HLA Typing in Acute Optic Neuritis

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Abstract
Objective: To study the association of brain magnetic resonance imaging (MRI) findings and HLA findings to clarify the relationship between monosymptomatic optic neuritis (ON) and ON as part of clinically definite multiple sclerosis (CDMS). Design: Population-based cohort of patients with ON referred prospectively during 6 years by neurologists and ophthalmologists within 4 weeks of onset of ON. Setting: Referral center in the general community of greater Copenhagen (Denmark) (population, 1.5 million). Patients: A consecutive sample of 199 patients aged 12 to 59 years with ON (133 with idiopathic ON, 66 with ON+CDMS), ethnically matched with 192 healthy volunteers. Main Outcome Measures: Relation between the HLA-DR15, -DR17, -DQA-1B, and -DQB-1B polymorphisms as defined by restriction fragment length polymorphism analysis, and presence of plaques on T2-weighted brain MRI. Results: The frequency of HLA-DR15 was significantly increased in patients with ON+CDMS (52%) and ON (47%) compared with control subjects (31%). The frequency of HLA-DR17 was almost equal in the ON + CDMS (18%), ON (23%), and control (23%) groups. The frequencies of HLA-DQA-1B (55% in ON+CDMS, 58% in ON) and HLA-DQB-1B (49% in ON+CDMS, 59% in ON) were significantly increased compared with control subjects (41%, HLA-DQA-1B; 37%, HLA-DQB-1B). Brain MRI was abnormal in 48 of 56 examined patients with ON+CDMS and in 64 of 120 examined patients with ON (P<.001). In contrast, the frequencies of HLA alleles did not differ between patients with and without demyelinating lesions. However, patients with ON and normal MRI findings did not show association with HLA-DR15. Conclusions: The frequencies of alleles were similar in patients with ON and ON+CDMS, confirming that they are not 2 immunogenetically distinct disease entities. The heterogeneity within the group of patients with ON suggests that the HLA-DR15 molecule is involved in susceptibility to initial demyelinating lesion formation.