Unraveling the network of autoimmune diseases

Seven years ago, Fatiha began to experience joint pain and hand swelling. Her doctor diagnosed her with her autoimmune disease, Sjogren’s Syndrome.

Three years later, the pain in the joints became severe, accompanied by a severe rash and sudden hair loss. The 32-year-old Fatiha, who asked to refrain from the name of his family, could hardly walk. His diagnosis was lupus, another autoimmune disease.

Lupus It causes inflammation of the skin, joints and kidneys. Symptoms include malaise, joint pain, skin rash, swelling of the lower extremities, and chest discomfort.

Even later, she received yet another diagnosis: rheumatoid arthritis.

Rheumatoid arthritis It occurs when the body’s immune system attacks the inner walls of joints, causing pain, inflammation, and ultimately cartilage and bone damage. This autoimmune disease can also harm the internal organs of the body, such as the heart, lungs, and nervous system.

Despite her illness, resident Tumble works in a restaurant and studies computer science at the University of Bridgeport. “I’ve never been ill in my life. Then one day everything changed,” she said.

What Causes Autoimmune Diseases?

Autoimmunity occurs when the immune system loses resistance to its own tissues and behaves as if it were infected with a pathogen. In addition, some researchers believe that autoimmunity can occur when the immune system invades the body and overreacts to pathogens that attack healthy tissues.

Autoimmune diseases are usually caused by mutations in multiple genes, but can be caused by environmental factors and stress. Inflammation is closely associated with autoimmune diseases. Most often it is a symptom of disability, but sometimes it is the trigger. “Immune diseases are very complex. You can have the wrong gene, Wrong microbial floraDiet, or environmental factors. ” Martin Kriegel, MD, PhDAssociate Professor of Immunobiology.

Find common ground between multiple autoimmune diseases

It is not uncommon for people who develop one autoimmune disease to experience one or more additional autoimmune diseases, as is the case with Fatiha. Understanding why this happens is difficult for clinicians and medical scientists. It is a net of intertwined cause and effect.

In 2015, a study of the Yale School of Medicine found that many autoimmune diseases are caused by changes in the enhancer component of DNA that can regulate several immune genes.Many affected Genes overlap between diseases..

Researchers believe that thymic dysfunction can cause multiple illnesses in some people, Kriegel said. The thymus helps the maturation of T lymphocytes (T cells), which are essential for fighting pathogens throughout the body. Sometimes, due to genetic defects, T cells are not taught how to distinguish between pathogens and normal cells.

In other cases, researchers suspect that defective checkpoints in the lymph nodes and spleen, where the immune response normally initiates, can lead to patients with multiple disorders.

Experts in this field combine the knowledge gained from the treatment of such patients with advances in laboratory research, not only to reassure countless people around the world, but also to help scientists with inflammation and the immune system. I believe it helps to better understand the basic mechanism.

Increasing general autoimmune diseases

The prevalence of autoimmunity is increasing in the United States. Researchers have found that over the past 25 years, ANA, an autoantibody for lupus erythematosus (self-targeting antibody), has increased by 44%, affecting 41 million people.

These autoantibodies are said to herald about 30% of people over 5-10 years with autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus (SLE), the most common types of autoimmune arthritis. .. Richard Bukara, MD, PhDWaldemar Von Zedtwitz, Professor of Medicine (Rheumatology) and Professor of Pathology and Epidemiology (Microbial Diseases) and Head of the Rheumatology, Allergy and Immunology section of the Yale School of Medicine.

“Fortunately, we can identify high-risk individuals and treatment may prevent the disease from progressing,” Bukara said.

How are autoimmune diseases treated?

Autoimmune diseases are usually treated with treatments that lower the immune system. This is an approach that makes patients vulnerable to viruses, bacteria, and other pathogens. “The immune system can be defensive or pathogenic. It’s a classic metaphor, a double-edged sword,” he said. Jordan Pover, MD ’77, PhD ’77Professor of Immunobiology, Professor of Translation Medicine and Pathology and Dermatology, Bayer.

Tumor necrosis factor (TNF) blockers are used to treat rheumatoid arthritis and other autoimmune diseases such as psoriatic arthritis, ulcerative colitis, and Crohn’s disease.But lupus and some
Other illnesses are not well understood. People with lupus are particularly likely to develop additional illnesses.

The need for precision medicine to treat autoimmune diseases

The causes and symptoms of autoimmune diseases are so complex that researchers have a hard time finding the best way to discuss them. Insoo Kang, MD, Associate Professor of Medicine (Rheumatology) at Yale School of Medicine describes the “rainbow spectrum” of disorders where cause and effect overlap. Often, some gene mutations are shared by multiple disorders.

in the meantime, Andrew Wan, MD, PhD, Associate Professor of Medicine (Rheumatoid Arthritis) and Immunobiology refers to the “constellation” of the disease. “We recognize that if we are honest with ourselves, we cannot treat all patients with complex inflammatory diseases together in the same way,” he said.

One of his patients, Royce Walters, a former post office worker in Hamden, Connecticut, was diagnosed with lupus more than 10 years ago, but her symptoms, such as fatigue, joint pain, and skin rash, It did not respond well to conventional treatments. For lupus.

After the king became her doctor four years ago, he tried another strategy. He realized that Walters was essentially suffering from her own personal lupus, so he got out of her traditional treatment and treated each of her symptoms separately. It’s working. “This is the best I’ve felt for a long time,” Walters said.

Wang believes that a new approach will be needed to address the complexity of autoimmune diseases. Today, many successful therapies target immune mediators. Immune mediators are signals that immune cells make to tell you that something is wrong with your body. He believes another approach is to target metabolic programs that support immune cells.

Wang said research progress is essential to deal with these complex illnesses, as do old-fashioned doctors.
It is important to listen to the patient as they will tell you what is wrong with them. “

Treatment of some autoimmune diseases has made remarkable progress, but doctors are dissatisfied with the slow progress of treatment for other diseases and the occurrence of multiple disorders and a collection of abnormal symptoms. .. For example, a patient diagnosed with a rare chronic autoimmune disease called antisynthase syndrome may require care in a variety of disciplines, from immunology to lungs and oncology.

“We need to understand the mechanism, especially the immune mechanism, but we also need to have a deeper understanding of what is happening to individual patients. It’s a kind of precision medicine,” Kang said. Said. “This is what we want to achieve in the next five to ten years.”

Originally released in the winter of 2020. Updated May 16, 2022.