HLA TYPING IN ACUTE OPTIC NEURITIS - RELATION TO MULTIPLE-SCLEROSIS AND MAGNETIC-RESONANCE-IMAGING FINDINGS

Objective: To study the association of brain magnetic resonance imagin g (MRI) findings and HLA findings to clarify the relationship between monosymptomatic optic neuritis (ON) and ON as part of clinically defin ite multiple sclerosis (CDMS). Design: Population-based cohort of pati ent with ON referred prospectively during 6 years by neurologists and ophthalmologists within 4 weeks of onset of ON.Setting: Referral cente r 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), ethn ically matched with 192 healthy volunteers. Main Outcome measures: Rel ation between the HLA-DR156, -DR17, DQA-1B, and -DQB-1B polymorphisms as defined by restriction fragment length polymorphism analysis, and p resence of plaques on T-2-weighted brain MRI. Results: The frequency o f 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 contro l (23%) groups. The frequencies of HLA-DQA-1B (55% in ON + CDMS, 58% i n ON) and HLA-DON) and HLA-QB-1B (49% in ON + CDMS, 59% in ON) were si gnificantly increased compared with control subjects (41%, HLA-DQA-1B; 36%, HLA-DQB-1B). Brain MRI was abnormal in 48 of 56 examined patient s 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 pat ients with and without demyelinating lesions. However, patients with O N and normal MRI findings did not show association with HLA-DR15. Conc lusions: The frequencies of alleles were similar in patients with ON a nd ON + CDMS, confirming that they are not 2 immunogenetically distinc t disease entities. The heterogeneity within the group of patients wit h ON suggests that HLA-DR15 molecule is involved in susceptibility to initial demyelinating lesion formation.