ST. LOUIS, July 2 -- African Americans with multiple sclerosis have a more robust immunologic response than whites, which may explain the greater severity of symptoms among blacks, investigators here found.
A study comparing black patients and white patients with multiple sclerosis found that the African-Americans had higher levels of immunoglobulin G (IgG) antibodies (P=0.001), and a higher IgG synthesis rate (P=0.010), indicating a more active immunologic response among blacks, reported John R. Rinker II, M.D., and colleagues in the July 3 issue of Neurology.
Action Points
- Explain to patients who ask that although multiple sclerosis is less common among blacks compared with whites, African Americans tend to have more severe disease symptoms and to progress faster to the need for a cane, walker, or wheelchair.
"These antibodies are indicators of inflammation, but we don't yet understand how inflammation is linked to prognosis," said Dr. Rinker. "No one really understands yet why inflammation levels differ from one MS patient to the next."
Dr. Rinker performed the work as a fellow at Washington University Medical Center in St. Louis, and is now at the University of Alabama at Birmingham.
Although MS is less common among African Americans than among whites, the authors noted, they tend to have more opticospinal MS, a higher rate of multifocal signs and symptoms, and more disability from the disease over time.
"Because the immune system plays a central role in the MS disease process, interethnic differences in the immune response may relate to the already described differences in clinical course," they wrote.
"The B cell-driven humoral immune response may be important to MS pathogenesis," the authors continued. "Intrathecally synthesized immunoglobulins and the presence of oligoclonal bands in the cerobspinal fluid [CSF] are commonly used tests in the diagnosis of MS, and evidence of antibody deposition can be found in many histologically examined lesions."
To determine whether there were differences in immunologic responses between blacks and whites with MS they conducted a case-control study of CSF humoral immunity in African-Americans with the disease who were treated at their center, compared with randomly selected controls consisting of Caucasian Americans with MS, in a 1:2 ratio.
They compared IgG index and synthesis rates, oligoclonal band positivity, white blood cell count, and CSF proteins in 66 black and 132 white patients with MS. They also performed a survival analysis to compare times to ambulatory assistance.
They found that measures of CSF humoral activity were all higher among African Americans, with a mean IgG index of 1.35 + 0.62, compared with 1.05 + 0.55 for whites, a mean difference of 0.30 (P=0.001).
Similarly, the median IgG synthesis rate was 13.55 mg/day for blacks with MS, compared with 8.20 mg/day for whites with MS, a median difference of 5.35 mg/day (P=0.010).
A Kaplan-Meier analysis of progression to first ambulatory assistance (cane, walker, or wheelchair) showed a median of nine years for African Americans and 17 years for Caucasian Americans, a finding consistent with earlier studies. The authors noted that "the log-rank test of differences in progression to ambulatory assistance between African Americans and Caucasian Americans was significant."
Yet when they conducted Cox proportional hazard modeling, they found that IgG index did not predict whether a patient would need earlier ambulatory assistance, despite the differences in both humoral immune response and times to ambulatory assistance.
Other factors were predictive of time to ambulatory assistance, however. These included:
- Progressive onset disease (hazard ratio 2.21, 95% confidence interval, 1.13 to 2.98)
- African American background (hazard ratio 2.02, 95% CI 1.29 to 3.16)
- Age older than 35 at onset (hazard ratio 1.83, 95% CI 1.13 to 2.98)
- Male gender (hazard ratio 1.62, 95% CI 1.00 to 2.64).
The authors acknowledged that the study was limited by its retrospective design, use of a single disability endpoint, and by the lack of information on the significance of IgG in cerebrospinal fluid in the pathogenesis of multiple sclerosis. In addition, because only patients with the CSF data were used, a selection bias of patients with atypical disease features may exist.
| Support for the study came from grants to the authors. Dr. Rinker is supported by the 2006-2007 Serono-Pfizer Clinical Fellowship of the National Multiple Sclerosis Society. Co-author Robert T. Naismith, M.D., is supported by an NIH K12 award administered by Washington University School of Medicine. Senior author Anne H. Cross, M.D., was supported in part by the Manny and Rosalyn Rosenthal-Dr. John L. Trotter Chair in Neuroimmunology. |
Primary Source
Neurology
Rinker II JR et al. Neurology 2007;69:68-72.