HLA typing in acute optic neuritis. Relation to multiple sclerosis and magnetic resonance imaging findings
J. L. Frederiksen, H. O. Madsen, L. P. Ryder, H. B. Larsson, N. Morling and A. Svejgaard
Department of Neurology, Glostrup University Hospital, Copenhagen, Denmark.
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.
