Immunology through the ages

Hilda Crockett, of Siemens Medical Solutions Diagnostics, takes us from the birth of immunology as a science to the present day

WHEN the concept of immunity first became apparent to human observers in ancient times, no-one could possibly have imagined that that it would one day underpin a key area of diagnostic science. When plague struck the city of Athens in 430 BC, Thucydides recorded his observation that people who had recovered from a previous bout of the disease could then go on to nurse the sick without contracting the illness for a second time themselves. Subsequent references to this phenomenon have also been found in writings left by other ancient societies, but it was not until the 19th and 20th centuries that the specific interactions of antibodies and antigens became known to modern science.

The introduction of antigens such as viruses, bacteria, bacterial toxins and other foreign substances to the body is now known to trigger the production of antibodies by the immune system in animals and humans - unless, of course, the process is disabled in some way. Immunodeficiency of this kind is produced by conditions such as chronic granulomatous disease and AIDS in which parts of the immune system fail to provide an adequate response to the invasion of pathogens. Malfunctions of the immune system also include conditions such as rheumatoid arthritis, systemic lupus erythematosus, Hashimoto’s disease and myasthenia gravis which are characterised by autoimmunity whereby the immune system attacks the body of its own host. Allergies and asthma are also classified as immunological disorders in terms of hypersensitivities in which the immune system responds inappropriately to contact with harmless compounds. Hypersensitivity may also be manifested as a grossly exaggerated immunological response.

Generally speaking, however, the immunological bonds that exist between antibodies and antigens are efficient and highly specific. This fact has allowed them to be used as tools for the diagnosis of disease and assessment of immunological responses in a variety of ways, including techniques such as immunohistochemical staining, immunoblotting and enzyme-linked immunosorbent assay (ELISA) tests. The accuracy of such tests, combined with their relative speed and simplicity, has secured their place in the development of many of the so-called ‘rapid’ methods that are used in laboratories today.

While the evolution of analytical instrumentation for clinical laboratories initially focused on the automation of routine clinical chemistry tests in the 1970s, it was not long before automated immunodiagnostics analysers started making an appearance. Today, automated platforms for immunoassays are regarded as integral to the range of services provided by modern blood science departments. Capability in the area of testing for infectious diseases such as Cytomegalovirus, Epstein Barr Virus (EBV), Hepatitis A, B and C, Herpes, HIV, Rubella, Syphilis and Toxoplasmosis also ensure a place for such analysers in centres which undertake high workload microbiology diagnostics.

The range of tests that can be performed on such analysers is extensive, encompassing many different key areas of clinical diagnostics. Of these, perhaps the most frequently used on a routine basis fall under the categories of thyroid functions and reproductive endocrinology, but automated immunoassays also have an important role to play in therapeutic drug monitoring and haematinics (anaemia testing) too. Many clinical laboratories are finding that allergy screening panels and testing for reactions to specific allergens form a growing part of their immunoassay workload, while tests of relevance to diabetic patients (urinary albumin, insulin and C-peptide) are also always in demand.

The range of immunoassay-based tumour markers is constantly being extended, with well-established markers such as CEA, CA 15-3, CA 125 and CA 19-9 being complemented by innovative new additions to the assay menu such as HER-2/neu (relevant to breast cancer) and complexed prostate specific antigen (PSA). A similar situation pertains in the area of cardiovascular markers, where the traditional range of tests encompassing myoglobin, CK-MB and troponin I (TnI) is being supplemented by newly-developed diagnostic markers such as B-type natriuretic peptide (BNP) and TnI-Ultra.

The list goes on. Automated immunoassays are also now commercially available for measuring growth hormones, markers of autoimmunity, inflammation and bone metabolism and specific metabolic markers such as adrenocorticotropic hormone (ACTH), cortisol and homocysteine.

Use of these automated platforms enables laboratories to automate a high proportion of their routine and esoteric immunoassay workloads - and there are plenty more important new assays in the development pipeline. In the menu category of autoimmune marker assays, for example, an antinuclear antibody (ANA) screening test is currently under development, along with a dsDNA antibody assay. A panel of celiac disease markers is also in the pipeline, encompassing anti-gliandin IgA and anti-gliandin IgG to complement the anti-tTG IgA assay which is already available for Immulite analysers.

As the barriers between the traditional laboratory disciplines of clinical chemistry and immunodiagnostics break down in the move towards formation of core blood science laboratories, it should come as no surprise that some diagnostic assays targeted at immunological diseases are now appearing on the menus of chemistry instruments. For example, the specific protein assay panels on the ADVIA Centaur and Immulite instrument families in Siemens Medical Solutions Diagnostics’ range now include automated methods for both rheumatoid factor (RF) and C-reactive protein (CRP). These analytes, which are both associated with autoimmune related inflammation, are quite likely to be requested for individual samples at the same time as various immunoassays, creating the logistical problem of moving those samples efficiently between the two types of analytical platform involved. Traditionally, the fulfilment of such requests has required laboratory staff to spend a considerable amount of time keeping track of samples and manually transferring them from one type of instrument to another - until, that is, the benefits of laboratory automation come into play.

More and more laboratories are now discovering how much easier the management of such samples becomes following the installation of an automated track system. Where once samples were constantly being moved manually by staff backwards and forwards between specimen reception, the main analytical area and the laboratory’s refrigerators, implementation of a track system takes care of all the routing between instruments automatically. In many hospital laboratories, this has allowed staff to experience the logistical and efficiency benefits of ‘true’ random access analysis for the very first time.

In the Blood Sciences Department at North Hampshire Hospitals NHS Trust in Basingstoke, for example, an ADVIA WorkCell track is now being used to connect the laboratory’s four automated chemistry and immunoassay instruments (two ADVIA 1650 Chemistry Systems and two ADVIA Centuar Immunoassay Systems) and began making a significant impact on the efficiency of laboratory workflow within a month of installation.

An ADIVA WorkCell track can be used to connect automated chemistry and immunoassay instruments

In particular, use of the track has made a positive impact upon the way in which staff utilise their time in the laboratory. While a small team of people is involved in the initial setting up of the track for operation each morning, just a single person is then needed to run the two ADVIA 1650s and another to run the two ADVIA Centaur systems. A senior member of staff has been appointed to fulfil the role of track master. This arrangement has had the effect of freeing up other staff members to concentrate on manual testing areas and an increased point of care repertoire. Best of all, highly qualified staff no longer find themselves running around chasing after samples for multi-discipline analysis and manually moving them around.

It is a similar story at Barnsley Hospital NHS Trust, where a total of six automated analysers - not only clinical chemistry and immunoassay, but haematology as well - have recently been connected to an automated ADVIA LabCell track. Here, the system also encompasses the pre-analytical stages of sample handling in terms of automated tube de-capping and centrifugation. Use of the automated track system has addressed the recognised problem of staff having to spend too much time on activities which were perceived as not adding value to the laboratory testing service, such as moving specimens between the various analysers. In fact, prior to its installation, one of the biomedical scientists in the laboratory had filmed a time-lapse video comprising a series of still photographs taken of staff at 30 second intervals as they moved around the department. When his colleagues watched the video, they were all surprised by the extent to which people appeared to be constantly in motion, moving specimens from the reception area, on and off the different analysers and then into storage and out again. The track has subsequently minimised the incidence of these “non value added” steps, allowing trained staff to concentrate on the skilled core jobs that they were employed to do.

These same sentiments have been echoed at Bradford Royal Infirmary, where the ADVIA WorkCell track system now provides an automated sample transport link between the laboratory’s two ADVIA 1650 and ADVIA 2400 Chemistry analysers and two ADVIA Centaur Immunoassay Systems, once again making a significant difference to the efficiency of the department. Instead of struggling to prioritise samples and keep pace with a workload exceeding 1,000 blood tubes a day, the processing of test requests - especially those involving both chemistry and immunoassay analysers - is now considered to be much easier than ever before.

All these examples illustrate how automated Immunodiagnostics has now taken its rightful place alongside clinical chemistry and haematology in modern blood science laboratories as a key analytical discipline. Just as the bonds which are formed between specific antigens and antibodies underpin the all-important science of Immunology, so the efficient processing of high volume immunoassay and clinical chemistry tests can now go hand in hand.

Hilda Crockett
Hilda is Market Development Manager at Siemens Medical Solutions Diagnostics.