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

Abstract

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-1a. 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-1a (IFN β-1a). Results:The mean saliva sHLA-ll 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 β-1a 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 β-1a. 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.

Salivary biomarkers for the diagnosis and monitoring of neurological diseases

“…In accordance with Adamashvili, Minagar et al. [217] reported, using ELISA, an increase in soluble HLA class II in the saliva of patients suffering from RRMS as compared to healthy controls and undetectable salivary soluble HLA class I concentrations. They also monitored soluble HLA class II salivary levels in response to interferon β1-a, which is a medication commonly used to manage MS. Soluble HLA class II concentrations exhibited an increase in response to interferon β1-a treatment with decline in MRI contrast enhancing lesions and a stable disease course.…”

Salivary Biomarkers: Future Approaches for Early Diagnosis of Neurodegenerative Diseases

“…This finding highlighted a direct correlation between IFN β-1a and HLA-II. In conclusion, the results demonstrated that salivary sHLA-II could be used as a biomarker for the diagnosis of MS and to evaluate the therapeutic response to IFN β-1a [91].…”

Soluble HLA peptidome: A new resource for cancer biomarkers

“…It has to be noted however that these observations differ depending on the cancer type, and could therefore be explained by different immune reactions toward various cancer types. Regardless of the abundance of sHLA, several studies confirm their presence in different body fluids ( Table 1 ) ( 31 , 32 , 34 , 35 , 37 – 42 ). Interestingly, peptides bound to these sHLA are derived from intra- and extracellular proteins expressed in the cell of origin.…”