Role of autoantibodies in development of novel diagnostics and evidence based therapuetics
In therapeutics, the main task of clinicians is making timely appropriate decisions about the patient's care despite of incomplete clinical information and uncertainty about clinical outcomes. While data being primarily elicited from the history and physical examination for making the diagnosis or for guiding therapeutics, more accountability on outcome of treatment has made physicians look out for precise diagnostic aids leading to evidence-based therapeutics. More information is required not only to document but also to gather adequate evidence, which forms the basis of the diseases.
In a nation like ours, where adequate professionally guided diagnosis is grossly lacking in most of the clinical situations, physicians are hard pressed to rely on conventional skills of physical examinations and patient history, although the conventional skills are purely personal and empirical and subject to wide variations of diagnosis and treatment. In many cases these conventional skills may be misleading and a reason for occurrence of preventable casuality.
In many emergencies, empirical treatment may appear more practical than evidence-based treatment. The review of enhanced morbidity and mortality burden would definitely favour evidence-based treatment, wherever it is possible.
The problems with present-day diagnostics are difficult procedure, expensive and poor accessibility. Magnetic resonance imaging, Computer tomography need huge investments, trained skilled technician-support and is expensive. The advent of enzyme-linked immunosorbent assays and radioimmuno assays have revolutionized the diagnosis of most of the infectious diseases including AIDS. However a large number of important diseases like diabetes mellitus, rheumatoid arthritis and cancer have remained out of the gambit of these inexpensive tools. It is highly desirable to have inexpensive diagnostic tools for these diseases looking at their future epidemic trends with huge economic and social burden. It also helps as prognostics, which indicates early confirmation of future morbidity and mortality of individuals. This may help one to take prophylactic measures that may help to slow down and delay the onset of disease.
It has been observed that in many diseases of autoimmune origin, the antigens of the disease can be detected 3 to 6 years earlier to the full development of the disease and are in fact early warning signals of the future disease. It has been established that autoimmune disorders are the result of loss of tolerance to self-proteins. The autoimmune disorders are still a challenge to scientific community as there is no definite knowledge about cause and treatment is available as on today. The disease of autoimmune disease can be classified as systemic and organ specific for example rheumatoid arthritis and diabetes mellitus respectively. The classification of some important autoimmune diseases is given in Table 1 and Table 2.They can be further classified based on the manifestation of pathogenesis mediated by cellular or antibody.
It is generally observed, in spite of diversifying mechanisms of disease, in all autoimmune diseases the circulating autoantibodies are capable of attacking various useful proteins like receptors and ion channels in an antigen antibody fashion and rendering these dysfunctional.
It is also interesting to note that in most of these autoimmune disorders, the circulating autoantibodies can be precisely detectable in serum many years before the onset of visible symptoms of the disease it self. The circulating autoantibodies are a characteristic feature, which can be useful predictors of future diseases. Autoantibodies may not be directly responsible for many of the manifestations of the disease, but they are early markers of future disease, which is present in healthy individuals. Looking at this, an opportunity emerges which can screen large populations regarding the future burden of the disease.
In the era of human genomics, genetherapy and molecular medicine, it would not be difficult to develop a cost effective diagnostics/ prognostics, for diseases like diabetes mellitus, rheumatoid arthritis, cancer etc which are posing as major epidemics of the future with a huge social and economic burden.
The early detection of the autoantibodies can be a good prognostic that can be done by screening the serum. Such identification might allow for immunological treatment where the prognosis may be slowed down or prevented which is highly desirable. Even though with the present day technology, it may be unable to achieve such a goal, the early diagnosis would be of great help in avoidance of life threatening emergencies like thyroid storm and Addison's crisis. The advents of supporting technologies like high throughput protein array has raised the hopes of possibilities of simultaneous analysis of hundreds of autoantibodies in one run. This technology would allow prospective study of large populations like communities with a sample of drop of blood. Many studies have assessed GAD, anti-insulin, anti-islet-cell and /or anti IA-2A in non-diabetic offsprings of parents with autoimmune diabetes. Similar studies on diseases like rheumatoid arthritis, in which Anti - CCP was detected in one third of the population scanned.
-- The author is with Pharmacy Group, Birla Institute of Technology and Science, Pilani