자가면역 Autoimmunity. From Johns Hopkins Medical school

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Definition of Autoimmunity

Autoimmunity is the presence of antibodies (which are made by B lymphocytes) and T lymphocytes directed against normal components of a person (autoantigens). These components are called autoantigens or self-antigens and typically consist of proteins (or proteins complexed to nucleic acids). The antibodies and T lymphocytes that recognize autoantigens are called “autoantibodies” and “autoreactive T cells“.
Positive ANA
Example of a serum containing ANA as it appears under the microscope.

Autoimmunity is very common

If we use autoantibodies as an indicator for autoimmunity, we find there are many, many types of autoantibodies, directed against many different self-antigens. Thus, it is not surprising that if we were to test the serum broadly enough, we would find some autoantibodies in most “healthy” individuals. Similar reasoning applies to autoreactive T cells, although in the clinical laboratory it is much more complicated to test for T cells than for autoantibodies.

An additional proof that autoantibodies and autoreactive T cells can be present in individuals who do not have clinical evidence of autoimmune disease comes from the new types of cancer treatment based on immunotherapy. Cancer patients who are treated with inhibitors of immune checkpoints (such as CTLA-4 and PD-1) develop a broad activation of their effector T cells, which is the basis for eliminating the tumor cells. This broad activation of effector T cells, however, unleashes in a relatively short time a variety of immune-related side effects that resemble the autoimmune diseases occurring in the absence of cancer immunotherapy. The appearance of these autoimmune events secondary to the use of cancer immunotherapy strongly suggests that autoreactive T cells and autoreactive B cells (i.e., autoantibodies) do exist in healthy individuals, but are kept under control by regulatory mechanisms.

ANA graph 2
Prevalence of ANA in the general population by age and gender (Guo YP et al Curr Ther Res, 2014).

Autoantibodies are an excellent biomarker for autoimmunity

Since the beginning of the autoimmunity field, autoantibodies have been the tool used by clinical laboratories to diagnose and monitor autoimmunity. There are literally hundreds of different autoantibody tests a physician can order nowadays. The most common autoantibody test is the so-called ANA (for anti-nuclear antibody), which is performed using a technique called immunofluorescence. In the ANA test, the patient serum is incubated with cells fixed on a glass slide (these cells, called HEp-2, are a human epithelial cell line derived from a patient with laryngeal cancer). If the serum contains autoantibodies specific for antigens located in the nucleus of the HEp-2 cells, the antibodies will bind to these antigens. The binding is then revealed by the addition of a commercially-available antibody that recognizes all human antibodies and has been chemically modified by the coupling with a dye. The antigen-antibody complexes then “light up” when ultraviolet light is shined on the glass slide and observed under a fluorescent microscope.

ANAs are often found in the general population, even in the absence of any autoimmune disease. As the line graph shows, the prevalence of ANAs in the general population increases with age, and it is higher in women than men.

Classification Criteria

Autoimmune diseases can be classified according to several criteria. One of them is the location of the autoimmune attack. Based on this criterion, autoimmune diseases are distinguished into systemic or organ-specific. Although artificial, this classification scheme is useful for orienting patients and primary care physicians to the appropriate specialist.

Systemic: Affects Many Organs

Systemic autoimmune diseases are those where the autoantigens are found in almost any type of cell in the body, for example the DNA – protein complexes. Consequently, the pathological damage involves many different organs and tissues. Typical systemic autoimmune diseases are rheumatoid arthritis, systemic lupus erythematosus, scleroderma, and dermatomyositis. These diseases are managed by rheumatologists, and in fact the terms “systemic autoimmune disease” and “rheumatic autoimmune diseases” are often used interchangeably.

Organ-specific: Affects One Main Organ

Organ-specific autoimmune diseases are those where a particular organ or tissue is preferentially targeted by the patient’s immune system. For example, the thyroid gland in patients with Graves disease, the beta cells of the endocrine pancreas in patients with type 1 diabetes, or the skin in patients with vitiligo.

How many autoimmune diseases are there?

Many—more than 100. It is difficult, however, to provide an exact number because autoimmune diseases:

  • can challenging to define. Scholars may disagree on the criteria that need to be fulfilled to consider a disease “autoimmune” (i.e, caused by autoimmune mechanisms).
  • are clinically heterogenous, with numerous subtypes and variants. For example, in multiple sclerosis one could distinguish the primary progressive from the relapsing-remitting forms. In thyroiditis one could distinguish the juvenile, the classic, and the form occurring in older persons (known as idiopathic mixedema). Should the different subtypes considered different diseases or should they combined under a single name? As always, definition is critical. Changing how a disease is defined can drastically influence its prevalence.
  • require a vast breadth of knowledge. In order to make a comprehensive list of autoimmune diseases, there has to be somebody who is familiar with all of them and their numerous clinical variances. Quite a difficult task.

With that said, a list of autoimmune diseases of autoimmune diseases has been assembled by the American Autoimmune Related Disease Association. By examining this list you can see that autoimmune diseases can affect pretty much any organ or tissue in the body, so they cast a very broad spectrum of clinical manifestations and patient phenotypes.

From Johns Hopkins Medical school