Connective tissue disease: Addenbrooke’s evaluates new screening test

The clinical immunology department at Addenbrooke’s Hospital, a large teaching hospital in Cambridge, performs around 150,000 autoimmune serology and allergy assays annually, and a similar number of immunochemistry tests including immunoglobulin, protein electrophoresis and complement studies. In addition, the department offers an extensive cellular immunology and immunodeficiency service which performs 90,000 tests annually. Much of the laboratory’s workload comes from the Addenbrooke’s site and from GPs in Cambridgeshire, but the laboratory also carries out a large number of tests for district general hospitals in Suffolk and Norfolk, and the rest of the UK. The hospital boasts one of the few Clinical Pathology Accreditation (CPA)-accredited immunology laboratories, and one of only two consultant clinical immunologists, in the East of England, and so the department fulfils a tertiary testing role on behalf of many smaller hospitals that lack the facilities to perform more specialised follow-up testing.

Connective tissue disease testing
One of the department’s most commonly performed autoimmune serology tests is an antinuclear antibody (ANA) assay for the diagnosis of systemic lupus erythematosus (SLE) and other connective tissue diseases. These systemic autoimmune diseases are characterised by the abnormal structure or function of one or more elements of the connective tissue (eg collagen, elastin or mucopolysaccharides). Connective tissue diseases (CTDs) can be difficult to diagnose because they often begin with generalised non-specific symptoms. Diagnosis is based mainly on clinical findings but is complicated because of the similarity of symptoms. To support diagnosis or exclusion, a number of disease-specific ANAs exist, and screening for these markers can give a strong indication of which CTD is likely to be involved (Table 1).

One of the most commonly employed ANA assays, which has traditionally been perceived as the gold standard, is the HEp-2 indirect immunofluorescence ANA test. This manual assay is non-specific, with four out of five positive results having no clinical relevance, and this is further compounded by the complexity of data interpretation. The test is performed manually, making it laborious and time-consuming, with poor intra- and interlaboratory reproducibility.