Search

Systemic vasculitis, although rare, is often diagnosed late and long after the onset of symptoms. The small vessel vasculitides are recognized clinically by their multisystem presentation, markers of inflammation and evidence for an acute glomerulonephritis (GN), with the most apparent organ involved directing referral to secondary care. Routine laboratory tests are usually non-specific in systemic vasculitis but the use of anti-neutrophil cytoplasmic antibodies (ANCAs) and glomerular basement membrane (GBM) antibodies can aid diagnosis, treatment and monitoring decisions. These antibodies are detected and quantified by indirect immunofluorescence (IIF) and antigen-specific enzyme-linked immunosorbent assay (ELISA), usually in combination for ANCA, and ELISA systems (or direct IIF on kidney biopsy) for GBM antibodies. The presence or absence of ANCA does not confirm or exclude the diagnosis of systemic vasculitis but negative and positive predictive values will be strongly influenced by clinical presentation. Various large studies have been unable to conclude that following serial ANCA titres has great clinical utility in each case but each patient must be considered on its own merits; for example the reappearance of ANCA in a patient who was rendered ANCA negative following treatment is more likely to indicate relapse. The adoption of consensus guidelines that direct testing towards patients with rapidly progressive GN, pulmonary haemorrhage, persistent and destructive ear, nose and upper airways problems, such as subglottic tracheal stenosis, a retro-orbital mass and cutaneous vasculitis with systemic features or peripheral neuropathy, will greatly increase the clinical utility and positive predictive value of these tests. [ABSTRACT FROM AUTHOR]

This review describes the aetiology of the major thyroid antigens. Iodination of thyroglobulin produces multiple antigen configurations which are functionally active but immunologically distinct. The thyroid stimulating hormone (TSH) receptor is a two-subunit glycoprotein; the extracellular A subunit is recognized by thyroid stimulating antibodies, while those antibodies recognizing the B subunit, located much nearer the cell surface, appear to function as blocking antibodies. Thyroid peroxidase (TPO), originally described as thyroid microsomal antigen, is present on the apical surface of thyroid follicular cells and is the antigen involved in cell-mediated cytotoxicity. Multiple B-cell-reactive epitopes exist, each giving rise to different antibodies. The aetiology and mechanics of the autoimmune cellular and antibody responses involves a combination of human leucocyte antigen (HLA) linkage, genetics and environmental factors to determine the initial and subsequent stages of the development of autoimmune thyroid disease. Depending on the antibody, a combination of enzyme-linked immunosorbent assay for TPO and thyroglobulin and bioassays and/or radioimmunoassay for TSH receptor antibodies are used to estimate their concentrations. The other conditions with which autoimmune thyroid diseases are associated include, for example, pernicious anaemia, connective tissue disorders, diabetes, coeliac disease, mood disorders like depression and fertility-related problems such as miscarriage, infertility, in vitro fertilization failure, pre-term delivery and postpartum thyroiditis. Often, there is no cause-and-effect relationship between them and it is debatable in some cases whether it is worthwhile monitoring patients with autoimmune thyroid disease for other conditions or vice versa. The review also itemizes the circumstances in which it might be useful to measure each antibody (i.e. the use of TPO antibodies in investigation of goitre, diagnosis of Graves' and Hashimoto's disease and the prediction of risk of developing hypothyroidism during subclinical thyroid disease; TSH receptor antibodies in maternal and neonatal hyperthyroidism and thyroglobulin antibodies in the monitoring and treatment of thyroid carcinoma). Finally, taking the current literature into account, an algorithm is recommended for the most effective use of these antibodies in the investigation of autoimmune thyroid disease. [ABSTRACT FROM AUTHOR]

Background: There are reports in the literature describing artefactually raised phosphate concentrations in serum samples of patients with myeloma. However, IgA paraproteins have been reported only rarely as a potential cause. Methods: Following the detection of a grossly elevated phosphate concentration in a patient with an IgA paraprotein and another with an IgG paraprotein, we estimated phosphate concentrations in a further 73 patients with paraproteins using the Bayer ADVIA 1650 and Ortho Vitros 950 analysers. The latter method has been reported to be unaffected by pseudohyperphosphataemia. Results: Deproteinization of the serum samples containing the IgA and IgG paraproteins showed that they were responsible for the interference. No significant difference in serum phosphate concentrations measured by the two analysers was noted for the larger study of serum IgG or IgM paraproteins. However, a statistically significant but clinically trivial difference in phosphate concentration was noted for serum IgA paraproteins, with the Ortho Vitros 950 giving slightly higher phosphate concentrations. Deproteinization of these samples yielded similar phosphate concentrations. Phosphate estimation in serum samples without paraproteins using both analysers yielded results that were not statistically different. Conclusion: On occasion, serum samples containing IgA paraproteins may give rise to erroneous phosphate concentrations when the Bayer ADVIA is used [ABSTRACT FROM AUTHOR]

Background: The demand for screening for coeliac disease has grown rapidly over the last few years. Laboratories depending on immunofluorescence assays are faced with an increasing workload using a labour-intensive test, and an alternative to this test has been sought. This study compares tissue transglutaminase (TTG) and endomysium antibodies (EMA) in a routine clinical laboratory situation. Methods: An immunofluorescence IgA EMA test was compared with a guinea pig TTG antibody ELISA for 816 unselected requests for gut antibody screening. Discrepant results were investigated more fully using a variety of human source TTG antigen kits. Results: Guinea pig TTG ELISA and EMA assays showed agreement for 93·6% of samples. Four samples were misclassified and 48 samples gave false positive TTG results. Study of 46 EMA samples (this group included 39 of the 'discrepant' negative EMA/positive guinea pig TTG group) using three different human purified and/or recombinant TTG sources showed that 42 patients had no TTG antibodies using human sources, three were misclassified and one patient had negative EMA and positive TTG results that could not be readily explained. Further study of 32 EMA positive samples showed almost complete agreement between the human source TTG kits. Conclusions: We can recommend the replacement of EMA with ELISA for TTG antibodies for the routine screening for coeliac disease, but all positive TTG antibodies should still be followed up with IgA EMA and samples should be screened for IgA deficiency. [ABSTRACT FROM AUTHOR]

Background: To investigate the reasons why general practitioners (GPs) request rheumatoid factor (RF) assays, we studied 200 consecutive requests for RF from general practice in 1995. Method: By means of an audit questionnaire, we studied 100 negative, 50 positive and 50 borderline RF results and compared these with the presenting symptoms that prompted the request, the GPs' understanding of the significance of the result, the referral intention and behaviour of the GP, and finally, the patient outcome after 5 years. Results: There was an 80% response rate. The presenting symptoms closely matched the American Rheumatism Association revised criteria for the classification of rheumatoid arthritis, indicating that the requests were made on valid clinical grounds, with polyarthralgia, morning stiffness and joint pain being the most common. Most GPs considered a negative or positive result to be meaningful, in that a positive RF meant that a referral was more likely than with a negative or borderline result, even in the presence of appropriate symptoms in all three groups. Seventeen to thirty per cent felt that the test excluded or confirmed RA. The result appeared to influence this decision to a greater extent than it should. A 5-year follow-up on these patients showed that 26/40 patients with positive RF were referred, and that 25 of them developed a rheumatic disease of some kind, with 17 patients eventually being diagnosed with RA. Only 17/80 patients with negative RF were referred, the remainder having no autoimmune problem evident after 5 years, 11 of them developing a rheumatic disease, and only three being diagnosed with RA. Conclusions: Although this is a locally based study, we believe the conclusions would be applicable to all laboratories and GPs undertaking these tests. RF requests are made on valid clinical grounds by GPs, but there may be an over-reliance on the results as regards referral behaviour. If patients were referred on clinical grounds, this would significantly lengthen consultants' waiting lists. [ABSTRACT FROM AUTHOR]

This report describes a case of IgD lambda myeloma which was discovered only following investigation of a suspicious *low gamma region". If anti-IgD mvestigations had not been carried out, it may have been misinterpreted as Bence Jones myeloma. The case illustrates that evaluation of serum and urine in cases of suspected myeloma is mandatory and that the possibility of IgD myeloma in cases that appear to be 'free light chain" paraproteins only should be investigated. [ABSTRACT FROM AUTHOR]