Identification of coronin‐1a as a novel antibody target for clinically isolated syndrome and multiple sclerosis

Abstract

Recently, we identified the mimotope UH-CIS6 as a novel candidate antibody target for clinically isolated syndrome (CIS) and relapsing-remitting (RR) multiple sclerosis (MS). The purpose of this study was to further validate UH-CIS6 as an antibody target for CIS and MS and to identify the in vivo antibody target of UH-CIS6. First, a UH-CIS6 peptide ELISA was optimized. Next, we investigated the antibody response toward UH-CIS6 in cerebrospinal fluid (CSF) from patients with CIS (n = 20), MS (n = 43) and other neurological diseases (n = 42). Immunoprecipitation of anti-UH-CIS6 antibodies on a normal human brain lysate was performed to identify the in vivo antibody target of UH-CIS6. The cellular expression of an in vivo candidate target was investigated by immunohistochemistry using MS brain tissue sections. Antibody reactivity toward UH-CIS6 was detected in a significantly increased proportion of CSF samples from CIS and RR-MS patients as compared with neurological controls (p = 0.046). We identified and confirmed coronin-1a as the in vivo antibody target for UH-CIS6. Furthermore, coronin-1a was expressed by T cells

Coronin-1A: Immune Deficiency in Humans and Mice

“…Monoclonal antibodies against Coronin-1A are being investigated as potential therapy for human autoimmune diseases and lymphoid malignancies [8, 9]. Here we report a new seventh case of human Coronin-1A deficiency and review our patient’s findings in the context of current knowledge.…”

“…Immunohistochemistry of brain samples from patients suffering from multiple sclerosis (MS) showed the presence of Coronin-1A expressing T cells and macrophages in active MS lesions, along with increased MHC class-II and reduced proteolipid protein [8]. Coronin-1A was recognized by MS patient cerebrospinal fluid (CSF) antibodies reactive to the peptide UH-CIS6 [49], suggesting Coronin-1A as a novel antibody target in the treatment of MS [8].…”

“…Coronin-1A was recognized by MS patient cerebrospinal fluid (CSF) antibodies reactive to the peptide UH-CIS6 [49], suggesting Coronin-1A as a novel antibody target in the treatment of MS [8]. …”

Circulating Follicular Regulatory T Cells Are Defective in Multiple Sclerosis

“…Moreover, elevated levels of autoantibodies have been reported in MS (29,30). In light of these findings, we investigated whether the T FR com-partment known to regulate humoral immunity is disturbed in MS. We show a decreased frequency of circulating T FR in MS patients (n = 172; for more information, see Supplemental Table I) compared with HCs (n = 107; for more information, see Supplemental Table I; p , 0.0001; Fig.…”

Coronin‐1a is a potential therapeutic target for activated T cell‐related immune disorders

“…It has been reported that coronin-1a is required for the development of systemic lupus erythematosus (4). Recently, antibody reactivity toward coronin-1a has been observed in patients with multiple sclerosis (5), which is an autoimmune disease with large amount of activated T cells in the blood and cerebrospinal fluid (6)(7)(8). Meanwhile, in ankylosing spondylitis, immunosuppression therapy with sinomenine downregulates the expression of coronin-1a in peripheral blood mononuclear cells (PBMCs) (9).…”