Systemic autoimmune diseases - Discover Biotech

In this article, I describe types of systemic autoimmune diseases and their symptoms.

Table of Contents

What are autoimmune diseases?

Autoimmune diseases happen when a person’s immune system attacks its healthy cells. Immune-stimulatory lymphocytes or antibodies recognize self-components causing cell lysis, which results in an inflammatory response in the affected organ.

Autoimmune diseases may be systemic or organ-specific. In an organ-specific autoimmune disease, the antigen unique to a single organ or gland is targeted. In systemic autoimmune diseases the antigens found in multiple tissues or organs are targeted, leading to inflammation and physiologic damage at multiple places in the body.

Some of the known systemic autoimmune diseases are discussed below.

Various systemic autoimmune diseases

1. Lupus (Systemic Lupus Erythematosus)

Lupus is a systemic autoimmune disease, which is more common in women than men. The symptoms of this disease start to appear at the age of 20-40. African American and Hispanic women suffer the most than others. The reason for the development of this disease is still unknown. It is a disease having a genetic aspect, as in identical twins, the suffering of one of them may result in the development of the disease in another one. If a person in a family is suffering from lupus, then there is a chance of contracting the disease by close relatives of that person.

Symptoms

The individuals affected with lupus produce autoantibodies to a wide array of cells or common cellular components. The butterfly rash across the nose and cheeks is a marked symptom of this disease. The other symptoms include fever, weakness, arthritis, kidney dysfunction, and frequent skin rashes. Autoantibodies are secreted specifically for RBCs. The platelets can cause complement-mediated lysis, which ultimately results in hemolytic anemia and thrombocytopenia respectively.

Activation of the complement system

Auto-antibodies make immune complexes with different nuclear antigens and get them stored along the walls of small blood vessels. This results in the development of a type III hypersensitivity reaction. The complement system gets activated by the complexes of auto-antibodies and antigens and generates membrane attack complexes and complement fragments. The walls of the blood vessels are damaged by the membrane attack complexes and complement fragments. This leads to cause diseases like vasculitis and glomerulonephritis.

When there is excessive complement activation, it results in the production of certain elevated complement fragments in serum, resulting in the accumulation of neutrophils and attachment with the vascular endothelium. With the progress of time the number of circulating neutrophils declined, resulting in the obstruction of many small blood vessels. This ultimately causes extensive tissue damage.

The diagnostic test for Lupus

The diagnostic test for SLE (Systemic Lupus Erythematosus) involves the extraction of serum dilutions from patients and getting it mixed with cells (nucleoprotein, histones, DNA, or nucleolar RNA) attached to a glass slide.

The application of indirect immunofluorescence staining involves the addition of fluorescently labeled secondary antibodies against human antibodies. The result shows a characteristic staining pattern of the nucleus, thus confirming the presence of anti-nuclear antibodies and a speculative positive diagnosis.

The thorough study of animal models of lupus has helped to get much information about the disease. The research has shown that certain specific genes put a balance between regulatory and effector lymphocytes.

The most old and renowned model among many models is the New Zealand mouse, where F₁ hybrids of New Zealand Black and New Zealand white mice often get affected with a severe autoimmune syndrome closely resembling human SLE. However, mild symptoms are shown by each of the parent strains.

2. Rheumatoid arthritis

Rheumatoid arthritis is a common autoimmune disorder affecting more women than men. People between the age group 40-60 and mainly women get affected by the disease. As in the disease lupus, rheumatoid arthritis possesses a firm genetic susceptibility factor.

The major symptoms of the disease appear in the form of chronic inflammation of the joints. Apart from inflammation of joints, people may also affect their hematologic, cardiovascular, and respiratory systems.

The rheumatoid factors

Persons affected with rheumatoid arthritis produce antibodies that react with citrullinated protein antigens (CPAs) and a group of auto-antibodies known as rheumatoid factors. A CPA is produced when an arginine residue gets converted into the nonstandard amino acid citruline.

The rheumatoid factor is the Fc region of the antibody IgG, and thus, antibody is produced against antibodies. When rheumatoid factors bind to normal circulating antibodies, the formation of immune complexes takes place and is deposited in joints. Deposition of immune complexes in joints causes the activation of the complement cascade. This ultimately leads to type III hypersensitivity reaction and chronic joint inflammation.

Rheumatoid arthritis is associated with gum disease and smoking, and the association may activate and influence the level of citrullination of proteins in the mucosa, thus triggering the generation of anti-self antibodies in individuals susceptible to rheumatoid arthritis.

3. Multiple sclerosis

Multiple sclerosis is a chronic autoimmune disorder affecting the central nervous system. People are getting affected by this disease differently. Multiple sclerosis has similarities with lupus and rheumatoid arthritis, as more women than men are affected by it. The affected people start to show symptoms between the ages of 20 to 40, though younger women are more affected.

Persons affected with multiple sclerosis produce autoreactive CD4⁺ T cells and T_H17 cells secreting IL-17 cytokines. These T cells recruit other cells to the site and enhance the inflammation along the myelin sheath of nerve fibers in the brain and spinal cord.

Neurologic dysfunction and appearance of symptoms

The nerve fibers are surrounded and protected by the myelin sheath. Any inflammation in it leads to its breakdown, ultimately resulting in neurologic dysfunction. Neurologic dysfunction breaks the communication between the brain and the rest of the body. Thus, the symptoms vary from numbness in the limbs to paralysis or loss of vision.

The signs and symptoms of the disease vary from person to person, depending upon the location and the severity of damage to the nerve fiber. Both genetic and environmental factors are associated with the disease. Along with the alleles at the DRB1 locus of MHC class II, many other potential loci are also connected with this disease.

Factors causing multiple sclerosis

According to epidemiological studies, multiple sclerosis is more common in the Northern Hemisphere than in the Southern Hemisphere. In the United States, the disease is widespread in comparison to other countries. The occurrence of the disease is at high risk when relocation from low to high-incidence regions during the early years takes place.

So, in addition to genetic factors, environmental components early in life have a remarkable effect on the risk of contracting the disease. The environmental factors include diet, smoking, obesity, and exposure to sunlight, which increase the susceptibility to the disease. Exposure to sunlight is associated with vitamin D levels, which is an immune modulator and can promote anti-inflammatory responses.

Immunity to the disease

Multiple sclerosis is arbitrated solely by the T cells of our immune system. The two components of the myelin sheath (surrounding neurons in the central nervous system) are myelin basic protein and proteolipid protein (any one protein). Any one of the two can be used for immunization in several species for inducing the disease.

The experimental animals show demyelination and paralysis by developing cellular infiltration of the central nervous system. Most of the animals succumb to the disease, whereas some have milder symptoms and possess a chronic form of the disease.

Conclusion

When comparing different types of systemic autoimmune diseases, it shows that in all three diseases, more women are affected than their male counterparts. The different diseases differ in their symptoms, and numerous factors are responsible for their onset.

Lupus is a disease having a genetic aspect. In identical twins, the suffering of one of them may result in the development of the disease in another. If a person in a family is suffering from lupus, then there is a chance of contracting the disease by close relatives of that person. People suffering from lupus have a characteristic butterfly rash across their nose and cheeks.

The major symptoms of rheumatoid arthritis appear in the form of chronic inflammation of the joints. Other than joint inflammation, people may also affect their hematologic, cardiovascular, and respiratory systems.

Multiple sclerosis is a chronic autoimmune disorder affecting the central nervous system. The signs and symptoms of the disease vary in individuals, depending upon the location and the severity of nerve fiber damage. Both genetic and environmental factors are associated with multiple sclerosis.