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X Chromosome and Autoimmunity

Published: 15th Feb, 2024

Context

A groundbreaking study has illuminated the intricate relationship between the X chromosome and autoimmunity.

What are autoimmune Diseases?

  • Autoimmune diseases are conditions in which your immune system mistakenly damages healthy cells in your body. Instead of protecting you from diseases and infections, your immune system mistakenly targets and attacks parts of your own body as if they were foreign invaders. This abnormal response leads to inflammation and damage to various organs and tissues.
  • Common Autoimmune Diseases:
    • Type 1 diabetes: Damages the pancreas.
    • Rheumatoid arthritis (RA): Attacks the joints.
    • Systemic lupus erythematosus (lupus): Can affect multiple body systems.
    • Crohn’s disease, psoriasis, and multiple sclerosis

Xist RNP Complex and Autoimmunity:

  • Xist, a long non-coding RNA (lncRNA) associated with the X chromosome, plays a pivotal role.
  • Its associated ribonucleoprotein (RNP) complexes participate in the formation of immune complexes recognized by the immune system.
  • Intriguingly, male mice producing Xist were more susceptible to severe autoimmune disease.
  • Autoantibodies targeting Xist and related proteins were also found in people with autoimmune diseases, hinting at a potential trigger for autoimmunity.

X Chromosome and Autoimmune Risk:

  • The presence of a second X chromosome has been linked to an increased risk of autoimmune diseases in both sexes.
  • Specific genes on the X chromosome, which escape the usual inactivation process, contribute to this heightened risk.
  • Experimental studies reveal that inducing the formation of these immune complexes in male mice increases disease severity and alters immune cell profiles.
  • Thus, the X chromosome plays a crucial role in driving autoimmune risk, particularly among women.

Transforming Detection and Monitoring:

  • Identifying autoantibodies targeting Xist-associated proteins could revolutionize autoimmune disease detection and monitoring.
  • These findings offer new therapeutic targets and hold promise for developing more sensitive testing and preventive approaches.

Implications for Autoimmunity:

  • Exploring X chromosome-related mechanisms opens new avenues for comprehending and combating these complex conditions.
  • Ongoing research investigates spontaneous germinal center formation in mice and the role of nerve growth factor receptors in autoimmunity.

Chromosomes

Chromosomes are thread-like structures found inside the nucleus of animal and plant cells. Each chromosome consists of protein and a single molecule of deoxyribonucleic acid (DNA). These remarkable entities carry the genomic information from cell to cell, serving as the blueprints for life itself .

Composition:

  • Chromosomes are composed of DNA and histone proteins.
  • The long, thin DNA fibers are coated with nucleosomes, which are formed by these packaging proteins, especially histones.

Hereditary Traits:

  • Chromosomes play a crucial role in heredity.
  • They contain the specific instructions that make each type of living creature unique.
  • These instructions are passed from parents to offspring.

Cell Division:

  • During cell division, chromosomes ensure that DNA is divided equally between the daughter cells.
  • Any irregularities in this process can lead to various diseases and deformities.

Health Implications:

  • Chromosomal aberrations, such as changes in structure or number, can cause genetic disorders like Down’s syndrome and Turner’s syndrome.
  • Defective chromosomes may even contribute to certain types of leukemia in humans.
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