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Measles virus polypeptide-specific antibody profile in multiple sclerosis
S Dhib-Jalbut1, K Lewis, E Bradburn
1Neuroimmunology Branch, NINDS, NIH, Bethesda, MD 20892.
Abstract:
Elevated antibody (Ab) titers to measles virus (MV) is a frequent finding in MS. Although MV-Abs are synthesized intrathecally, it is not known whether this is due to polyclonal activation of B cells recruited from the blood, recognition of MV antigens within the CNS, or cross-reactivity with myelin antigens. This study examined these possibilities using purified MV polypeptides. We examined Ab reactivity to each polypeptide in serum and CSF from 21 MS patients, 5 with subacute sclerosing panencephalitis (SSPE), and 11 patients with other neurologic diseases (OND), and serum from 5 patients with acute MV infection and 11 normal controls. The serum of all subjects tested contained reactivity with MV and the 5 polypeptides. Of 21 MS patients, 20 had CSF reactivity with MV compared with 3/11 ONDs and 5/5 SSPE patients. Intrathecal MV-Ab synthesis was present in 11/21 MS patients, 5/5 SSPE, and in none of the ONDs. Nine of 21 MS patients had intrathecal synthesis of Ab to 2 MV polypeptides. Serum and CSF reactivity in MS patients was skewed towards the F polypeptide. The results are consistent with the concept of polyclonal B cell activation within the CNS, but the heightened response to F could also reflect cross-reactivity with a relevant antigen in MS.
Insights
Measles virus (MV) antibodies are often found in multiple sclerosis (MS). This study suggests intrathecal B cell activation in MS, potentially linked to MV or cross-reactivity with CNS antigens.
Area of Science:
- Neuroimmunology
- Virology
- Immunology
Background:
- Elevated measles virus (MV) antibody titers are common in multiple sclerosis (MS).
- The origin of intrathecal MV antibodies in MS remains unclear, with hypotheses including B cell activation, direct MV antigen recognition, or molecular mimicry with myelin antigens.
Purpose of the Study:
- To investigate the source of intrathecal MV antibodies in MS by examining reactivity to specific MV polypeptides.
- To differentiate between polyclonal B cell activation and antigen-specific responses within the central nervous system (CNS).
Main Methods:
- Analysis of antibody reactivity against purified MV polypeptides in serum and cerebrospinal fluid (CSF).
- Comparison of antibody profiles in MS patients, subacute sclerosing panencephalitis (SSPE) patients, other neurologic disease (OND) patients, acute MV infection, and healthy controls.
- Assessment of intrathecal antibody synthesis using established methods.
Main Results:
- All subjects showed serum reactivity to MV and its polypeptides.
- CSF reactivity to MV was significantly higher in MS patients (20/21) and SSPE patients (5/5) compared to OND patients (3/11).
- Intrathecal MV antibody synthesis was confirmed in 11/21 MS patients and 5/5 SSPE patients, with 9/21 MS patients showing intrathecal synthesis against specific MV polypeptides, particularly the F polypeptide.
Conclusions:
- The findings support the hypothesis of polyclonal B cell activation within the CNS in MS.
- The heightened response to the MV F polypeptide may indicate cross-reactivity with an endogenous antigen relevant to MS pathogenesis.
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