Autoimmune Clinical Trials: A Brief Review of Recent Autoimmune Research

In 2020 and 2021, the clinical research had an almost singular focus on COVID-19. They wanted to understand it, create a vaccine, and develop ways to treat the virus. It was a worldwide pandemic – and the research community was “all hands, on deck.” Many (if not most) trials that were open at the time were temporarily closed, out on pause, or quit to preserve participant safety and direct as many resources as possible to stop the pandemic. Even today, the focus on COVID-19 is still very intense.

According to Citeline (accessed 17 May 2021), there are 4,860 trials centered on the novel coronavirus (COVID-19 or 2019-nCoV). Of those, 282 were terminated, 314 are closed, 879 were completed, 1549 are planned, and 1813 are open. To put that number in perspective, Citeline says that there are currently 38,387 trials open around the world. That means that almost 5% of all research being done right now is centered on COVID-19.

Perhaps then, it will come as no surprise that a fair volume of the autoimmune research published from 2020-2021centers on COVID-19. Here are some of the highlights:

COVID and Autoimmune

In 2021, researchers Faye et al published a study in The Journal of Rheumatology that looked at the risk of adverse events in people with autoimmune disease who were hospitalized for COVID-19 (sample size = 186). They found that people with an autoimmune disease were more likely to have comorbidity, take immunosuppressive medications, and have solid organ transplants but that they were not more likely to be admitted to the ICU, receive intubation, or pass away as a result of COVID-19.

Also in 2021, researchers Liu, Sawalha, and Lu published their research in Current Opinion in Rheumatology. They evaluated the connection between COVID-19 infection and autoimmune disorders. They concluded that “there are similarities in the immune response in both disease conditions, and organ damage in COVID-19 appears to be largely immune-mediated, similar to autoimmune diseases,” but noted that more data is needed.

COVID, Autoimmune, and Anemia

The issues surrounding simultaneous autoimmune hemolytic anemia (AIHA) and COVID-19 was also explored in research from Lopez et al that was published in May 2020 in British Journal of Haematology. They concluded that while COVID-19 has been known to cause hematological complications, the onset of AIHA is novel and should be considered in patients with severe cases of anemia.

Researchers Lazarian et al also considered AIHA and COVID-19. Their research was also published in British Journal of Haematology in May 2020. They found seven people who developed AIHA after contracting COVID-19. The researchers found that over half of the patients had indolent B lymphoid malignancy and they hypothesized that an underlying malignant B lymphoid clone may have created an environment that enabled the onset of AIHA after COVID-19. In subsequent follow-ups, all of the study participants were recovering from COVID-19.

COVID Vaccine and Autoimmune

The impact of COVID-19 vaccination on those with autoimmune diseases was also considered. Researchers Boekel et al published a paper in an April 2021 issue of the Lancet Rheumatology. Specifically, they sent a survey to people with autoimmune disorders who were participating in one of several cohort studies. They received 1727 responses from patients and 682 from controls. They found that people with autoimmune diseases were just as willing to get a COVID-19 vaccine as the controls. Also, more than 20% of participants with autoimmune diseases responded that they would get the vaccine but had concerns about the impact of their underlying autoimmune condition – reservations that could be resolved by speaking with their doctors.

mRNA Vaccines for Autoimmune

Science magazine published research in January 2021 from Krienke et al that took a different approach to vaccines and autoimmune disorders using mice. These researchers found that “systemic delivery of nanoparticle-formulated 1 methylpseudouridine-modified messenger RNA (m1Ψ mRNA) coding for disease-related autoantigens results in antigen presentation on splenic CD11c+ antigen-presenting cells in the absence of costimulatory signals,” and that “in several mouse models of multiple sclerosis, the disease is suppressed by treatment with such m1Ψ mRNA.”

Preventing Autoimmune Disorders

Not ALL of the autoimmune research published from 2020-2021 revolved around COVID-19. There were also some efforts towards preventing autoimmune disorders.

: https://pubmed.ncbi.nlm.nih.gov/32977677/

New Therapeutic Pathways

Autoimmune research in 2020-2021 also looked at new therapeutic pathways for autoimmunity sufferers.

September 2020: Researchers Eggenhuizen, Ng, and Ooi published their research in International Journal of Molecular Sciences. They conducted a review of strategies to promote immune tolerance and effectively prevent the development of autoimmune conditions.

February 2021: Researchers He et al published in Therapeutic Advances in Chronic Disease. They described the safety and efficacy of Mesenchymal stem cell (MSC) treatment for people with autoimmune liver disease (AILD) and the challenges of offering MSC therapy.

April 2021: Researchers Pandey et al published research in Scientific Reports that used mice to look at Clec16a, a known factor in several autoimmune diseases. Their results showed “a mechanistic link between CLEC16A, lipid metabolism and the immune system perturbations.”

Pathophysiology and Microbiome

In 2020-2021, some researchers looked at the pathophysiology of autoimmune diseases and their connection with the body’s microbiome. In February 2021, researchers Plichta et al published research in Genome Medicine that found that microbiome of patients with systemic sclerosis (SSc) and immunoglobulin G4-related disease (IgG4-RD) differed substantially from controls. Clostridium and oral Streptococcus were overly abundant while Alistipes and Bacteroides were lacking, and the same directionality was noticed in both diseases. Further, the microbiome of IgG4-RD and SSc were similar to those observed in patients with multiple sclerosis or rheumatoid arthritis. They concluded that these commonalities could “reveal microbial functions that offer insights into the pathophysiology of these rare diseases.”

The Future of Autoimmune Research

Autoimmune research is continually evolving – even during a pandemic. There are currently 1549 autoimmune studies planned, and the medical community is increasingly able to understand the mechanisms at play, while scientists are developing the technology that they need to put novel approaches into widespread use. Some of the findings reviewed here are in the early stages and nowhere near reaching therapeutic applications, but clinical studies are the gateway to that progress.

Resources

• Eggenhuizen, P. J., Ng, B. H., & Ooi, J. D. (2020). Treg Enhancing Therapies to Treat Autoimmune Diseases. International journal of molecular sciences, 21(19), 7015. https://doi.org/10.3390/ijms21197015
• Faye, A. S., Lee, K. E., Laszkowska, M., Kim, J., Blackett, J. W., McKenney, A. S., Krigel, A., Giles, J. T., Wang, R., Bernstein, E. J., Green, P., Krishnareddy, S., Hur, C., & Lebwohl, B. (2020). Risk of Adverse Outcomes in Hospitalized Patients With Autoimmune Disease and COVID-19: A Matched Cohort Study From New York City. The Journal of rheumatology, jrheum.200989. Advance online publication. https://doi.org/10.3899/jrheum.200989
• He, C., Yang, Y., Zheng, K., Chen, Y., Liu, S., Li, Y., Han, Q., Zhao, R. C., Wang, L., & Zhang, F. (2021). Mesenchymal stem cell-based treatment in autoimmune liver diseases: underlying roles, advantages and challenges. Therapeutic advances in chronic disease, 12, 2040622321993442. https://doi.org/10.1177/2040622321993442
• Krienke, C., Kolb, L., Diken, E., Streuber, M., Kirchhoff, S., Bukur, T., Akilli-Öztürk, Ö., Kranz, L. M., Berger, H., Petschenka, J., Diken, M., Kreiter, S., Yogev, N., Waisman, A., Karikó, K., Türeci, Ö., & Sahin, U. (2021). A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis. Science (New York, N.Y.), 371(6525), 145–153. https://doi.org/10.1126/science.aay3638
• Lazarian, G., Quinquenel, A., Bellal, M., Siavellis, J., Jacquy, C., Re, D., Merabet, F., Mekinian, A., Braun, T., Damaj, G., Delmer, A., & Cymbalista, F. (2020). Autoimmune haemolytic anaemia associated with COVID-19 infection. British journal of haematology, 190(1), 29–31. https://doi.org/10.1111/bjh.16794
• Liu, Y., Sawalha, A. H., & Lu, Q. (2021). COVID-19 and autoimmune diseases. Current opinion in rheumatology, 33(2), 155–162. https://doi.org/10.1097/BOR.0000000000000776
• Lopez, C., Kim, J., Pandey, A., Huang, T., & DeLoughery, T. G. (2020). Simultaneous onset of COVID-19 and autoimmune haemolytic anaemia. British journal of haematology, 190(1), 31–32. https://doi.org/10.1111/bjh.16786
• Pandey, R., Bakay, M., Strenkowski, B. P., Hain, H. S., & Hakonarson, H. (2021). JAK/STAT inhibitor therapy partially rescues the lipodystrophic autoimmune phenotype in Clec16a KO mice. Scientific reports, 11(1), 7372. https://doi.org/10.1038/s41598-021-86493-8
• Plichta, D. R., Somani, J., Pichaud, M., Wallace, Z. S., Fernandes, A. D., Perugino, C. A., Lähdesmäki, H., Stone, J. H., Vlamakis, H., Chung, D. C., Khanna, D., Pillai, S., & Xavier, R. J. (2021). Congruent microbiome signatures in fibrosis-prone autoimmune diseases: IgG4-related disease and systemic sclerosis. Genome medicine, 13(1), 35. https://doi.org/10.1186/s13073-021-00853-7