Hematopoietic Stem Cell Transplantation in Autoimmune Diseases

Introduction:

Autoimmune diseases are considered to be a major cause of the burden on people’s lives and the healthcare system as a whole. The conventional way to manage such autoimmune diseases is to streamline the immune response in the affected individuals. However, in recent days, regenerative medicine has played a significant role in managing autoimmune diseases.

What Are the Limitations of Conventional Treatment of Autoimmune Diseases?

The main reason for the incidence of autoimmune disease is a dysfunctional immune system, where a person’s immune system identifies the body's cells as foreign agents (antigens) and attacks them to get rid of them. This is achieved by synthesizing antibodies in the body. This process causes intense inflammation within the body and damages cells and tissues. Thus, the main management modality of such autoimmune diseases is to modify the response produced by the body and curb the inflammatory process. There are several limitations to this approach.

• Traditional methods tend to provide only transient relief to the autoimmune disorder symptoms rather than permanent relief.

• Corticosteroids used in the treatment can increase the incidence of attack by infectious agents.

• Disturbance to the gastrointestinal tract is very common after taking conventional therapy.

• On long-term usage of these drugs, organ damage becomes an obvious side effect.

• The most important of all the limitations is that not all people experience relief from conventional therapy administration. Many patients require alternate therapy for symptom relief.

What Is Hematopoietic Stem Cell Transplantation in Autoimmune Disease?

To overcome the limitations of such conventional therapies, the approach to treating autoimmune diseases was shifted. The focus and goal was to target the etiological agent—the dysfunctional immune response in the body. To achieve this, hematopoietic stem cell transplantation was introduced because this treatment has the potential to have a more profound and lasting impact by resetting the immune system to a state of tolerance.

Process of Transplantation:

• Chemotherapy or radiotherapy will be subjected to the patient to ablate the defective immune cells from the immune system.

• After physical and clinical examination, patients are subjected to a process called apheresis, in which blood cells with the capacity to differentiate (stem cells) are removed from bone marrow or the peripheral blood. This process ensures that only hematopoietic stem cells are extracted and that other cellular hematological components are returned to circulation.

• Once the immune system clears any abnormal cells, these extracted hematopoietic stem cells will be reintroduced into the patient’s body circulation. These stem cells reach the bone marrow, differentiating and multiplying to form necessary blood cells. Over time, the transplanted stem cells engraft in the bone marrow and reconstitute the immune system.

The entire process, from chemotherapy to achieving optimal immune response in the body, may take several weeks to months.

How Does Hematopoietic Stem Cell Transplantation Work in Autoimmune Disorders?

• Hematopoietic stem cell transplantation tends to reset the entire defective immune system, a pathologic factor in autoimmune diseases. This is achieved by first depleting the existing immune cells through a conditioning regimen, typically involving chemotherapy and sometimes radiation. This process eliminates the autoreactive immune cells responsible for the autoimmune response.

• Immune cells regenerate only after the transplanted hematopoietic cells repopulate. This ensures that normal-functioning immune cells are produced in the body.

• Immune reconstitution occurs after transplanting hematopoietic stem cells. Thus, a balanced immune system is formed in the body, where immune cells can differentiate the body’s and foreign cells.

• Hematopoietic stem cell transplantation may also induce immune tolerance, wherein the immune system becomes tolerant to self-antigens and less likely to mount an autoimmune attack. This tolerance induction is facilitated by regenerating the immune system in a controlled environment.

When all these altered immune responses are reconstituted, the inflammatory processes in the body are also curbed. This can lead to clinical improvement and, in some cases, long-term remission of autoimmune symptoms.

What Are the Autoimmune Disorders Treated With Hematopoietic Stem Cell Transplantation?

• Studies have shown that patients with multiple sclerosis have shown remission with disability improvement after hematopoietic stem cell transplantation.

• Benefits were also seen in patients with advanced systemic sclerosis, and skin involvement was also reduced.

• The joint damage was halted in rheumatoid arthritis patients after hematopoietic stem cell transplantation.

Noticeable results were also noted in systemic lupus erythematosus and type I diabetes mellitus patients.

What Are the Limitations of Hematopoietic Stem Cell Transplantation in Autoimmune Diseases?

• The therapy used to reset the immune system itself can cause toxicity. Chemotherapy and radiotherapy can induce a significant amount of damage to the body's cells. They can also cause adverse effects like profuse vomiting, headache, hair loss, loss of body weight, and organ toxicity, such as liver or kidney toxicity.

• Following the hematopoietic stem cell transplantation procedure, patients have been reported with an increased incidence of infectious diseases. This is because the immune system becomes extremely weak by the time new immune cells regenerate. Serious infections should be treated with antibiotics, especially through administering parenteral (drugs other than the oral route).

• Hematopoietic stem cell transplantation is also performed after receiving a graft from the donor. In such cases, a graft-versus-host reaction is initiated in the recipient’s body, further exacerbating the severity of the existing autoimmune condition.

• While HSCT can induce remission or even cure in some patients, there is a risk of disease relapse following transplantation. Inadequate immune reconstitution, persistence of autoreactive immune cells, or incomplete elimination of the underlying autoimmune pathology may contribute to disease recurrence.

• On a long-term basis, hematopoietic stem cell transplantation is known to cause fertility issues, hormonal imbalance in the body, chronic graft dysfunction, and incidence of secondary malignancies.

• The complete process (initiation of chemotherapy, grafting, and transplantation) is time-consuming and requires extensive medical expertise. The availability of such transplant centers could be much higher.

Conclusion:

Nevertheless, the field of hematopoietic stem cell transplantation in autoimmune disease treatment is evolving. Further research is focused on optimizing the right protocol for the process and harnessing the full potential of this transplantation for managing autoimmune diseases.