RNase as a Treatment for Autoimmune Diseases: Detrimental or Beneficial?

Systemic autoimmune diseases mainly include inflammation of multiple organs and cause devastating consequences. Hence, there is an urgent need for treatments against these diseases. Though RNase treatments seem promising in some clinical trials, researchers from Japan have uncovered some variability. In a recent study published in the Journal of Clinical Investigation Insight (JCI Insight), researchers have provided new insights into the dual, opposing actions of RNase treatment—enhancing and weakening the activation of the immune system.

The immune system defends the body by producing antibodies that bind to targets called antigens. The later-formed antibody–antigen complexes, also known as immune complexes, can be eliminated. Whereas in autoimmune diseases, the immune system produces antibodies that recognize its body components as foreign cells that need to be eliminated.

Scientists know about more than 80 autoimmune diseases. Some are well-known, while others are rare and difficult to diagnose (1^✔ ✔Trusted Source
Understanding the immunopathogenesis of autoimmune diseases by animal studies using gene modulation: A comprehensive review

Go to source). With unusual autoimmune diseases, patients suffer before getting a proper diagnosis. Most of these diseases require lifelong treatment to ease symptoms.

Some autoimmune diseases affect one organ, such as pancreatic cells in type I diabetes, but systemic autoimmune diseases involve more. In some systemic autoimmune diseases, antibodies target nuclear proteins bound to RNA molecules.

The resulting immune complexes stimulate the production of immune response factors, such as type I interferons. Because RNases can destroy RNA molecules, these RNA-containing immune complexes can be destabilized by RNases.

RNase Treatment: A Double-Edged Sword for Systemic Autoimmune Diseases

Clinical trials have tested RNase treatment as a potential therapy for systemic autoimmune diseases. The results are promising, but they also reveal that RNase treatments can stimulate the autoimmune response. To understand this phenomenon, the researchers investigated the effects of RNases on the immune response.

Researchers hypothesized that the efficacy of RNase-based treatments depends on the localization of the RNA-binding site (2^✔ ✔Trusted Source
Positive and negative regulation of the Fcγ receptor-stimulatory activity of RNA-containing immune complexes by RNase

Go to source). Indeed, in some antigens, the sites binding to antibodies and those binding to RNA are very close. Removing RNAs might allow more antibodies to bind to the antigens and, consequently, stimulate the immune response.

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The team tested the effects of RNase treatment on the production of type I interferons induced by immune complexes isolated from patients with systemic autoimmune diseases. They observed opposite effects of RNase treatment on the production of type I interferons, and the differences were directly related to the composition of the immune complexes.

Researchers also confirmed the increased binding of antibodies to antigens in immune complexes that stimulated type I interferon production in the presence of RNase (3^✔ ✔Trusted Source
The treatment strategies of autoimmune disease may need a different approach from conventional protocol: a review

Go to source). Thus, RNase likely unmasked the binding sites for the antibodies when removing RNA from antigens. As a result, more immune complexes formed and stimulated autoimmunity.

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This study provides insights into the mechanisms involved in systemic autoimmune diseases and paves a way for better treatment options for patients with these conditions.

References:

1. Understanding the immunopathogenesis of autoimmune diseases by animal studies using gene modulation: A comprehensive review - (https://pubmed.ncbi.nlm.nih.gov/31918027/)
2. Positive and negative regulation of the Fcγ receptor-stimulatory activity of RNA-containing immune complexes by RNase - (https://pubmed.ncbi.nlm.nih.gov/37432743/)
3. The treatment strategies of autoimmune disease may need a different approach from conventional protocol: a review - (https://pubmed.ncbi.nlm.nih.gov/23248391/)

Source-Medindia