Saliva soluble HLA as a potential marker of response to interferon-β1a in multiple sclerosis:: A preliminary study

Objective: Potential surrogate markers of disease activity, including response to therapy, are particularly important in a neurological disorder such as multiple sclerosis ( MS) which often has a fluctuating course. Based upon previous studies in our laboratory, we hypothesized that measurement of soluble HLA ( sHLA) molecules class II in saliva of MS patients can serve as marker of therapeutic response to high dose interferon beta-Ia. Methods: We measured the expression patterns of sHLA-II in saliva in 17 patients with relapsing/remitting MS and compared the results to clinical course and brain MRI. For comparison purposes we also assayed the saliva sHLA-II levels in 53 normal control subjects. Solid phase ELISA was used for measurement of sHLA-I and sHLA-II concentrations at baseline and after three and six months of treatment with high dose interferon beta-Ia (IFN beta-Ia). Results: The mean saliva sHLA-II levels in MS patients was significantly higher than normal controls (354 +/- 42 unit/mL vs. 222 +/- 18 unit/mL, t= 8.16, p < 0.003). Comparison of saliva sHLA-II values before and after treatment with IFN beta-Ia revealed a consistent increase in mean concentration. The increase in saliva sHLA-II values (354 +/- 42 unit/mL at baseline versus 821 +/- 86 unit/mL at 3 months and 776 +/- 63 unit/mL at 6 months, in unit/mL, p < 0.001 for both comparisons) was associated with a stable clinical course and a decline of the number of contrast-enhancing lesions on brain MRI. Comparison of the volume of T2-weighted lesions and the number of black holes on T1-weighted images did not reveal any significant changes (during pre-treatment versus posttreatment month 6) or any correlations with saliva sHLA-II levels. Saliva sHLA-I levels were not detectable. Conclusion: Serial measurement of saliva sHLA-II may serve as a potential marker of therapeutic response to IFN beta-Ia. Larger clinical studies involving more RRMS patients over longer periods of time are needed to further test the significance and value of saliva sHLA-II as an accurate marker of therapeutic response to beta-interferons.