Familial multiple sclerosis: clinical, histocompatibility, and viral serological studies
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Abstract:
Evaluation of presumed "multiple sclerosis families" and comparison with recently reported families has led us to the following observations: (1) Seven of our original fourteen presumptive multiple sclerosis families had to be eliminated after personal clinical evaluation of family members failed to confirm the diagnosis in a second close relative. (2) No segregation of HLA type was noted between affected and unaffected individuals in our seven bona fide multiple sclerosis families, and no consistent segregation was noted in the twenty-eight families reported elsewhere. This supports other genetic evidence that there is not a single, major gene mapping in the HLA complex which predisposes to multiple sclerosis. (3) The DW2 antigen was increased in frequency among affected members of our families, and the A3 B7 haplotype was more frequent among affected members of other families reported. But unaffected members also tended to have an increased frequency of these same antigens. (4) No relationship was noted between HLA type and antimeasles antibody titer within our families.
Insights
Genetic analysis of multiple sclerosis families reveals no major gene in the HLA complex. While certain HLA antigens like DW2 were more frequent in affected individuals, they also appeared in unaffected relatives, suggesting complex genetic factors.
Area of Science:
- Neuroimmunology
- Human Genetics
- Epidemiology
Background:
- Multiple sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system.
- Familial aggregation of MS suggests a genetic component, with the Human Leukocyte Antigen (HLA) complex being a primary area of investigation.
- Previous studies have explored associations between specific HLA types and MS susceptibility.
Purpose of the Study:
- To evaluate familial aggregation patterns in multiple sclerosis (MS).
- To investigate the role of HLA (Human Leukocyte Antigen) genes in MS predisposition within families.
- To examine the relationship between HLA type and antimeasles antibody titers in MS patients.
Main Methods:
- Clinical re-evaluation of presumptive MS families to confirm diagnoses.
- Segregation analysis of HLA haplotypes in affected and unaffected family members.
- Frequency analysis of specific HLA antigens (e.g., DW2) and haplotypes (e.g., A3 B7).
- Correlation analysis between HLA type and antimeasles antibody titers.
Main Results:
- Seven out of fourteen initially presumed MS families were excluded due to lack of confirmed diagnoses in relatives.
- No clear segregation of HLA types was observed between affected and unaffected individuals in bona fide MS families.
- Increased frequency of DW2 antigen in affected family members and A3 B7 haplotype in other reported families was noted, but these were also found in unaffected relatives.
- No significant association was found between HLA type and antimeasles antibody titers.
Conclusions:
- The findings do not support a single, major predisposing gene for MS within the HLA complex.
- The observed associations of specific HLA antigens/haplotypes are likely due to population frequencies rather than direct MS susceptibility.
- The genetic basis of multiple sclerosis appears to be complex, involving multiple genes and environmental factors, rather than a single HLA-linked gene.