Soluble HLA class I and class II antigens in patients with multiple sclerosis

Abstract

Soluble HLA class I (sHLA‐I) and soluble HLA class II (sHLA‐II) antigen levels during different stages of disease were investigated in paired serum and cerebrospinal fluid (CSF) samples from 37 patients with multiple sclerosis (MS) using ELISA and Western blot analysis. Soluble HLA‐II antigens in the serum of untreated patients with the relapsing‐remitting type of MS (RRMS) were found to be significantly elevated in acute relapse as compared to values obtained from patients under steroid treatment, in remission or healthy controls. No significant differences in circulating sHLA‐I levels could be detected. In contrast, a trend towards increased intrathecal production of sHLA‐I molecules in the CSF was observed in untreated RRMS patients in acute relapse, whereas the levels of soluble HLA‐II antigens in the CSF were below the detection limit of the ELISA method. Our observations underline the presence of systemic immune activation in MS patients, as reflected in elevated serum sHLA‐II antigen levels, and reveal a dichotomy between sHLA class I and II antigen production in the peripheral blood versus CSF in acute MS. Serial measurements of sHLA‐II antigen levels might represent a non‐invasive method to assess disease activity in MS patients.

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

“…Alterations in sHLA-I and sHLA-II levels in the serum and CSF of MS patients has been reported [12-14]. A trend toward increased production of sHLA-I in the serum and CSF was observed in MS patients after immunomodulatory therapy [15].…”

“…On the other hand, sHLA-II in the serum of untreated MS patients was found to be significantly elevated compared to values obtained from MS patients receiving corticosteroid treatment. [12] Hypothetically, one would expect the measurement of sHLA in CSF would be most likely to reflect CNS disease activity. Measurement of such a biological marker of disease activity could potentially serve as a monitor of response to immunomodulatory treatment in MS.…”

The Role of HLA in MS Susceptibility and Phenotype

“…There are numerous reports of sHLA in MS. Class I sHLA levels appear to be quite variable (Adamashvili et al 2005b;Alvarez-Cermeno et al 1992;Fainardi et al 2006Fainardi et al , 2007Filaci et al 1997;Minagar et al 2005;Morandi et al 2013); however, it has been reported that increased levels of class I sHLA correlate with beneficial effects of IFN-β1a (Minagar et al 2005) and IFN-β1b (Fainardi et al 2004) treatment in RR-MS. Significantly elevated levels of class II sHLA have also been observed in both the cerebrospinal fluid and saliva of patients with RR-MS compared to healthy individuals (Adamashvili et al 2005b;Filaci et al 1997;Ott et al 1998), and class II sHLA levels were reported to correlate with a reduction in the number of gadolinium-enhancing lesions on brain MRI ). Thus, elevated levels of sHLA could potentially play a regulatory role in resolution of lesions in RR-MS. At present, however, it is not known whether patients of all HLA subtypes can make sHLA-none of the abovementioned studies have indicated the HLA types of the patients.…”

“…It has been known for many years that soluble HLA (sHLA) molecules are present in body fluids, and levels of sHLA have been reported to be elevated in many diseases, including MS (Adamashvili et al 2005b;Alvarez-Cermeno et al 1992;Aultman et al 1999;Fainardi et al 2006Fainardi et al , 2007Fainardi et al , 2009Filaci et al 1997;Minagar et al 2005Minagar et al , 2007Ott et al 1998;Rizzo et al 2012;Weyand et al 1991). The sHLA can be derived from class I or class II HLA molecules; class I sHLA in particular have been widely studied, and there is a large body of literature describing their multiple regulatory roles (Buelow et al 1995, Spaggiari et al 2002a, b, Zavazava and Kronke 1996.…”

Potential role of soluble human leukocyte antigen-G molecules in multiple sclerosis

“…Nevertheless, conflicting results were obtained in early studies focusing on this topic because although an intrathecal synthesis associated with high levels of sHLA-I in the CSF was reported in RR MS patients with clinically active disease in one report [56], another study failed to detect any difference in CSF and serum sHLA-I values between MS and controls [57]. In addition, intrathecal production of sHLA-I was observed in RR MS patients with no association with elevated CSF levels or clinical disease activity in a subsequent study [58].…”