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Is Spondylitis an Autoimmune Disease?

Posted on September 16, 2021
Medically reviewed by
Ariel D. Teitel, M.D., M.B.A.
Article written by
Kristopher Bunting, M.D.

Spondylitis is an umbrella term that refers to a spectrum of related diseases also known as spondyloarthritis or collectively called spondyloarthropathies. Spondylitis is an autoimmune and inflammatory arthritis that primarily affects the neck and spine. It can also involve the hips, eyes, bowels, tendons, and other joints.

What Is an Autoimmune Disease?

When the immune system functions properly, it responds to bacteria, viruses, and damaged cells by causing inflammation. This inflammation helps rid the body of infection and damaged cells. In autoimmune diseases, however, the immune system mistakenly attacks healthy tissue, which leads to tissue damage and chronic inflammation.

There are more than 100 different autoimmune diseases, including spondylitis, multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, type 1 diabetes, and systemic lupus erythematosus.

Autoimmunity can involve the presence of autoantibodies (antibodies that target normal parts of the body) or other immune dysfunction. Spondylitis is one of several inflammatory diseases that are described as MHC-I-opathies. Major histocompatibility complex class I (MHC-I) is a set of genes that encode certain proteins. These proteins allow the immune system to recognize and target viruses, bacteria, and cancer cells. MHC-I-opathies like spondylitis are autoimmune diseases that are not caused by autoantibodies. Instead, they are caused by abnormal MHC-I proteins that do not function properly. This dysfunction causes an inappropriate immune response.

What Is Spondylitis?

As an autoimmune condition, spondylitis can cause inflammation in the body that leads to back pain (especially in the lower back), joint pain, abnormal new bone growth at joints (ankylosis), and inflammation where ligaments and tendons connect to bone (enthesitis). Spondylitis is also associated with eye inflammation (uveitis), psoriasis, and inflammatory bowel diseases such as Crohn’s disease and ulcerative colitis.

Several types of spondylitis can be classified based on where symptoms occur, severity, cause, and what other related conditions exist. Types of spondylitis include:

  • Ankylosing spondylitis (the most advanced form of spondylitis)
  • Enteropathic arthritis
  • Psoriatic arthritis
  • Reactive arthritis
  • Undifferentiated spondyloarthritis
  • Juvenile spondyloarthritis

Causes of Spondylitis

There is no single cause of spondylitis, but there are specific hereditary and environmental factors that are correlated with spondylitis and autoimmunity. It is believed that both genetic predisposition and environmental exposures account for most cases of spondylitis.

Hereditary Risk Factors and Autoimmune Disease

Proving cause and effect is difficult when it comes to complex disorders like autoimmune disease, but recent research has identified a role for certain proteins in autoimmune disease. People with spondylitis are more likely to have one or more genetic markers (unique forms of genes and proteins).

Human Leukocyte Antigen B27

Human leukocyte antigen B27 (HLA-B27) is an inherited type of HLA protein frequently found in people with spondylitis and related conditions. HLA-B27 is found on the surface of cells and is involved in presenting foreign proteins to white blood cells to initiate an immune response. Many types of spondylitis are correlated with HLA-B27. However, being HLA-B27-positive does not mean you will develop spondylitis. Performing a blood test for HLA-B27 is part of the diagnosis of spondylitis.

ERAP1

ERAP1 is a protein involved in the production of MHC-I proteins (such as HLA-B27). Specific forms of ERAP1 are correlated with spondylitis. It is believed that these forms of ERAP1 can cause spondylitis by producing abnormal HLA-B27 protein, resulting in an immune response against healthy tissue.

Interleukin IL-23 and Interleukin-17

Interleukin-23 and interleukin-17 are proteins. They are used by the immune system to signal white blood cells to initiate an inflammatory response. Specific inherited types of these proteins are associated with spondylitis, especially psoriatic arthritis (or psoriatic spondylitis) and related psoriasis of the skin. Interleukin-17 is known to play a role in inflammatory diseases and is a target for drugs to treat spondylitis.

Environmental Factors and Autoimmune Disease

Environmental risk factors for spondylitis can include certain infections or an imbalance of the normal healthy bacteria in your intestines.

Infection

Reactive arthritis is a type of inflammatory arthritis that falls under the umbrella of spondylitis, although it may not involve the spine. Reactive arthritis occurs after having an infection (usually of the gastrointestinal tract or urinary tract) that results in an autoimmune response. The response causes inflammation in joints throughout the body and can also affect the eyes and urinary tract. People with reactive arthritis are more likely to be HLA-B27-positive, suggesting that an interaction between the genetic predisposition and the infection leads to reactive arthritis.

Intestinal Dysbiosis

Dysbiosis is an imbalance of the good bacteria in the gut. Inflammation caused by dysbiosis plays a role in both reactive arthritis and enteropathic arthritis. It is unclear how dysbiosis can result in spondylitis, but it may involve bacteria entering the bloodstream and causing an immune response that ultimately becomes an autoimmune disorder.

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References
  1. Rheumatologists Make Progress Defining Spectrum of Axial Spondyloarthritis — The Rheumatologist
  2. Overview of Types of Spondylitis — Spondylitis Association of America
  3. Autoimmune Diseases — National Institute of Arthritis and Musculoskeletal and Skin Diseases
  4. Autoimmune Disease List — American Autoimmune Related Diseases Association
  5. ‘MHC-I-opathy’-Unified Concept for Spondyloarthritis and Behçet Disease — Nature Reviews Rheumatology
  6. Major Histocompatibility Complex (MHC) Class I and MHC Class II Proteins: Conformational Plasticity in Antigen Presentation — Frontiers in Immunology
  7. Possible Complications: How Is a Person Affected? — Spondylitis Association of America
  8. HLA-B27 Antigen — Icahn School of Medicine at Mount Sinai
  9. ERAP1 Gene — Medline Plus
  10. The Impact of the ‘Mis-Peptidome’ on HLA Class I-Mediated Diseases: Contribution of ERAP1 and ERAP2 and Effects on the Immune Response — International Journal of Molecular Sciences
  11. ERAP1 Enzyme-Mediated Trimming and Structural Analyses of MHC I-Bound Precursor Peptides Yield Novel Insights Into Antigen Processing and Presentation — Journal of Biological Chemistry
  12. The Role of Polymorphic ERAP1 in Autoinflammatory Disease — Bioscience Reports
  13. IL-23 Drives a Pathogenic T Cell Population That Induces Autoimmune Inflammation — Journal of Experimental Medicine
  14. The Role of IL-17A in Axial Spondyloarthritis and Psoriatic Arthritis: Recent Advances and Controversies — Annals of the Rheumatic Diseases
  15. Anti-IL-17A Treatment Reduces Serum Inflammatory, Angiogenic and Tissue Remodeling Biomarkers Accompanied by Less Synovial High Endothelial Venules in Peripheral Spondyloarthritis — Scientific Reports
  16. Overview of Reactive Arthritis — Spondylitis Association of America
  17. Dysbiosis of the Gut Microbiota in Disease — Microbial Ecology in Health and Disease
  18. Overview of Enteropathic Arthritis/Arthritis Associated With Inflammatory Bowel Disease — Spondylitis Association of America
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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