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Do Infections Trigger the Development of Rheumatoid Arthritis?

Posted on February 14, 2022
Medically reviewed by
Ariel D. Teitel, M.D., M.B.A.
Article written by
Kristopher Bunting, M.D.

Rheumatoid arthritis (RA) is an autoimmune inflammatory arthritis that affects about 1 percent to 2 percent of people worldwide, causing pain, inflammation, and damage to the joints. In some people, the condition can harm a variety of other systems, including the skin, eyes, lungs, heart, and blood vessels. The causes of RA are not fully understood but appear to be due to a combination of genetic predisposition and environmental factors, including infections.

The right combination of genetic risk factors and infection with certain viruses or bacteria may lead to the development of RA.

What Infections Have Been Linked to RA?

Autoimmune diseases occur when the body’s immune system attacks healthy tissue as if it were an infection. In some cases, a normal immune response to certain bacteria and viruses can trigger an autoimmune reaction.

Scientists have tried to identify infections that lead to RA, but the process of autoimmunity is complex. Because certain infections tend to be very common, and because only a small percentage of people develop RA after becoming infected, the connection between infection and RA is still uncertain. Not everyone develops RA after specific infections, so it is hard to pinpoint exactly which infectious organisms may contribute to this autoimmune disease.

Several different bacterial infections and viral infections have been suspected of increasing the risk of RA in some people.

Bacterial Infections

Some of the most promising connections between bacterial infection and RA are related to bacteria that cause gingivitis (gum disease). Both Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans are linked to increased RA risk.

It is believed that enzymes carried by both of these bacteria contribute to autoimmunity, resulting in increased anti-cyclic citrullinated peptide (anti-CCP) antibodies, which is a diagnostic marker of RA along with rheumatoid factor.

Other bacteria are also suspected to cause RA in some people, including:

Viral Infections

Epstein-Barr virus (EBV) is an extremely common virus that causes a type of infectious mononucleosis (“mono”), sometimes called the “kissing disease.” EBV has been linked to many chronic medical conditions. In addition to autoimmune diseases — such as RA, Sjögren's syndrome, and systemic lupus erythematosus — EBV is also linked to certain types of cancer.

Most people are exposed to EBV at some point in their lives, and the virus affects more than 90 percent of people worldwide. EBV can infect immune cells (B cells) and remain there throughout a person’s life. EBV can reactivate B cells, sometimes resulting in the production of autoantibodies — antibodies that target and attack healthy tissue.

Other viruses suspected to cause RA in some people include:

How Can Infections Increase the Risk of RA?

One way that the immune system fights infection is by producing antibodies against bacteria and viruses. When the immune system recognizes a foreign bacteria or virus, the immune system creates antibodies against proteins found in those disease-causing microorganisms.

Not all antibodies are effective for fighting infection, so the immune system makes many attempts to find an antibody that works. Sometimes, these foreign proteins are extremely similar to normal, healthy proteins, which can allow the antibodies to mistakenly attack healthy tissue through processes called molecular mimicry and epitope spreading.

Other infections such as EBV can result in proliferation, or cloning, of B cells that produce antibodies. EBV can infect B cells and lead to continued production of antibodies that attack healthy tissue that would otherwise not persist over time.

What Does This Mean for People With RA?

RA is a common debilitating disease and is the subject of ongoing research. Although science does not yet have a complete understanding of how RA develops, new answers are being uncovered every day.

Understanding what causes RA and how infection may contribute to its development can lead to better treatments and help identify people who could benefit from early screening for RA and other rheumatic diseases. Early screening may allow for early interventions to control disease activity and prevent progression.

If you have had one of these infections before developing RA symptoms, it may be worthwhile to mention this piece of your medical history to your rheumatologist or other health care provider treating your RA. Research into how infections may trigger RA development always needs more data. Even if the information is simply added to your medical chart, it may help researchers in the future identify the potential role of your infection in the development of RA.

Talk With Others Who Understand

On myRAteam, the social network for people with rheumatoid arthritis, more than 176,000 members come together to ask questions, give advice, and share their experiences with others who understand life with RA.

Do you think one of these infections may have contributed to your RA? Share your thoughts and experience in the comments below, or start a conversation by posting on your Activities page.

References
  1. Rheumatoid Arthritis — Mayo Clinic
  2. Microbial Infection and Rheumatoid Arthritis — Journal of Clinical and Cellular Immunology
  3. The HLA System: Genetics, Immunology, Clinical Testing, and Clinical Implications — Yonsei Medical Journal
  4. HLA-DRB1 Gene — MedlinePlus
  5. How Rheumatoid Arthritis Can Result From Provocation of the Immune System by Microorganisms and Viruses — Frontiers in Microbiology
  6. Epstein-Barr Virus and Infectious Mononucleosis — Centers for Disease Control and Prevention
  7. Should Infection Still Be Considered as the Most Likely Triggering Factor for Rheumatoid Arthritis? — Annals of the Rheumatic Diseases
  8. Porphyromonas Gingivalis Facilitates the Development and Progression of Destructive Arthritis Through Its Unique Bacterial Peptidylarginine Deiminase (PAD) — PLoS Pathogens
  9. Aggregatibacter Actinomycetemcomitans-Induced Hypercitrullination Links Periodontal Infection to Autoimmunity in Rheumatoid Arthritis — Science Translational Medicine
  10. Anti-CCP Antibody, a Marker for the Early Detection of Rheumatoid Arthritis — Annals of the New York Academy of Sciences
  11. Rheumatoid Factor — StatPearls
  12. Role of Infections in the Pathogenesis of Rheumatoid Arthritis: Focus on Mycobacteria — Microorganisms
  13. Increased Risk of Rheumatoid Arthritis Among Patients With Mycoplasma Pneumonia: A Nationwide Population-Based Cohort Study in Taiwan — PLoS One
  14. Rheumatoid Arthritis Is Caused by a Proteus Urinary Tract Infection — APMIS
  15. Distinct Bacterial Colonization Patterns of Escherichia Coli Subtypes Associate With Rheumatoid Factor Status in Early Inflammatory Arthritis — Rheumatology
  16. Epstein–Barr Virus and Rheumatoid Arthritis: Is There a Link? — Arthritis Research & Therapy
  17. Epstein–Barr Virus Epidemiology, Serology, and Genetic Variability of LMP-1 Oncogene Among Healthy Population: An Update — Frontiers in Oncology
  18. HTLV-1 Infection and Rheumatic Diseases — Frontiers in Microbiology
  19. Human Retrovirus-5 in Rheumatic Disease — Journal of Autoimmunity
  20. Rheumatoid Arthritis After Human Parvovirus B19 Infection — Annals of the Rheumatic Diseases
  21. Respiratory Viral Infections and the Risk of Rheumatoid Arthritis — Arthritis Research & Therapy
All updates must be accompanied by text or a picture.
Ariel D. Teitel, M.D., M.B.A. is the clinical associate professor of medicine at the NYU Langone Medical Center in New York. Review provided by VeriMed Healthcare Network. Learn more about him here.
Kristopher Bunting, M.D. studied chemistry and life sciences at the U.S. Military Academy, West Point, and received his doctor of medicine degree from Tulane University. Learn more about him here.

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