Autoimmune disease is a pathological condition which is caused by an adaptive autoimmune response directed against an antigen within the body of the host. In other words, the body mistakenly attacks its own cells. The disease can affect every part of the human body. It may be systemic, affect single organs or organ systems or attacking several organ systems simultaneously. Thus, the symptoms are vary correspondingly depend on which parts of the body are attacked by the immune system and on the development of the disease. However, these definitions can be unclear since it is often difficult to differentiate the causality when dealing with a human disease. It is very beneficial to consider the evidence of an autoimmune etiology of a human disease with three degrees of stringency.
AUTOIMMUNE DISEASE – CRITERIA
How to determine if autoimmunity is the cause of the disease rather than an accompanying feature or an outcome? The demonstration of auto-antibodies is the first step in the diagnosis of these diseases, however the antibodies might not be the actual pathogens of the disease. Autoantibodies can occur naturally and are common in all immunologically competent person and might even increase nonspecifically while in the course of disease or injury. Hence, the miniscule presence of autoantibodies does not automatically determine a cause-and-effect relationship, because the autoantibodies might be the result, not the cause, of the disease process. However it is important to emphasize, that the presence of autoantibody responses has great value in diagnosing and prognosing numerous human diseases.
Autoantibodies may be present many years before the diagnosis of diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Type 1 diabetes mellitus (DM) and antiphospholipid syndrome. Combined with genetic information or family history, the presence of autoantibodies may be highly predictive of the later onset of an autoimmune disorder.
Direct evidence – The disease can be produced by showing autoimmune response. Direct evidence usually involves transfer of autoantibody from a patient to a healthy recipient, either an animal or a human. A few instances of such transfers have been successfully performed.
Reproduction of pemphigus by injection of patient serum into a neonatal mouse.
Maternal-fetal transmission (transplacental transmission) of myastenia gravis, Graves’ disease, and the complete heart block associated with lupus and Sjögren’s disease. The clinical manifestations in the offspring are temporary, because the autoantibody in these cases is provided through passive transfer of serum from the mother.
Indirect evidence – The second level of proof of causality is indirect evidence which requires the availability of an appropriate animal model where the necessary transfer studies can be carried out. Different animal models are implemented :
Reproduction of disease in animals via immunization with the appropriate antigen.
Autoimmune thyroiditis in the mouse after immunization with thyroglobulin – Hashimoto’s thyroiditis (chronic autoimmune thyroiditis).
Myocarditis after immunization of susceptible mice with murine myosin.
Naturally occurring disease in animals that resembles its human counterpart.
Many aspects that resemble human SLE (Systemic Lupus Erythematosus) have been found in particular genetic strains of mice.
A disease closely resembling Type 1 (autoimmune) diabetes.
Disease resulting from manipulation of the immune system.
Models of inflammatory bowel disease have been described in animals in which particular cytokines such as interleukin (IL)-2 and IL-10 have been eliminated.
Autoimmune dilated cardiomyopathy develop in mice which are deficient in programmed cell death-1 (PD-) immuno-inhibitory coreceptor.
Circumstantial evidence – This is the lowest level of proof, which is the one most commonly available to connect a mysterious human disease to autoimmunity.
The hazards of using this kind of evidence as the basis for concluding that a disease is caused by autoimmunity have been previously described. Natural autoantibodies are common and might rise nonspecifically in the course of a disease process.
Autoimmune diseases tend to cluster, maybe simply because they share a number of genetic susceptibility traits. For examples, a single person will have more than one autoimmune disease, and family members share the very same or even other autoimmune diseases.
A particular bias to certain HLA haplotypes is shown by most of the autoimmune diseases, usually the Class II category. Because genes that are important in regulating the immune response are encoded by the Class II Major Histocompability Complex (MHC), some rational association may exist between the genetic constitution and susceptibility to a specific autoimmune disease.
Most, but not all, autoimmune diseases are more common in women than men. Therefore, a sex bias provides increased circumstantial evidence of an autoimmune etiology. In addition, new information on the differing pathogenic mechanisms involved in men and women has been provided by comparing of the sex-based differences in autoimmune diseases.
A disease’s response to immunosuppressive therapy is usually an important clinical indicator of autoimmune etiology. If effective symptomatic therapy can be obtained by immunosuppression, therefore, demonstrating the etiologic agent of the disease may seem less essential.