Impact of Autoimmune Disease Diagnosis on Clinical Laboratory

The interplay of various genes determines an individual's susceptibility to an antigen and, by extension, the type of autoimmune disease the patient may suffer.

Dr Vijay Kumar

Autoimmune diseases number more than 80 chronic disabling disorders and affect almost every system in the body. The sites that may be targeted by autoimmunity include nerve, gastrointestinal, endocrine, skin, skeletal and vascular tissues. These diseases may be characterised by the immune system's production of autoantibodies against endogenous antigens with consequent injury to the host tissues and organs. In many diseases, the presence of autoantibodies antedates the disease itself.

It is believed that autoimmune disorders affect five-seven per cent of the population with prevalence as high as 20 per cent in the US population.

Autoimmunity is the underlying cause of diseases afflicting 50 million Americans. This estimate may be conservative. Current research worldwide continues to reveal the role of autoimmunity in other diseases.

Experience with these disorders has shown that early diagnosis is of significant aid to the physician in proper management of the patient. A sound understanding of diagnostic methods for the diagnosis of autoimmune diseases on the part of the laboratory professional in conjunction with knowledge of appropriate tests available for diagnosis is essential to yield positive patient outcomes. This will be even more significant in the future as vaccines become available to treat or ameliorate autoimmune disorders.

Causes of Autoimmunity

The origin and mechanism of autoimmune diseases is still largely a mystery. Autoimmunity seems to result from the interplay of various influences, including environmental and genetic factors. While certain potential environmental links have been identified, the theoretical framework and experimental studies to fully support the environmental hypothesis have not yet been completed. Similarly, genetic studies show genes to be only partly responsible for autoimmune diseases. Studies of identical twins have consistently found there to be a 20-30 per cent chance that a genetically identical sibling will have the same autoimmune disease suffered by a twin. This rate is significantly elevated as compared with a three-five per cent risk for non-identical twins.

The interplay of various genes determines an individual's susceptibility to an antigen and, by extension, the type of autoimmune disease the patient may have. As described by Marrack et al (Nat Med. 2001;7:899-905), the genes of an individual affect susceptibility to autoimmunity at three levels:

1) Genes influence overall reactivity of the immune system and may predispose an individual to autoimmunity.

2) Stimulated immune reactivity may be directed against a particular antigen or tissue by other genes.

3) Other genes may affect the ability of the target tissue to resist or modify immune attack.

As previously noted, environment may also influence the development of autoimmunity at the various levels, affecting the overall reactivity of the immune system or the antigen specific immune response. This may explain the differences in the incidence of various autoimmune disorders in monozygotic twins. For example, the concordance in monozygotic twins for Type 1 diabetes is higher than for systemic lupus erythematosus, Graves's disease and several other autoimmune disorders. This could be due to a combination of the effect of the greater role of the genetic susceptibility in early onset autoimmune disorders as compared to late onset and the relatively greater shared environmental exposures in children as compared with adults. Professor Noel Rose of John Hopkins University in Baltimore, suggests that one half the risk of developing an autoimmune disorder is inherited and the other half derives from the environment.

Classification of Autoimmune Disorders

Autoimmune diseases can be classified as 'organ specific' (e.g. Type 1 diabetes) or 'non-organ specific' (e.g. systemic lupus erythematosus), also known as systemic diseases (Table 1). In organ-specific diseases, lesions are restricted to an organ as an antigen present in the organ is the trigger of autoimmunity. In systemic autoimmunity, there is no single antigen involved and the antigen(s) are ubiquitous. Systemic autoimmune disorders result from immune complexes formed and deposited systemically.

Impact on Clinical Laboratory

Both antibodies and cellular T effector cells may cause tissue damage. If the purpose of the laboratory is to aid the clinician in patient management, then it is very essential that the methods of detecting autoantibodies are specific, sensitive, reliable and reproducible. In addition, laboratories must identify markers which can help to identify disease activity, remission and impending relapse. By making analytic methods available that can satisfy these criteria, the laboratory assumes an essential role in the proper management of the patient.

E-mail: vijaykumar@immco.com
IMMCO Diagnostics, Inc. Buffalo NYUniversity at Buffalo, SUNY Buffalo, NY