What is Rheumatoid Arthritis?
Rheumatoid arthritis is a chronic autoimmune disease which presents with symptoms of inflammation and pain in the joints. This disease affects the whole body with symptoms ranging from mild to severe. Rheumatoid arthritis causes joint pain, swelling, stiffness, and loss of function in both arms or legs of the same joint.
The exact cause of rheumatoid arthritis is not known. However, certain factors have been implicated in increasing the risk of developing or precipitating its onset. Factors that may trigger the onset of rheumatoid arthritis include:
- Exposure to dust in the air such as silica and asbestos, air pollution, insecticides and cigarette smoke.
- Obesity
- Trauma or physical injuries, such as bone fracture or breakage, joint dislocation or ligament damage
- Exposure to certain types of bacteria, such as bacteria associated with periodontal disease
- Having a history of viral infections such as infection with Epstein-Barr virus (EBV) which causes infectious mononucleosis.
- Two-thirds of people with rheumatoid arthritis are obese or overweight. Fat releases cytokines, a chemical mediator which are released into joints
Factors that increase the risk include having a family history of rheumatoid arthritis. Also, women are more likely to develop this disease than men.
What is Huntington’s Disease?
Huntington’s disease is an inheritable progressive disease that causes breakdown and degeneration of nerve cells in the brain. Huntington’s disease affects a person’s personalities and functional abilities resulting in a deficit in movement, cognition, and emotion.
Huntington’s disease is a genetic disorder, caused by an inherited defect in a single gene. This means that a person needs only one copy of the defective gene to develop the disease. A parent with a faulty gene could pass along the defective copy of the gene or the healthy copy to its offspring. This gives each child in the family, a 50 percent chance of inheriting the gene that causes the disease.
Individuals who possess 27 to 35 CAG repeats in the HTT gene do not develop Huntington disease, but they are at high risk of having offspring who will develop the disorder. As the gene is passed from parent to child, the size of the CAG trinucleotide repeat may elongate into the range associated with Huntington disease (36 repeats or more).
One might wonder, what do a terminal brain disease and a painful autoimmune condition have in common?
Scientists working at the University of California San Diego (USCD) School of Medicine and Icahn School of Medicine at Mount Sinai in New York have discovered an apparent epigenetic overlap between the origins of Huntington’s disease and rheumatoid arthritis, an extraordinary finding that could potentially open the door for new discoveries and therapeutics targeting both diseases.
“We did not expect to find an overlap between rheumatoid arthritis and Huntington’s disease, but discovering the unexpected was the reason that we developed this technology. Now that we have uncovered this connection, we hope that it opens a door for treatment options for people living with either disease,” said Firestein, the senior author
The study “Comprehensive epigenetic landscape of rheumatoid arthritis fibroblast-like synoviocytes” was published in the journal Nature Communications.
The investigative approach used by Dr. Firestein and his research team involved developing a unique algorithm, or set of computational rules, called EpiSig, which integrated and reduced the number of epigenetic combinations in the genes of patients with rheumatoid arthritis. The team could then identify new cell signaling pathway. EpiSig’s analysis showed them all of the epigenetic combinations found in the genes of people with rheumatoid arthritis, presenting new signaling pathways and connections to Huntington’s disease. The study was not without its challenges
“Comparing different types of epigenomic data is difficult because it involves a variety of different data subsets that cannot normally be analyzed together, including various methods in which DNA gets modified,” said Dr. Wei Wang, Professor of chemistry, biochemistry and cellular and molecular medicine at UC San Diego School of Medicine.
Epigenetics, or “above the genome,” is the study of processes that alter the gene structure without changing the DNA sequence itself. These DNA modifications are vital to human growth and development and change throughout people’s lives. Epigenetic changes are influenced by a variety of external factors, including stress, physical activity, and lifestyle choices.
“By revealing the comprehensive epigenetics behind RA, we now have a better understanding of this disease. More importantly, our new approach could not only help patients with RA but also people with other immune-mediated diseases,” Dr. Firestein concluded.
What are the Early Signs of Huntington’s Disease?
Huntington’s disease causes a wide range of signs and symptoms. Which symptoms come first differs greatly among affected individuals. There are three groups of disorders in Huntington’s disease: movement, cognitive and psychiatric disorders. Some of this disorder may never appear, while others appear to be more dominant.
Movement Disorders
In the early stages of Huntington’s disease, the patient is likely to experience mild twitching of the fingers, toes, face or the limbs. These are also prone to falling or knocking things over due to an impaired gait, posture, and balance.
The most physically recognizable symptom is chorea, which is an uncontrollable dance-like or jerking movements. These movements start as small twitches and gradually deteriorates over a period of years. A few percentages of people with HD will not experience chorea.
Cognitive Disorders
People with HD express difficulties in processing thought or finding words. They find it difficult organizing, prioritizing or focusing on tasks. Their lack of impulse control can result in outburst, causing them to act without thinking.
Psychiatric Disorders
Signs and symptoms include:
- Difficulty sleeping
- Frequent thoughts of death or suicide
- Fatigue and loss of energy
- Elevated mood, overactivity, impulse behavior
- Alternating periods of depression and mania
References
Ai, R., Laragione, T., Hammaker, D., Boyle, D., Wildberg, A., & Maeshima, K. et al. (2018). The comprehensive epigenetic landscape of rheumatoid arthritis fibroblast-like synoviocytes. Nature Communications, 9(1). doi: 10.1038/s41467-018-04310-9
Barden, J., Mullinax, F., & Waller, M. (1967). Immunoglobulin levels in rheumatoid arthritis: Comparison with rheumatoid factor titers, clinical stage, and disease duration. Arthritis & Rheumatism, 10(3), 228-234. doi: 10.1002/art.1780100308
Doody, K., Bottini, N., & Firestein, G. (2017). Epigenetic alterations in rheumatoid arthritis fibroblast-like synoviocytes. Epigenomics, 9(4), 479-492. doi: 10.2217/epi-2016-0151
The link between bacterial infections and reduced risk of rheumatoid arthritis. (2015). Nursing Standard, 29(25), 16-16. doi: 10.7748/ns.29.25.16.s21
Vonsattel, J. (2007). Huntington disease models and human neuropathology: similarities and differences. Acta Neuropathologica, 115(1), 55-69. doi: 10.1007/s00401-007-0306-6
