Antibody responses following induction of antigen-specific tolerance with antigen-coupled cells

Abstract

We have recently demonstrated the safety and tolerability of a novel therapeutic regimen employing autologous blood cells chemically coupled with seven myelin peptides to induce antigen-specific tolerance in MS (ETIMS study). The aim of the current study was an extended safety analysis to assess the effect of the ETIMS approach on antibodies to common autoantigens, the myelin peptides used and common recall antigens. None of the patients showed induction of autoantibody responses. One patient had a measurable myelin peptide-specific response at baseline, which was reduced after treatment. Total immunoglobulins and recall antibody responses showed no significant change. AbstractWe have recently demonstrated the safety and tolerability of a novel therapeutic regimen employing autologous blood cells chemically coupled with seven myelin peptides to induce antigen-specific tolerance in MS (ETIMS study). The aim of the current study was an extended safety analysis to assess the effect of the ETIMS approach on antibodies to common autoantigens, the myelin peptides used and common recall antigens. None of the patients showed induction of autoantibody responses. One patient had a measurable myelin peptide-specific response at baseline, which was reduced after treatment. Total immunoglobulins and recall antibody responses showed no significant change.

Antigen-Specific Immune Tolerance in Multiple Sclerosis—Promising Approaches and How to Bring Them to Patients

“…The approach targets the highest number of antigens based on the above considerations (see Table 1, Box 1) and was safe and well tolerated in a phase 1b study in RRMS and SPMS patients with T cell reactivity against at least one of the myelin peptides (15). Mechanistic studies including immunophenotyping of immune cell populations, cytokine responses and both anti-myelin and -non-myelin autoantibodies did not show any signs of induction of autoreactivity (15,75). In patients receiving high doses a reduction of myelin peptide-specific T cell responses was observed after treatment.…”

Methodological Challenges in Protein Microarray and Immunohistochemistry for the Discovery of Novel Autoantibodies in Paediatric Acute Disseminated Encephalomyelitis

“…Antibody responses against rhMOG(1–125), myelin basic protein (MBP), and synthetic myelin peptides (MOG(1–20), MOG(35–55), MBP(13–32), MBP(83–99), MBP(111–129), MBP(146–170), and proteolipid protein PLP(139–154)) were not significantly altered between patients with MOG antibodies and the seronegative group (Figure S3). As controls, we included myelin peptide antibody reactivity from 10 adult MS patients which was recently published [16]. …”

“…Serum IgG antibodies to the recombinant human MOG extracellular Ig domain (rhMOG, amino acids 1–125), produced in Escherichia coli bacteria [27], human myelin basic protein (MBP) purified from human brain [28], and synthetic peptides MOG(1–20), MOG(35–55), MBP(13–32), MBP(83–99), MBP(111–129), MBP(146–170), and proteolipid protein [PLP(139–154)] were analysed by ELISA, as described previously [16,29,30]. …”

Therapies to Suppress β Cell Autoimmunity in Type 1 Diabetes

“…Currently, this approach is being tested in clinical trials in which MS patients receive an i.v. transfusion of ECDI-fixed peripheral blood mononuclear cells loaded with MS-relevant peptides recognized by CD4 + T cells ( 237 , 238 ).…”