Beta-arrestin and arrestin are recognized by autoantibodies in sera from multiple sclerosis patients.

Abstract

Multiple sclerosis (MS), one of the most common chronic neurologic diseases, is characterized by the presence of multiple plaques of demyelination throughout the central nervous system. Although the etiology of the disea has not been established, it is believed to involve autoimmune mechanisms. We have examined sera from patients with MS for the presence of antibodies to antigens from brain and retina. Immunoblot analysis of the soluble fraction of proteins from bovine brain revealed a prominent band at 45 kDa stained with sera of 8-14 patients with MS. In two patients with MS, serum antibody titers during relapse were higher compared with those when the patients were in remission. These antibodies were undetectable in cerebrospinal fluid of our MS patients and additionally were absent in sera of patients with other neurological diseases and normal control subjects. Furthermore, immunoblot analysis of the soluble fraction from bovine retinal rod outer segments revealed a prominent protein band at 48 kDa stained with MS sera. This antigen was purified to homogeneity from bovine retinal outer segments and identified as arrestin. Additionaly, sera from MS patients reacted with purified 03arrestin 1, a 45-kDa protein homologous to arrestin that is found in various tissues. Using limited proteolysis of arrestin and a competitive ELISA test with a synthetic peptide, we identified the recognition site(s) for antibodies in sera of MS patients at a dominant immunogenic site on arrestin located at the C-terminal region of the molecule. We suggest that the presence of circulating antibodies reactive with -arrestin or arrestin may be related to the course of MS progression.

Enolase and Arrestin are Novel Nonmyelin Autoantigens in Multiple Sclerosis

“…It is well known that MS is associated with intermediate uveitis (26)(27)(28) and arrestin can be used to induce experimental autoimmune uveoretinitis (EAU) (29)(30)(31). Autoantibodies to both brain and retina arrestin have been reported in MS patients (11,32,33), although the T-cell proliferative response to this antigen has not been reported.…”

Desensitization of G Protein–coupled Receptors and Neuronal Functions

“…Altogether, these findings suggest that βarrestin-1 may be important for at least some of the behavioral manifestations of acute and chronic morphine. It is important to note also that a presence of circulating autoantibodies reactive with βarrestin-1 has been described in multiple sclerosis patients (Ohguro et al 1993).…”

Dynamic BRG1 Recruitment during T Helper Differentiation and Activation Reveals Distal Regulatory Elements

“…Differentiated T helper cells from miR-155-null mice produced more IL-4 and IL-5, whereas IFN-␥ levels were reduced, suggesting that miR-155 plays a role in T helper polarization (10,66,78). Th17 differentiation and multiple sclerosis (MS) were found to be regulated by miR-326 expression; MS was also linked to the overlapping beta-arrestin gene (18,56,68). miR-146a was found to be misregulated in cases of systemic lupus erythematosus (76).…”