Welcome to the Autoimmunity 2021 Congress Calendar

Background and Aims

Synthetic 5-MER peptide (or “the peptide”) MTADV (methionine, threonine, alanine, aspartic acid, valine), derived from the sequence of a human pro-inflammatory CD44 variant, alleviates pathological inflammation in mouse models of Rheumatoid Arthritis (RA), Inflammatory Bowel diseases (IBD), Multiple (MS) and Alzheimer disease (AD). The study aim: elucidation the peptide mechanism of action.

Methods

Daily administration of the peptide by injections or oral delivery; Histopathological staining of tissue sections; Bio-luminescence analysis of the peptide therapeutic effect; Mass Spectrometry to identify the peptide targets, evaluation of clinical symptoms; Gene Set Enrichment Analysis (GSEA) and qRT-PCR of mRNA.

Results

The peptide, displayed a specific therapeutic effect. Mass Spectrometry and gel analyses revealed that amyloid proteins, including serum amyloid A (SAA) and Amyloid β (Aβ), are potential targets of the peptide. SAA attracted a special attention, because it’s involvement in RA, IBD and MS pathology and its hallmarks of chronic inflammation. Muscle paralysis of C. elegans worms, expressing the human Aβ transgene, was inhibited by the peptide. The peptide restored the learning potential of 5-FAD AD mice, expressing mutated Aβ human transgenes. The peptide prevents aggregation/fibrillation or polymer formation of SAA and it targets Aβ, presenting pathological versions of these proteins. The peptide (but not the scrambled peptide) inhibits the release of the pro-inflammatory cytokines IL-6 and IL-1β from SAA-stimulated human RA fibroblasts by blocking the polymer formation of this protein.

Conclusions

We predict that the peptide can target wide spectrum of diseases, in which amyloidogenic proteins are involved (e.g., SAA, Aβ, amylin, α-synuclein, prions).

Background and Aims

Autoimmune diseases as a collective are generally secondary to a dysregulation of the innate and/or adaptive immune systems leading to organ and/or systemic disease in a genetically and environmentally predisposed host. There is no cure for autoimmune diseases currently, but therapy is geared towards controlling the chronic systemic disease towards remission, supporting affected organs and preventing acute flares using corticosteroids, disease modifying antirheumatic drugs (DMARDs) and more recently biologic therapies.

Methods

Review of literature for evidence supporting the theory behind the immune system reboot therapy (ISRT) and its potential to cure autoimmune diseases.

Results

In theory, ISRT has the potential to cure immune mediated diseases which requires the elimination of all existing immune system memory without a bone marrow stem cell transplant, by allowing the pluripotent stem cells of the host to reboot, without reproducing the disease mimicking the original stem cell at birth since autoimmune disease are not congenital. One way in which such can be obtained is through a monitored water-only based prolonged fast of up to 30 days.

Conclusions

ISRT has a potential to completely cure immune mediated diseases. A prolonged water-only based monitored fast seems to be a potential mechanism to achieve this ideal, at least in theory.

Background and Aims

The role of helminth treatment in autoimmune diseases is constantly growing. Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease with challenging treatment options. Tuftsin phosphorylcholine (TPC) is a novel helminth-based compound that modulates the host immune network.

This study was conducted to evaluate the potential value of TPC in ameliorating lupus nephritis in a murine model and specifically to compare the efficacy of TPC to the existing first-line therapy for SLE: corticosteroids (methylprednisolone).

Methods

Lupus-prone NZBxW/F1mice were treated with TPC (5 µg/mouse), methylprednisolone (MP; 5mg/body weight) or PBS (control) three times per week once glomerulonephritis, defined as proteinuria of grade > 100 mg/dL, was established. Levels of anti-dsDNA autoantibodies were evaluated by ELISA, splenic cytokines were measured in-vitro, and the kidney microscopy was analyzed following staining.

Results

TPC and MP treatments significantly improved lupus nephritis and prolonged survival in NZBxW/F1 mice. TPC-treated mice showed a significantly decreased level of proteinuria (p<0.001) and anti-dsDNA antibodies (p<0.001) as compared to PBS-treated mice. Moreover, TPC and MP inhibited the production of the pro-inflammatory cytokines IFN-γ, IL-1β, and IL-6 (p<0.001) and enhanced expression of the anti-inflammatory cytokine IL-10 (p<0.001). Finally, microscopy analysis of the kidneys demonstrated that TPC-treated mice maintained normal structure equally to MP-treated mice.

Conclusions

This data indicates that the small molecule named TPC hinders lupus development in genetically lupus-prone mice equally as methylprednisolone in most of the cases. Hence, TCP may be employed as a therapeutic potential for lupus nephritis.

Background and Aims

Therapeutic plasma exchange (TPE) is commonly used as treatment of certain autoimmune neurological diseases (AND), which main objective is the removal of pathogenic autoantibodies. Our aim was to describe the clinical profile and the experience with the usage of TPE in patients with AND at our institution.

Methods

This is an observational retrospective study, which took into account medical records of patients with diagnosis of AND who received TPE, between 2011 and 2018. Characteristics of TPE, such as number of cycles, type of replacement solution and adverse effects, were evaluated. The modified Rankin Scale (mRS) was applied to measure clinical response after therapy.

Results

187 patients were included with the following diagnoses: myasthenia gravis (MG), n=70 (37%); Guillain Barré syndrome (GBS), n=53 (28.3%), neuromyelitis optica spectrum disorders (NMOSD), n=35 (18.7%); chronic inflammatory demyelinating polyneuropathy (CIDP), n=23 (12.2%); and autoimmune encephalitis (AE), n=6 (3.2%). The most used types of replacement solution were albumin (n=131, 70%) and succilynated gelatin (n=45, 24%). All patients received a median of five cycles. Hypotension and hydroelectrolytic disorders were the main complications. After TPE, 99 (52.9%) patients showed improvement in the mRS scores and a statistical significance (p<0.05) was seen between the admission score and after TPE for every diagnosis except for CIDP.

Conclusions

TPE has an adequate safety profile and improvement in functionality in treated patients reflects its effectiveness.

Background and Aims

Combining immunosuppressors has been proposed as a strategy to enhance treatment efficacy in Inflammatory Bowel Disease (IBD). This review aims to summarize current evidence on combinations of targeted therapies with traditional immunosuppressors or with other targeted therapies.

Methods

A literature search on PubMed and Medline databases was performed to identify relevant articles.

Results

Current evidence supports that the combination of infliximab and thiopurines is more effective than monotherapy with both agents in inducing remission in Crohn’s Disease and Ulcerative colitis, as it contributes to prevent the formation of anti-infliximab antibodies; indefinite continuation of thiopurines does not seem to be associated with additional benefit, and they should be discontinued within 12 months. Data on combinations of other biologics and traditional immunosuppressors is lacking or show conflicting results. Vedolizumab seems a potentially effective maintenance regimen after calcineurin inhibitors-based rescue therapy in acute severe ulcerative colitis, as an alternative to thiopurines. Dual Targeted Therapy, which is the combination of 2 targeted therapies, might be a reasonable choice in patients with concomitant IBD and extraintestinal manifestations, or in patients with medical-refractory IBD. However, given the paucity presented to date, it should be reserved to selected patients who lack valid alternatives. Combinations with thiopurines are associated with an increased risk of infections and lymphoma. Data on other combinations is scarcer, but no specific safety issue has emerged so far.

Conclusions

Combination therapies seem to be effective in selected patients, with an overall acceptable safety profile.