Therapy helped 13-year-old by increasing immune tolerance, researchers say
A personalized vaccine kit designed to prevent COVID-19 infection eased systemic lupus erythematosus (SLE) manifestations in an adolescent girl in Indonesia whose symptoms had not been well-controlled with immunosuppressive therapies, a study showed.
Researchers believe that while the therapy was not specifically targeted for SLE, it helped the girl by increasing immune tolerance, or the process by which the immune system recognizes the body’s own proteins and doesn’t attack them. That process is dysregulated in autoimmune diseases like SLE, where the immune system becomes self-reactive.
The vaccine was generated using the patient’s own immune dendritic cells (DCs), via a vaccine kit from Aivita Biomedical. Findings from the report suggest that the kit-made vaccine may have benefits beyond virus prevention for SLE patients, Aivita noted in a company press release announcing the publication.
“Herein, we report the first case of a patient with SLE showing significant clinical improvement after administration of the DC vaccine,” the researchers wrote. “DC immunotherapy appears to be a potential novel therapy for SLE that needs to be studied.”
The study, “Significant improvement of systemic lupus erythematosus manifestation in children after autologous dendritic cell transfer: a case report and review of literature,” was published in Therapeutic Advances in Vaccines and Immunotherapy.
DCs work by presenting foreign protein fragments, e.g., parts of a virus, to other immune cells, such as T-cells, that can then coordinate an immune attack against these fragments and the cells producing them.
While their action contributes to immune responses, certain subsets of DCs are also involved in immune tolerance, helping to mark self-reactive T-cells for death. As such, problems in these cells are thought to play a critical role in the development of SLE and other autoimmune diseases.
Aivita’s AV-COVID-19 vaccine kit aims to enable personalized dendritic cell-based vaccines against SARS-CoV-2, the virus that causes COVID-19 infection. Essentially, a person’s own immune cells are extracted from a blood sample and exposed to a protein found on the virus surface. These cells will then develop into mature dendritic cells capable of presenting this viral protein to other immune cells.
Once returned to the patient via a subcutaneous, or under-the-skin, injection, the DCs are expected to promote an immune response against the virus.
Teen wasn’t responding to standard lupus treatments
In the recently published case report, scientists administered this COVID-19-targeted vaccine to a teenage girl with SLE who was not responding to standard treatments, leading to improvements in her clinical condition.
The 13-year-old girl had been experiencing pain in all joints that was not eased with standard anti-inflammatory medication, for the past 3.5 months. She also complained of persistent fever, shortness of breath, sleep disturbances, headaches, and sores on her lips.
She was found to have abnormal blood cell counts, including decreased red blood cells and a relative increase in a group of immune cells that include T-cells. Imaging revealed fluid buildup in the chest cavity that was suspected to be dengue fever, but additional testing rejected that diagnosis.
Over the ensuing weeks, the girl continued to get worse, including a persistent fever that led to her hospitalization. This was accompanied by joint pain, weakness, coughing and swallowing pain, rashes, and low blood pressure.
She was showing poor motor function in her lower limbs, as well as eye bleeding and tiny spots of bleeding under the skin on both forearms and lower legs.
The girl again showed a number of abnormalities in blood tests, including immune cell abnormalities, and evidence of nerve damage in nerve-muscle tests.
Antibody tests returned positive for antinuclear antibodies (ANAs), which are common in SLE and other autoimmune conditions.
The patient was given conservative treatment with intravenous, into-the-vein, antibiotics. She experienced nose bleeding that led to administration of a blood transfusion. She also received intravenous steroids followed by intravenous immunoglobulin, an approach meant to block self-reactive antibodies in the blood. However, her symptoms persisted.
She went home without further treatment against medical advice.
Three days later, the girl arrived at the researchers’ hospital, where it was determined she met the criteria for an SLE diagnosis. This included the presence of ANAs, persistent fever, fluid in the lungs, low levels of immune cells and blood-clotting platelets, signs of red blood cell destruction, joint pain, and neurological problems.
The scientists then generated the COVID-19 vaccine using the Aivita kit and the girl’s own immune cells. A day after the vaccination, she experienced gradual pain reductions and motor function improvements.
A week later, she could move independently and walk without any aids. Laboratory findings supported this clinical improvement, with normalization of blood parameters.
She remained stable after a month — without additional SLE treatments — with disease activity scores reflecting no active disease. She had a minor relapse, swelling and pain of the joints, after three months which was resolved with ibuprofen.
Importance of boosting immune-tolerating properties of DCs
Researchers believe the ability for the vaccine to ease SLE manifestations is not necessarily linked to its COVID-19-fighting abilities, but rather, an ability to boost DCs’ tolerogenic responses to ease autoimmunity.
Indeed, preclinical research has indicated that boosting the immune-tolerating properties of DCs could help ease SLE symptoms.
The concept of using DC immunotherapy to treat autoimmune diseases has existed for a while, with clinical trials testing this approach in people with rheumatoid arthritis, type 1 diabetes, or multiple sclerosis.
“However, no results of clinical trials of DC immunotherapy on SLE have been published,” the researchers wrote.
“DC immunotherapies are potentially effective for autoimmune patients and have good safety,” the team wrote. “However, the efficacy of the use of this therapy in SLE still requires further research.”
