RESUMO
Participants of the Second International Workshop (WS) on human chorionic gonadotropin (hCG) of the International Society of Oncology and Biomarkers Tissue Differentiation 7 (ISOBM TD-7) have characterized in detail a panel of 69 antibodies (Abs) directed against hCG and hCG-related variants that were submitted by eight companies and research groups. Specificities of the Abs were determined using the First WHO International Reference Reagents for six hCG variants, i.e., hCG, hCGn, hCGß, hCGßn, hCGßcf, and hCGα, which are calibrated in SI units, and hLH. Molecular epitope localizations were assigned to the ISOBM-mAbs by comparing ISOBM-Ab specificity, sandwich compatibility, and mutual inhibition profiles, to those of 17 reference monoclonal (m)Abs of known molecular epitope specificities. It appeared that 48 Abs recognized hCGß-, 8 hCGα-, and 13 αß-heterodimer-specific epitopes. Twenty-seven mAbs were of pan hCG specificity, two thereof with no (<0.1%; epitope ß1), 12 with low (<1.0%; epitopes ß2/4), and 13 with high (>>1%; epitopes ß3/5) hLH cross-reactivity. The majority of hCGß epitopes recognized were located in two major antigenic domains, one on the peptide chain of the tips of ß-sheet loops 1 and 3 (epitopes ß2-6; 27 mAbs) and the second around the cystine knot (e.g., epitopes ß1, ß7, and ß10; 9 mAbs). Four mAbs recognized epitopes on hCGßcf-only (e.g., epitopes ß11 and ß13) and six mAbs epitopes on the remote hCGß-carboxyl-terminal peptide (epitopes ß8 and ß9 corresponding to amino acids 135-144 and 111-116, respectively). For routine diagnostic measurements, methods are used that either detect hCG-only, hCGß-only, or hCG together with hCGß or hCG together with hCGß and hCGßcf. Sandwich assays that measure hCG plus hCGß and eventually hCGßcf should recognize the protein backbone of the analytes preferably on an equimolar basis, should not cross-react with hLH and not be susceptible to blunting of signal by nonmeasured variants like hCGßcf. Such assays can be constructed using pairs of mAbs directed against the cystine knot-associated epitope ß1 (Asp10, Asp60, and Gln89) in combination with epitopes ß2 or ß4 located at the top of ß-sheet loops 1 + 3 of hCGß involving aa hCGß20-25 + 68-77. In summary, the results of the First and Second ISOBM TD-7 WSs on hCG provide the basis for harmonization of specificities and epitopes of mAbs to be used in multifunctional and selective diagnostic hCG methods for different clinical purposes.
Assuntos
Anticorpos Monoclonais/imunologia , Gonadotropina Coriônica/imunologia , Epitopos/imunologia , Sequência de Aminoácidos , Afinidade de Anticorpos/imunologia , Especificidade de Anticorpos/imunologia , Antígenos/imunologia , Gonadotropina Coriônica/química , Gonadotropina Coriônica/genética , Ensaio de Imunoadsorção Enzimática , Mapeamento de Epitopos/métodos , Humanos , Espectrometria de Massas , Modelos Moleculares , Dados de Sequência Molecular , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Isoformas de Proteínas/imunologia , Estrutura Secundária de Proteína , Estrutura Terciária de ProteínaRESUMO
INTRODUCTION: For many women, and particularly rural women, birthing locally and within their own community is important for personal, social and/or cultural reasons. If concerns about the woman or her baby mean transfer to a secondary or tertiary facility is necessary, this can be disruptive and stressful, especially if road transfer is complicated by terrain, weather or distance, as is often the case in rural New Zealand. The objective of this study was to explore the number of and reason for transfers during labour and birth for well women, close to full term, from primary rural maternity facilities to specialist care in rural New Zealand. METHODS: This retrospective survey of 45 rural maternity units in the North and South Islands of New Zealand was conducted over a 2 year period ending on 30 June 2006. The participants were the 4678 women who began labour in a rural facility during this time period. RESULTS: The survey response rate was 66.6%. The data revealed that 16.6% of women who commenced labour in a rural unit were transferred in labour or within 6 hours of birth; 3% of babies born in rural units were transferred after birth and up to 7 days post-birth. The primary reason for maternal transfer was slow progress in labour (49.67%). Of the 123 babies transferred, this was most often due to respiratory problems (43%). Key features of the rural context (times and distances to be travelled, geological and climatic characteristics, types of transport systems and availability of local assistance) influenced the timeliness of the decision to transfer. CONCLUSIONS: Within New Zealand's regionalised perinatal system, midwives make cautious decisions about transfer, taking into account the local rural local circumstances, and also the topography as it impacts on transport.