Clinical features, outcome and HLA subtypes in Eastern patients with anti-IgLON5 disease: a multicenter study

Anti-IgLON5 disease, a rare autoimmune neurological disorder, remains understudied in Eastern populations. This study aimed to characterize the clinical characteristics, treatment responses, and long-term outcomes of Chinese patients with anti-IgLON5 disease in a multicenter Chinese cohort.

This retrospective multicenter study enrolled 24 patients with anti-IgLON5 disease confirmed by serum and/or cerebrospinal fluid antibody testing from 17 centers in China. Human leukocyte antigen (HLA) typing was performed on patient blood samples. Clinical characteristics, mRS/ICS outcomes, treatment response, relapse, and long-term outcomes were analyzed. Short-term response was defined as improvement in mRS from admission to discharge, and relapse was defined as recurrence or worsening of symptoms after initial clinical improvement.

The mean age at onset was 59.6 years. Among 18 patients who received immunotherapy, 10/18 (55.6%) met the definition of achieving a short-term response. Responders included more women (6/10 vs. 2/8), fewer patients with bulbar symptoms (4/10 vs. 5/8), and more frequently had HLA-DRB1*10:01 or HLA-DQB1*05:01 (8/10 vs. 4/8) compared with non-responders. Men aged ≥ 65 years had poorer outcomes, whereas younger men and most women responded well. Long-term follow-up was performed on 16 patients (median 18 months, range 3-60 months), and eight withdrew from follow-up. Relapse occurred in 4/16 patients (25.0%). It typically occurred about 6-12 months after discharge, often following abrupt treatment withdrawal, and was effectively controlled with re-treatment. Kaplan-Meier analysis indicated that relapse risk was the highest within the first 6 months post-discharge. Early treatment (≤ 6 months) tended to be associated with more favorable outcomes. Overall, 10/14 immunotherapy-treated patients with long-term follow-up (71.4%) showed improvement, and 7/14 (50.0%) became asymptomatic. In this cohort, HLA-DQA1*01:05 and HLA-DRB1*10:01/HLA-DQB1*05:01 were over-represented among the typed patients, and the response rate to immunotherapy was numerically higher than that in the Western population (55.6% vs. 40%). The misdiagnosis rate was 33.3%. The median diagnostic delay was 2 months (IQR, 1-12 months; range, 2 days-6 years).

As the largest cohort of anti-IgLON5 disease in China to date, this multicenter series demonstrated that Chinese and Western patients with anti-IgLON5 disease have both shared and distinct clinical characteristics. Chinese patients exhibited relatively favorable responses to early immunotherapy, relapse susceptibility requiring prolonged treatment, and potential HLA associations, offering new insight into disease management.