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

Alireza Minagar,Irena Adamashvili,Roger E Kelley,Eduardo Gonzalez-Toledo,Stacy J Smith,Jerry Mclarty

doi:10.1186/1742-2094-4-16

Abstract

ObjectivePotential 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.MethodsWe 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).ResultsThe 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 post-treatment month 6) or any correlations with saliva sHLA-II levels. Saliva sHLA-I levels were not detectable.ConclusionSerial 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.

Highlights

The Human Major Histocompatibility Antigens (HLA) are generally cell bound, but trace amounts exist in soluble forms which circulate in serum, plasma, and other human body fluids [1]
Preliminary evidence suggests that patients with systemic lupus erythematosus (SLE) are at increased risk of developing active disease in the presence of high soluble HLA (sHLA)-I levels in the saliva, while sHLA-II level has not been observed to be elevated in rheumatological diseases [11]
SHLA-I exists in very low quantities in the saliva, sweat, urine and/or tears of normal individuals, while sHLA-II is routinely detectable in all these body fluids [1]

Summary

Introduction

The Human Major Histocompatibility Antigens (HLA) are generally cell bound, but trace amounts exist in soluble forms which circulate in serum, plasma, and other human body fluids [1]. These soluble HLA class-I (sHLA-I) and class-II (sHLA-II) molecules may have immunomodulatory function [2,3,4]. Preliminary evidence suggests that patients with systemic lupus erythematosus (SLE) are at increased risk of developing active disease in the presence of high sHLA-I levels in the saliva, while sHLA-II level has not been observed to be elevated in rheumatological diseases [11]. SHLA-I exists in very low quantities in the saliva, sweat, urine and/or tears of normal individuals, while sHLA-II is routinely detectable in all these body fluids [1]

Methods

Results

Conclusion