The appropriate use of antineutrophil cytoplasmic antibody (ANCA) testing in rheumatic diseases.

The antineutrophil cytoplasmic antibody (ANCA) test is now available in most routine diagnostic immunology laboratories. Improvement, simplification and standardisation of the testing methodology have enabled it to become more reliable and accessible to clinicians. ANCA has strong association with and is most useful in the diagnosis and management of the ANCA-associated vasculitides which include Wegener's granulomatosis, microscopic polyarteritis, Churg-Strauss syndrome and primary pauci-immune necrotising and crescentic glomerulonephritis. It is found in lower frequency in the other vasculitides and collagen vascular diseases, in chronic inflammatory bowel disease and autoimmune liver disease, and in miscellaneous infective and neoplastic disorders. While the gold standard for ANCA testing remains the indirect immunofluorescence (IIF) assay, identification of ANCA-specific antigens such as proteinase 3 and myeloperoxidase has enabled the development of antigen-specific tests. The antigen-specific solid-phase assays have comparable sensitivity with IIF assays and improved specificity in some instances. However, appropriate use of the ANCA test requires full knowledge of its capabilities and limitations, and the results should always be correlated with clinical data. In particular, it is important to understand that it is not only test sensitivity and specificity, but patient selection that contributes to the positive predictive value and clinical relevance of the test result.

Confirmatory serological testing of blood donors positive on TPHA screening in Singapore.

Seventy-two blood donors who were tested positive by the Singapore Blood Transfusion Service (SBTS) for Treponema pallidum haemagglutination (TPHA) test, were evaluated at the Department of Sexually Transmitted Diseases Clinic (DSC) between November 1994 to December 1996. All underwent syphilis serological testing, including rapid plasma reagin test (RPR), TPHA test and fluorescent treponemal antibody-absorption (FTA-Abs) test. All except one (98.6%) were confirmed TPHA positive by the DSC. Of the 71 TPHA-confirmed-positive donors, 53 (74.6%) were subsequently tested positive for FTA-Abs and 18 (25.4%) were tested negative for FTA-Abs. Twenty-two (31%) of the 71 TPHA-positive blood donors had reactive RPR and 49 (69%) had non-reactive RPR. Of the 22 TPHA-positive donors who had reactive RPR, 19 (86%) had positive FTA-Abs (13 late latent syphilis, 4 serological scar, one late congenital syphilis, one secondary syphilis), and 3 (14%) had negative FTA-Abs (all late latent syphilis). Of the 49 TPHA-positive donors who had non-reactive RPR, 34 (69%) had positive FTA-Abs (24 late latent syphilis, 9 serological scar, one late congenital syphilis) and 15 (31%) had negative FTA-Abs (12 late latent syphilis, 2 serological scar, one false-positive TPHA). Only one TPHA-positive donor referred by the SBTS subsequently turned out to have negative syphilis serology at the DSC. Overall, 68 (95.8%) TPHA-positive donors who had a past history of sexual exposure were managed as treated or untreated syphilis, regardless of their RPR or FTA-Abs results. However, FTA-Abs was found to be useful in the management of 3 (4.2%) TPHA-positive blood donors in the absence of a history of sexual exposures.

A study of treponema pallidum haemagglutination positive blood donors in Singapore.

The Treponema Pallidum Haemagglutination (TPHA) test has been used for screening of syphilis among blood donors in Singapore since September 1992. Among the 79 500 donations that were screened between September 1992 and December 1993, 191 were tested positive (incidence rate of 0.24%). Seventy-two donors (37.7%) were evaluated at the Department of Sexually Transmitted Disease Control clinic. Seventy-nine percent of these donors had high risk sexual exposure and 33.3% had a history of sexually transmitted diseases. Eighty-three percent of the donors were diagnosed to have late latent syphilis, 9.7% were diagnosed to have a serological scar and the remaining had secondary syphilis, early latent syphilis and a false positive reaction. At least 65.3% of these donors would have been missed if the reagin test was used alone as the screening test. Thus, the TPHA test is a good marker for screening those who have high risk sexual behaviour and it is a more sensitive test than the reagin test for screening blood donors.

Genetic polymorphism within HLA-A*02: significant allelic variation revealed in different populations.

HLA-A2 is present at high frequency in most populations, as identified by serological and biochemical means. The value of these methods is limited by their failure to discriminate between the products of the 14 known allelic HLA-A*02 variants. The great majority of genetic polymorphism which defines the allelic variants is found in exons 2 and 3 of the A*02 genes. These exons encode the alpha-1 and alpha-2 domains of the HLA Class I molecules, and variation within the genes may influence the peptide binding specificity of the gene products of each allele. Failure to accurately assign the allelic types has implications in transplantation, in interpretation of cellular assays and in the understanding of HLA disease associations. We have developed a method for determining the 14 known alleles of HLA-A*02 by use of ARMS-PCR to determine the degree of variation of HLA-A*02 alleles in 3 different population groups. Considerable variation was found in the relative frequencies of particular A*02 alleles between Caucasian, oriental and black individuals. Our results indicate the importance of ethnic origin in terms of the expected HLA-A*02 allelic profile, and emphasize the functional significance of allele specific subtyping of HLA-A*02.