Autoimmune disorder

Auto immune disorder

Introduction

The immune system is a collection of special cells and chemicals that fight infection-causing agents such as bacteria and viruses.

An autoimmune disorder occurs when a person's immune system mistakenly attacks their own body tissues.

Autoimmune disorders are broadly grouped into two categories – 'organ-specific' means one organ is affected, while in 'non-organ-specific' disorders, multiple organs or body systems may be affected.

There are around 80 different autoimmune disorders ranging in severity from mild to disabling, depending on which system of the body is under attack and to what degree.

For unknown reasons, women are more susceptible than men, particularly during their childbearing years.

It is thought that sex hormones may be at least partly responsible.

There is generally no cure, but the symptoms of autoimmune disorders can be managed.

Risk factors for autoimmune disorders

The exact causes of autoimmune disorders are not known.

The risk factors seem to include:

Genetics:

A predisposition to autoimmune disorders seems to run in families.

However, family members can be affected by different disorders; for example, one person may have diabetes, while another has rheumatoid arthritis.

It seems that genetic susceptibility alone is not enough to trigger an autoimmune reaction, and other factors must contribute.

Environmental Factors:

A family's susceptibility to autoimmune disorders may be linked to common environmental factors, perhaps working in conjunction with genetic factors.

Gender:

Around three quarters of people with autoimmune disorders are women.

Sex Hormones:

Autoimmune disorders tend to strike during the childbearing years. Some disorders seem to be affected, for better or worse, by major hormonal changes such as pregnancy, childbirth and menopause.

Infection

Some disorders seem to be triggered or worsened by infections.

The National Institute of Environmental Health Sciences (NIEHS) is supporting research to understand how these factors work together to compromise the body’s ability to defend itself and develop into autoimmune diseases.

NIEHS hopes to find clues that will lead to treatments and cures, or ways to prevent the development of these diseases.

NIEHS brought together an interdisciplinary group of experts to evaluate the state of the science regarding the role of the environment and the development of autoimmune diseases.

The findings include:

[1] Exposure to solvents, which are used in thousands of products, including paint thinners, cleaning supplies, and nail polish, contributes to the development of systemic sclerosis.

[2] Smoking contributes to the development of two types of rheumatoid arthritis.

[3] Exposure to fine particles of crystalline silica, a basic component of quartz, granite, and many minerals, contributes to the development of several autoimmune diseases.

[3.1] Workers exposed to these minerals are particularly at risk.

[4] Eating gluten, present in wheat and some other grains, contributes to the development of celiac disease, a disorder that affects the small intestine and commonly causes chronic diarrhea and fatigue.

[5] Taking certain supplements containing L-tryptophan, an essential amino acid used as a dietary supplement, contributes to development of eosinophilia myalgia syndrome, an incurable and sometimes fatal condition involving severe muscle pain.

Pathophysiology

The human immune system typically produces both T cells and B cells that are capable of being reactive with self-antigens, but these self-reactive cells are usually either killed prior to becoming active within the immune system, placed into a state of anergy (silently removed from their role within the immune system due to over-activation), or removed from their role within the immune system by regulatory cells.

When any one of these mechanisms fail, it is possible to have a reservoir of self-reactive cells that become functional within the immune system.

The mechanisms of preventing self-reactive T cells from being created takes place through negative selection process within the thymus as the T cell is developing into a mature immune cell.

Some infections, such as Campylobacter jejuni, have antigens that are similar (but not identical) to our own self-molecules.

In this case, a normal immune response to C. jejuni can result in the production of antibodies that also react to a lesser degree with receptors on skeletal muscle (i.e., myasthenia gravis).

A major understanding of the underlying pathophysiology of autoimmune diseases has been the application of genome wide association scans that have identified a degree of genetic sharing among the autoimmune diseases.

Autoimmunity, on the other hand, is the presence of self-reactive immune response (e.g., auto-antibodies, self-reactive T cells), with or without damage or pathology resulting from it.

This may be restricted to certain organs (e.g. in autoimmune thyroiditis) or involve a tissue in different places (e.g. Goodpasture's disease which may affect the basement membrane in both the lung and the kidney).

There are many theories as to how an autoimmune disease state arises. Some common ones are listed below.

Cryptic determinants/molecular sequestration

Although it is possible for a potential autoantigen to be spatially sequestered in an immune privileged site within the body (e.g. the eye), mechanisms exist to express even these antigens in a tolerogenic fashion to the immune system.

However, it is impossible to induce tolerance (immune unresponsiveness) to all aspects of an autoantigen.

This is because under normal physiologic conditions some regions of a self-antigen are not expressed at a sufficient level to induce tolerance.

These poorly displayed areas of an antigen are called "cryptic determinants."

The immune system maintains a high-affinity repertoire to the cryptic self because the presentation of these determinants was insufficient to induce strong tolerance.

Molecular Mimicry

The concept of molecular mimicry describes a situation in which a foreign antigen can initiate an immune response in which a T or B cell component cross-recognizes self.

The cross reactive immune response is responsible for the autoimmune disease state. Cross-reactive immune responses to self were first described for antibodies.

Altered Glycan Theory

According to this theory the effector function of the immune response is mediated by the glycans (polysaccharides) displayed by the cells and humoral components of the immune system.

Individuals with autoimmunity have alterations in their glycosylation profile such that a proinflammatory immune response is favored.

It is further hypothesized that individual autoimmune diseases will have unique glycan signatures.

Hygiene hypothesis

According to the hygiene hypothesis, high levels of cleanliness expose children to fewer antigens than in the past, causing their immune systems to become overactive and more likely to misidentify own tissues as foreign, resulting in autoimmune conditions such as asthma.

Clinical manifestation / Presentation

Autoimmune disorders fall into two general types: those that damage many organs (systemic autoimmune diseases) and those where only a single organ or tissue is directly damaged by the autoimmune process (localized).

However, the distinctions become blurred as the effect of localized autoimmune disorders frequently extends beyond the targeted tissues, indirectly affecting other body organs and systems.

In some cases, the antibodies may not be directed at a specific tissue or organ.

For example, antiphospholipid antibodies can react with substances (phospholipids) that are the normal constituents of platelets and the outermost layer of cells (cell membranes).

This reaction can lead to the inappropriate formation of blood clots within blood vessels (thrombosis).

Autoimmune disorders can be difficult to recognize and diagnose.

Autoimmune disorders affecting multiple organs can lead to highly variable signs and symptoms that can change in severity over time.

Vague and slow to develop signs and symptoms may be present and can be misleading during diagnosis.

Some of the more common symptoms of autoimmune disorders include fatigue, general feeling of being unwell (malaise), dizziness, joint pain, rash, and low grade fever.

Laboratory tests performed to diagnose autoimmune disorders depend on the particular disorder the health practitioner suspects a person has but usually include blood tests for one or more autoantibodies as well as tests for inflammation such as CRP and ESR.