRB1*15:01 were associated with the presence of OCB in ON patients.
Keywords
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References
- The clinical profile of optic neuritis. experience of the optic neuritis treatment trial.Arch. Ophthalmol. 1991; 109: 1673-1678
- Aquaporin-4-autoimmunity in patients with systemic lupus erythematosus: a predominantly population-based study.Mult. Scler. 2017; (1352458517699791)
- A population-based study of neuromyelitis optica in Caucasians.Neurology. 2011; 76: 1589-1595
- HLA, PTPN22 and PD-1 associations as markers of autoimmunity in neuromyelitis optica.Mult. Scler. 2012; 18: 23-30
- Paraneoplastic optic neuropathy in a patient with a non-small cell lung carcinoma: a case report.Eur. J. Ophthalmol. 2005; 15: 420-423
- HLA-DR2 dose effect on susceptibility to multiple sclerosis and influence on disease course.Am. J. Hum. Genet. 2003; 72: 710-716
- Prevalence of anti-SOX1 reactivity in various neurological disorders.J. Neurol. Sci. 2016; 369: 342-346
- HLA-A confers an HLA-DRB1 independent influence on the risk of multiple sclerosis.PLoS One. 2007; 2: e664
- Advances in DNA sequencing technologies for high resolution HLA typing.Hum. Immunol. 2015; 76: 923-927
- Multiple sclerosis.Lancet. 2002; 359: 1221-1231
- Paraneoplastic autoimmune optic neuritis with retinitis defined by CRMP-5-IgG.Ann. Neurol. 2003; 54: 38-50
- Defining the role of the MHC in autoimmunity: a review and pooled analysis.PLoS Genet. 2008; 4: e1000024
- Control of peripheral T-cell tolerance and autoimmunity via the CTLA-4 and PD-1 pathways.Immunol. Rev. 2008; 224: 166-182
- The PD-1 pathway in tolerance and autoimmunity.Immunol. Rev. 2010; 236: 219-242
- HLA typing in acute optic neuritis. Relation to multiple sclerosis and magnetic resonance imaging findings.Arch. Neurol. 1997; 54: 76-80
- Optic neuropathy as a presenting feature of systemic lupus erythematosus: two case reports and literature review.Lupus. 2011; 20: 1214-1218
- Antibodies and neuronal autoimmune disorders of the CNS.J. Neurol. 2010; 257: 509-517
- Standardized method for the detection of antibodies to aquaporin-4 based on a highly sensitive immunofluorescence assay employing recombinant target antigen.J. Neurol. Sci. 2010; 291: 52-56
- MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 2: epidemiology, clinical presentation, radiological and laboratory features, treatment responses, and long-term outcome.J. Neuroinflamm. 2016; 13: 280
- MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 1: frequency, syndrome specificity, influence of disease activity, long-term course, association with AQP4-IgG, and origin.J. Neuroinflamm. 2016; 13: 279
- Unilateral optic neuritis as the presenting symptom of human immunodeficiency virus toxoplasmosis infection.Acta Ophthalmol. 2008; 86: 459-460
- DQB1*0602 rather than DRB1*1501 confers susceptibility to multiple sclerosis-like disease induced by proteolipid protein (PLP).J. Neuroinflamm. 2012; 9: 29
- Targeting intracerebral inflammation in multiple sclerosis: is it feasible?.Acta Neuropathol. 2012; 124: 395-396
- Complement activating antibodies to myelin oligodendrocyte glycoprotein in neuromyelitis optica and related disorders.J. Neuroinflamm. 2011; 8: 184
- Oligoclonal band status in Scandinavian multiple sclerosis patients is associated with specific genetic risk alleles.PLoS One. 2013; 8: e58352
- MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 4: Afferent visual system damage after optic neuritis in MOG-IgG-seropositive versus AQP4-IgG-seropositive patients.J. Neuroinflamm. 2016; 13: 282
- Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria.Ann. Neurol. 2011; 69: 292-302
- Critical role of the programmed death-1 (PD-1) pathway in regulation of experimental autoimmune encephalomyelitis.J. Exp. Med. 2003; 198: 71-78
- Optic neuritis: prognosis for multiple sclerosis from MRI, CSF, and HLA findings.Neurology. 1998; 50: 708-714
- A population-based prospective study of optic neuritis.Mult. Scler. 2017; (1352458517734070)
- Aquaporin-4 IgG autoimmune syndrome and immunoreactivity associated with thyroid cancer.Neurol. Neuroimmunol. Neuroinflamm. 2016; 3: e252
- Optic neuritis.Lancet Neurol. 2014; 13: 83-99
- Costimulatory pathways in multiple sclerosis: distinctive expression of PD-1 and PD-L1 in patients with different patterns of disease.J. Immunol. 2009; 183: 4984-4993
- The relationship between HLA-DRB1 alleles and optic neuritis in Irish patients and the risk of developing multiple sclerosis.Br. J. Ophthalmol. 2007; 91: 1288-1292
- International consensus diagnostic criteria for neuromyelitis optica spectrum disorders.Neurology. 2015; 85: 177-189
- Meta-analysis reveals an association of PTPN22 C1858T with autoimmune diseases, which depends on the localization of the affected tissue.Genes Immunol. 2012; 13: 641-652
Article info
Publication history
Published online: March 07, 2018
Accepted:
March 1,
2018
Received in revised form:
February 18,
2018
Received:
December 28,
2017
Identification
Copyright
© 2018 Elsevier B.V. All rights reserved.
