In this article, I briefly describe the methods of treatment for autoimmune diseases.
Autoimmunity and its causes
The immune responses of an organism against its healthy cells and tissues give rise to a condition known as autoimmunity. It is the presence of antibodies and T lymphocytes against self-antigens. The diseases linked to autoimmunity are known as autoimmune diseases.
There are different factors responsible for the development of autoimmunity. They include genetic factors, environmental factors, or maybe the involvement of certain T helper cells. Genetically we all are quite similar, but sometimes a few small nucleotide differences at the MHC locus bring the problem. Two individuals with the exactly same set of MHC alleles can develop autoimmune diseases. The other non-MHC immune genes are also linked with autoimmune diseases.
The different factors linked with autoimmunity
Other than genetics related to immunity, sex also plays a role in the development of autoimmunity. According to some research studies, women are more prone to autoimmune diseases than their male counterparts. The state of enhanced immunity in women makes them more prone to infections and infectious diseases. Sex hormones also play a vital role in the observed difference in autoimmunity rates between men and women. In the disease systemic lupus erythematosus (SLE), young women at the age of childbirth are more prone as lupus is high due to the elevated estrogen state during pregnancy.
Environmental factors are also held responsible for the development of autoimmunity. It is observed that autoimmune disorders are more common in certain specific geographic locations or in particular climates. Certain gut microbes communicate with immune cells in the intestinal mucosa or elsewhere in the body and this interaction does not remain local, which helps to suppress autoimmune diseases in distant locales. Sometimes, infections also help to induce autoimmunity in individuals.
Many research studies indicate that autoreactive TH1 cells and cytokine IFN-γ supports autoimmunity. Later it has observed that TH17 cells and the cytokines IL-17 and IL-23 produced by them are linked to various autoimmune diseases.
The treatment for autoimmunity
To treat autoimmune diseases, current therapies can be grouped into three categories, such as broad-spectrum immunosuppressive treatments, immunosuppression directed at specific cells or pathways, and targeted immunotherapy.
Broad-spectrum immunosuppressive treatments
Broad-spectrum therapies are the first-generation therapies for the treatment of autoimmune diseases. These therapies do not completely cure the disease. However, they suppress the symptoms, which allows the patients to lead a normal life. Some of the anti-inflammatory drugs are corticosteroids, azathioprine, cyclophosphamide, and methotrexate, which suppress lymphocytes by inhibiting their proliferation or by killing rapidly dividing leukocytes. These treatments can inhibit inflammation, but have some marked long-lasting side effects. The side-effects include general cytotoxicity to all rapidly dividing cells, an increased risk of uncontrolled infection, and sometimes even the development of cancer.
Some autoimmune diseases need the removal of a specific organ or set of toxic compounds. This will help mitigate the symptoms. Patients suffering from the autoimmune disease myasthenia gravis, often experience thymic abnormalities. If a patient undergoes a thymectomy, it can increase the chance of remission. In another method, the removal of the patient’s plasma antibodies, also known as plasmapheresis, helps in eliminating autoreactive antibodies with the immune complexes.
Immunosuppression directed at specific cells
Strategies to kill or block B cells help to provide benefits for the patients. A monoclonal antibody against the B cell-specific antigen CD20 aids in decreasing a subset of B cells and provides temporary relief for patients suffering from rheumatoid arthritis. However, the strategies applied to treat autoimmune disorders need to target T cells as these are pathogenic or helpful to autoreactive B cells.
The first use of anti-T-cell antibodies in autoimmunity targeted the CD3 molecule. These were structured to deplete T cells without signaling through this receptor. This method worked to some extent in treating type-1 diabetes. However, it induced broad-spectrum immune suppression. In some animal models, the application of more specific anti-CD4 antibodies for the diseases of multiple sclerosis and arthritis proved to be beneficial. However, for human beings, this method has not shown any effectiveness. In many mouse models of autoimmunity, the transfer of TREG cells or T regulatory cells can alleviate disease symptoms. However, translating this from mice to humans is difficult. This is because selecting a population of TREG cells proves to be an onerous task.
Blocking specific steps in autoimmune inflammatory processes
Targeting specific steps in the inflammatory process does protect us from foreign invaders. Drugs that block TNF- α, one of the early mediators in many autoimmune inflammatory processes, are used in the treatment of autoimmune diseases like rheumatoid arthritis, psoriasis, and Crohn’s disease. Other anti-inflammatory treatments for autoimmunity include targeting the IL-2 receptor, IL-1, and IFNs. These treatments are expensive and have side effects as well.
The class of drugs used by millions of people for lowering cholesterol known as statins has been found to lower serum levels of C-reactive protein. The C-reactive protein (CRP) is an acute-phase protein, which is an indicator of inflammation. When the level of CRP is reduced, it can inhibit pro-inflammatory cytokines and decrease the expression of adhesion molecules on endothelial cells. The lowering of expression of adhesion molecules on endothelial cells reduces many symptoms of most autoimmune diseases. Clinical trials of statins for the treatment of autoimmune diseases like rheumatoid arthritis (RA) and multiple sclerosis have shown inspiring results.
The lymphocyte movement into sites of inflammation is controlled by signals from chemokines. The compounds block these chemokines and can foil autoimmune processes. A compound known as natalizumab, a monoclonal antibody specific for the adhesion molecule α4 integrin, has been permitted for the treatment of multiple sclerosis. The compound is involved in lymphocyte homing to the brain. However, natalizumab has its side effects too. Nearly five hundred patients treated for more than two years have developed a serious CNS (central nervous system) infection. The side effect is developed from enhanced modification and infection of B cells fostering the JC virus, which is the causative organism of brain infection.
Immunotherapies interfering co-stimulation
T cells need two signals to completely activate themselves. The first signal is through the T-cell receptor (TCR), and the second signal is the co-stimulation signal, which helps to fully activate the T cells. Without the co-stimulation signal, T cells go through apoptosis. They become anergic or are selected as regulatory T cells to become specific immune inhibitors. Thus, activation of T cells can be controlled by blocking co-stimulation of them. CTLA-4 binds with CD80/86 with twenty times more affinity than CD28, thus blocking the co-stimulation of T cells.
A fusion protein was generated by combining the extracellular domain of CTLA-4 and the human IgG1 constant region, called CTLA-4Ig. This fusion protein is used as a therapeutic drug, Abatacept for treating rheumatoid arthritis. This drug is designed to block CD80/86 on antigen-presenting cells (APCs) from engaging with CD28 on T cells. However, it does not have the same outcomes for other autoimmune diseases. This drug has limited success with the disease multiple sclerosis and shows disappointing results in the treatment of SLE (Systemic Lupus Erythematosus).
Targeted immunotherapy- antigen-specific
Antigen-specific immunotherapy precisely targets only the autoreactive cells sparing all other leukocytes. The antigen-specific tolerance is manipulated by introducing the specific antigen in a tolerogenic form. However, in autoimmune diseases like type-1 diabetes and multiple sclerosis, even a well-characterized self-antigen in a tolerogenic form, carries the risk of worsening the disease.
The research for targeted immunotherapy is still ongoing, and many compounds that act as immunotherapy treatments for autoimmune disorders are in their earliest stages of development. For the treatment of type-1 diabetes, Francisco Quintana and coworkers are traversing a novel immunotherapy approach. They are using nanoparticles coated with a target antigen proinsulin and a molecule that can deliver a tolerogenic signal to antigen-presenting cells. Treatment of murine dendritic cells with these nanoparticles induced a tolerogenic phenotype in vitro.
Along with inducing a tolerogenic phenotype, it suppressed proinflammatory cytokine production, leading to T-cell differentiation into a regulatory phenotype. When they administrated these coated nanoparticles to NOD mice (experimental animals), it blocked the unprompted development of diabetes. If this strategy can be successfully applied to humans, then, a new hope will emerge for antigen-specific immunotherapy treating autoimmune diseases.
Conclusion
The treatment for autoimmunity can be grouped into three categories. They are broad-spectrum immunosuppressive treatments, immunosuppression directed at specific cells or pathways, and targeted immunotherapy. Broad-spectrum therapies do not completely cure the disease. However, they suppress the symptoms, which allows the patients to lead a normal life.
Immunosuppression targeted at specific cells involves targeting B cells and T cells. The first use of anti-T-cell antibodies in autoimmunity targeted the CD3 molecule. However, in treating type 1 diabetes, it induced broad-spectrum immune suppression. In many mouse models of autoimmunity, the transfer of TREG cells or T regulatory cells can alleviate disease symptoms. However, it is a tedious process.
Targeting specific steps in the inflammatory process protects us from foreign invaders. The cytokine TNF- α, one of the early mediators in many autoimmune inflammatory processes, is blocked by drugs treating autoimmune diseases. However, the method is expensive and has side effects as well.
In immunotherapies interfering with co-stimulation, activation of T cells is inhibited by blocking them. In antigen-specific targeted immunotherapy, the antigen-specific tolerance is manipulated by introducing the specific antigen in a tolerogenic form. The research for targeted immunotherapy is still ongoing, and many compounds that act as immunotherapy treatments for autoimmune disorders are in their earliest stages of development.
You may also like:
I, Swagatika Sahu (author of this website), have done my master’s in Biotechnology. I have around twelve years of experience in writing and believe that writing is a great way to share knowledge. I hope the articles on the website will help users in enhancing their intellect in Biotechnology.