Immunotherapy treatments for nephrological autoimmune illnesses may help treat serious Coronavirus

Immunotherapy treatments for nephrological autoimmune illnesses may help treat serious Coronavirus


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  • Source: ERA-EDTA

  • Date: 08 Jun,2021

Various viruses and bacteria have been known to cause autoimmune diseases where there’s such a predisposition. This phenomenon also seems to play a major part SARS-CoV-2, especially in severe courses. The body’s own immune cells are activated, with the formation of autoantibodies that attack the body’s own healthy cell structures (proteins, autoantigens); deposits of immune complexes can then activate severe inflammatory processes and cell destruction in the body.

Some nephrological diseases are also of autoimmunological etiology, one instance being systemic lupus erythematosus (SLE), a chronic, mostly relapsing-remitting inflammatory disease with life threatening courses sometimes. Manifestations happen on the skin and in organs such as the lungs, heart, CNS, muscles/joints – and the kidneys. Lupus nephritis (kidney inflammation) occurs in nearly three out of four cases and decides the outcomes of SLE. Many SLE patients are treated or co-managed by nephrologists, with the aim of preventing chronic kidney disease and the necessity for chronic dialysis therapy.

The causes of SLE are multifactorial (e.g. genetic predisposition, hormonal and environmental triggers). In SLE, antiphospholipid antibodies (aPLs; i.e., autoantibodies against phospholipid-binding proteins) are usually found, but also in other autoimmune diseases of the circulatory system presenting variable clinical pictures. APLs can interfere with the clotting system, so there is generally a propensity to thrombosis, and acute complications in pregnancy are also possible in affected women.

An increasing number of similarities between severe COVID-19 and SLE or autoimmune diseases have been described. APLs have also been detected in COVID-19 patients, and aPL concentrations correlated with the severity of this disease. Additionally, there are some intriguing clinical trials: A pioneering study from Germany indicates that early kidney involvement (proteinuria, hematuria) can determine outcomes in COVID-19 patients as is the case with SLE.

A new study on the topic has been released by the working group led by Prof. Wolfram Ruf, Mainz, in the renowned journal Science. The study revealed for the first time that antiphospholipid antibodies bind to the’EPCR LBPA’ complicated. This molecule complex is situated at the biochemical interface of the innate immune or pathogen defense system and the clotting system.

It’s a lipid-protein receptor complex consisting of endosomal LBPA (lysobisphosphatidic acid from endosomes) and the EPC (endothelial protein C) receptor located on the inside surface (endothelium) of the blood vessels. Within this complex, the EPC receptor presents LBPA as a pathogenic cell surface antigen. This contributes to interferon production in immune cells and to a particular expansion of B cells, which then produce further autoantibodies in a self-reinforcing autoimmune signaling loop. Regarding treatment, the study also revealed that, in the lupus mouse model, the specific pharmacological blockade of the EPCR-LBPA signaling inhibited acute aPL-related damage.

“Even if the pathogenic mechanism and importance of autoantibody formation in COVID-19 aren’t yet fully understood, it’s possible that the autoimmune response, once triggered, could be the real cause of many severe COVID-19 courses”, commented Prof. Dr. Julia Weinmann-Menke, Mainz, the DGfN Press Officer, at the Opening Press Conference of the ERA-EDTA Congress. She and her colleagues at the universities of Mainz, Greifswald (Prof. Dr. Jens Fielitz) and Berlin are therefore planning a cooperative clinical research project to further investigate this autoimmune disease and to discover new approaches for immunological COVID-19 therapies. “Our project is based on the hypothesis that an infection-associated autoimmune response by autoantibodies is implicated in many cases of organ damage in patients with severe COVID-19,” explains Prof. Weinmann-Menke.

The study aims to establish a high-throughput test process (multiplex assay) that can be used to determine specific immune responses (immunoproteomics) to autoantigens (especially against cerebral, cardiac and renal proteins) that occur in COVID-19. The glycosylation of autoantibodies, which is known to enhance their effect in many cases, is also to be investigated.

Immunomodulatory therapies used or being tested in the treatment of nephrological autoimmune diseases such as SLE may also be successful in severe COVID-19 courses. We hope that new diagnostic options for patients will provide us with better risk assessment and more targeted therapeutic approaches, also for non-COVID-associated immune phenomena.”

Prof. Weinmann-Menke


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