Autoimmunity Disease

Autoimmunity is the failure of an organism to recognise its own constituent parts (down to the sub-molecular levels) as "Self", as a result of which it attempts to mount an immune response against its own cells and tissues. Any disease that results from such an aberrant immune response is termed an autoimmune disease, the prominent examples being Systemic Lupus Erythematosus (SLE), Sjögren's syndrome and Rheumatoid Arthritis (RA).

The illusory misconception that an individual's immune system is totally incapable of recognising "self" antigens is not new. Ehrlich, at the beginning of the twentieth century, proposed the concept of horror autotoxicus, wherein a 'normal' body does not mount an immune response against its own tissues. Any autoimmune response thus was perceived to be abnormal and postulated to be connected with human disease. Now, it is accepted that autoimmune responses are vital to the development and functioning of vertebrate immune system, and central to the development of immunological tolerance to self-antigens. The latter concept has been somewhat prematurely termed natural autoimmunity. Autoimmunity should not be confused with alloimmunity.

Genetic Factors

It is now well established that certain individuals are genetically susceptible to the development of autoimmune diseases. However, this susceptibility is not inherited in a simple Mendelian segregation, but usually tends to be polygenic. That even individuals with genetic predisposition always do not develop autoimmune diseases could only mean that the pathogenesis of such disorders must also be multifactorial.

The main genetic loci involved in the body's immune system include the genes for immunoglobulins and T-cell receptors, both of which are involved in the recognition of antigens, and the major histocompatibility complex (MHC) antigen system. Of these, the first two are inherently variable and susceptible to recombination, and sporadic variations may give rise to lymphoid cells which are capable of self-reaction.

However, certain MHC class II genotypes are strongly correlated with specific autoimmune diseases:

• HLA DR2 is strongly correlated with SLE, Multiple Sclerosis, and negatively correlated with insulin-dependent diabetes mellitus (IDDM).
• HLA DR3 is correlated strongly with Sjögren's, Myasthenia gravis, SLE and IDDM.
• HLA DR4 is correlated with the genesis of RA, IDDM and Pemphigus vulgaris.

Fewer correlations exist with MHC class I molecules, the most notable and consistent being the association between HLA B27 and ankylosing spondylitis.

Sex

Sex also seems to have a major role in the development of autoimmunity; most of the known autoimmune diseases tend to show a female preponderance, the most important exception being ankylosing spondylitis which has a male preponderance. The reasons for this are unclear. Apart from inherent genetic susceptibility, several animal models suggest a role for sex steroids.

Diagnosis

Diagnosis of autoimmune disorders largely rests on accurate history and physical examination of the patient, and high index of suspicion against a backdrop of certain abnormalities in routine laboratory tests (example, elevated C-reactive proteins). In several systemic disorders, serological assays which can detect specific autoantibodies can be employed. Localised disorders are best diagnosed by immunofluorescence of biopsy specimens.