# data[].attributes.attachment_caption
What is Rheumatoid Arthritis? | RA Awareness Day 2017

# data[].attributes.body
Rheumatoid arthritis is an autoimmune and inflammatory disease in which your immune system mistakenly attacks healthy cells in your body, producing inflammation (painful swelling) in the afflicted areas. Rheumatoid arthritis primarily affects the joints, often attacking multiple joints at once.

Centers for Disease Control and Prevention. (2020, July 27). Rheumatoid Arthritis (RA) | Arthritis | CDC. Www.cdc.gov. https://www.cdc.gov/arthritis/basics/rheumatoid-arthritis.html#:~:text=Rheumatoid%20arthritis%2C%20or%20RA%2C%20is

What is Rheumatoid Arthritis? | RA Awareness Day 2017. (n.d.). Www.youtube.com. Retrieved October 10, 2023, from https://youtu.be/RauJmjLH-hQ?si=-vWvOasL_vDFdjaf

# data[].attributes.attachment_link.title
What is Rheumatoid Arthritis? | RA Awareness Day 2017

# data[].attributes.body
In Rheumatoid Arthritis (RA), immune cells mistakenly attack tissues lining the joints, leading to stiffness, pain, and disability.  RA involves complex interactions between immune cells in the joints responsible for normal tissue maintenance. It is a chronic autoimmune disease initiated by CD4+ helper T cells that promote inflammation. A type of immune cell called macrophages cues fibroblasts to destroy joint tissue through a growth factor called HB-EGF and blocking the receptor for the growth factor called EGFR. This leads to osteoclast generation resulting in bone deconstruction which is the hallmark of RA (Rogers, pp 1457).

NIH Research Matters (2019). Understanding rheumatoid arthritis at the cellular level, NIH.gov. https://www.nih.gov/news-events/nih-research-matters/understanding-rheumatoid-arthritis-cellular-level#:~:text=In%20rheumatoid%20arthritis%20(RA)%2C,the%20disease%20in%20some%20people.

Rogers, J. (2024). McCance & Huether’s pathophysiology: the biologic basis for disease in adults and children. p.1457 (9th ed). Elsevier

# data[].attributes.attachment_link.readable_text
At a Glance

Researchers identified ways that immune cells and joint cells interact to produce the inflammation and tissue damage seen in rheumatoid arthritis.

Understanding these interactions at the single-cell level could help scientists develop more personalized treatments for the disease.

In rheumatoid arthritis (RA), immune cells mistakenly attack tissues lining the joints. This can lead to stiffness, swelling, pain, and disability.

More than a million people nationwide live with RA. Existing drugs can slow the progression of the disease in some people. But they don't work for everyone and can stop working in others over time.

The exact cause of RA isn't known. It involves complex interactions between immune cells and the cells in the joints responsible for normal tissue maintenance. A better understanding of these interactions could help scientists develop new drugs that work for more patients.

A large-scale collaboration among government, industry, and nonprofit organizations called the Accelerating Medicines Partnership (AMP) focuses on gene expression and signaling in tissues where disease is active, such as the joints of people with RA. AMP investigators led by Drs. Soumya Raychaudhuri and Michael Brenner at Brigham and Women's Hospital, Jennifer Anolik at the University of Rochester, and Laura Donlin at the Hospital for Special Surgery in New York examined synovium-the thin tissue that lines joints-to understand interactions at the single-cell level and find potential targets for treatment. They analyzed tissue collected by AMP investigators from 36 people with RA and 15 others with osteoarthritis for comparison.

The team used advanced laboratory techniques to examine gene expression patterns in single cells from groups of specific types of immune and joint cells. The work was funded by NIH's National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and others. Results were published in Nature Immunology on May 6, 2019.

The researchers identified 18 unique cell populations in the joints based on gene expression patterns. Some of the cell types were seen in large numbers in samples from people with RA. These included both certain immune cells and other cells like fibroblasts, which build connective tissue in the joints. The team was also able to trace which specific cell types produced several molecules that promote inflammation in RA. Future work will be needed to understand the roles of these cells in RA and other immune diseases.

Donlin's team focused on a type of immune cell called macrophages. In tissue samples grown in the lab, a subset of macrophages cued fibroblasts to destroy joint tissue through a growth factor called HB-EGF. Blocking the receptor for HB-EGF, known as EGFR, with an experimental anti-cancer drug shut down this destructive process. These findings were published in Science Translational Medicine on May 8, 2019.

The drug used in these experiments may be too toxic to use in people with RA. However, these results show that the disease could potentially be treated by methods other than suppressing the immune system, which is the basis for most current RA therapies. Other experiments using the tissues provided new insights into how drugs currently used to treat RA work at the cellular level.

"Our work...has identified previously unknown subsets of cells and provided new insights about how some of these cell types interact with each other to drive RA," Donlin says. "We hope that through a better understanding of the cell populations in individual patients we can provide a means by which we can treat them with precision medicine strategies at the earliest stages of disease."

# data[].attributes.attachment_link.keywords[]
accelerating medicines partnership rheumatoid arthritis and systemic lupus erythematosus

# data[].attributes.attachment_link.keywords[]
epidermal growth factor receptor inhibitor

# data[].attributes.attachment_link.title
Understanding rheumatoid arthritis at the cellular level

# data[].attributes.attachment_link.description
Researchers identified ways that immune cells and joint cells interact to produce the inflammation and tissue damage seen in rheumatoid arthritis.

# data[].attributes.body
Inflammation (in this case, swelling and pain manifestations, less so redness and heat) surrounds the affected tissue, which results in an initial thickening of the synovial membrane. Angiogenesis occurs to compensate for the injured synovium and to bring more proinflammatory cytokines to the area. The massive release of cytokines, chemokines, and other immune cells may also lead to an invasive phenotype of RA. The result is bone erosions and loss of cartilage at the joint site. Rheumatoid nodules are common in peri-articular areas, due to the necrosis of the collagen. Joint movement becomes limited with progression.

Chauhan K, Jandu JS, Brent LH, et al. (2023) Rheumatoid Arthritis. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK441999/

# data[].attributes.headline
Whether this condition conforms to the traditional definition of the hypersensitivity type 3

# data[].attributes.subject
Whether this condition conforms to the traditional definition of the hypersensitivity type 3

# data[].attributes.body
In type III hypersensitivity reaction antibodies bind to circulating antigens leading immune complexes to be deposited into vascular tissue. RA causes inflammation of the joints. 70 % of patients with RA make rheumatoid factor, which is an IgM anti-IgG antibody. RA does conform to the traditional definition of a type III hypersensitivity reaction since it involves inflammation of body tissue in the joints causing arthritis.

Rogers, J. L. (2022). McCance & Heuther’s Pathophysiology: The Biologic Basis for Disease in Adults and Children. (9th ed., pp. 259-260). Elsevier.

University of Hawaii (n.d.). Immunopathology - The Hypersensitivities. http://www2.hawaii.edu/~johnb/micro/micro161/immunopath_chap15and16/Chapter15,16-Ab,%20cell%20hyp.htm

# data[].attributes.body
Risk factors for rheumatoid arthritis include:
1. Age:  Rheumatoid arthritis can strike at any age, although it is more likely to occur as people get older.
2. Gender:  Women have rheumatoid arthritis more frequently than males. Researchers believe that for certain women, reproductive and hormonal variables may contribute to the disease's development.
3. Smoking:  Individuals who smoke regularly run a higher chance of developing rheumatoid arthritis. Smokers may experience a more severe case of the illness.
4. Family history and genetics: There is a higher risk of developing RA if a family member has the condition. The chance of developing RA is slightly increased by a number of hereditary variables.
5. Obesity: Being obese may both raise the likelihood of developing the condition and restrict how much it can be treated.

NIAMS. (2017). Rheumatoid Arthritis. National Institute of Arthritis and Musculoskeletal and Skin Diseases. https://www.niams.nih.gov/health-topics/rheumatoid-arthritis

Risk factors for developing rheumatoid arthritis. (n.d.). InviTRA. Retrieved October 10, 2023, from https://www.invitra.com/en/can-i-get-pregnant-if-i-am-diagnosed-with-rheumatoid-arthritis/rheumatoid-arthritis-risk-factors/

# data[].attributes.attachment_caption
Joints that are commonly impacted by rheumatoid arthritis (Rheumatoid Arthritis: Overview, 2016)

# data[].attributes.body
Rheumatoid arthritis affects various joints in different persons, and the symptoms varies as well. They will be determined by the severity of the inflammation and the extent of the rheumatoid arthritis.
Rheumatoid arthritis frequently manifests as:
1. Painful, swollen, and warm joints
2. Stiff joints
3. Weakness: Because painful, stiff joints are frequently not used as much, the muscles might gradually get weaker.
4. Exhaustion: Because rheumatoid arthritis affects the entire body, it frequently results in generalized physical weakness and fatigue.
5. Rheumatoid nodules: As the condition worsens, little, hard lumps beneath the skin known as rheumatoid nodules might appear. Typically, they are not responsive to touch or pressure.

Commonly, the same joints on both sides of the body are affected by the inflammation.

Rheumatoid arthritis: Overview. (2016, August 11). Nih.gov; Institute for Quality and Efficiency in Health Care (IQWiG). https://www.ncbi.nlm.nih.gov/books/NBK384455/

# data[].attributes.body
There is no cure for RA. Thus, the key to treating RA is treating it early, so that lighter medications and lower dosages may be used. The more late-stage the disease is, the more aggressive the treatment and medications are to reduce the inflammation, which comes with serious side effects.
For medication, treatment typically begins with NSAIDs and keeping an active lifestyle. Walking and yoga can greatly reduce inflammation while keeping joints flexible.
Corticosteroids are the next plan of action as they work to suppress the immune system but come with greater risks. Longer term drugs, speficially antirheumatic drugs, work by stopping the immune system, but with side effects of liver damage and risk for increased infection. In severe cases, joint replacement surgery may be needed.

Ezerioha, M, MD. (2018). RA Treatment: What is the Safest Treatment for Rheumatoid Arthritis? Rheumatoid Arthritis Support Network. RA Treatment: What is the Safest Treatment for Rheumatoid Arthritis? - RheumatoidArthritis.org