Saavedra, Mónica Susana 1; Filgueira, Elsa Elena 2; Pessacq, María Teresa 3; Schweizer, J.R.4; Calcagno, María de Luján 5; Fenili, Cecilia Andrea 6.
La hCG, por ser sintetizada por el trofoblasto placentario, desde su descubrimiento ha sido considerada «la hormona del embarazo». Pero, además, es producida por la hipófisis en hombres y mujeres sanos, como así también por tumores de origen no trofoblástico. En fluidos biológicos circula una gran variedad de moléculas relacionadas a la hCG, producto de su síntesis y metabolización. El dosaje de algunas de las formas moleculares tiene potencial valor diagnóstico en diferentes patologías. Describimos la producción de hCG en diferentes situaciones clínicas, su heterogeneidad y microheterogeneidad molecular y su implicancia en la medición de la hormona por diferentes inmunoensayos (IEs). Medimos hCG en muestras de suero correspondientes al primer trimestre de embarazo normal, con 7 IEs que emplean diferentes juegos de anticuerpos en su diseño y tienen diferente especificidad para reconocer las formas moleculares de la hormona. El análisis de concordancia de resultados de cada uno de los métodos re s p e c t o del IQMA (DPC IMMULITE hCG), nos indicó que no todos son intercambiables. Esto sería atribuible a la heterogeneidad molecular de la hormona, a la diferente especificidad de los Acs. monoclonales utilizados para el diseño de cada IE y/o a la estandarización de éstos. Es imprescindible entonces, caracterizar cada IE, examinando su capacidad para detectar las diferentes formas moleculares de la hCG que puedan tener implicancia clínica
The human chorionic gonadotrophyn (hCG), because of being synthesized by placentary trophoblast, has been considered the pregnancy hormone. But it is also produced by hypophisis in healthy men and women, as in nontrophoblastic tumors. A wide variety of hCG related molecules circulate in biological fluids; they are the product of its synthesis and metabolization: the intact, nicked and clivated molecule, the intact and modified free subunities, besides the degradation products (molecular heterogeneity). There are also variants with different carbohydrate composition (molecular microheterogeneity). We can find then, a wide variety of circulating fragments with molecular weight (MW) from 9.5 kD, like beta core, to 40 kD, the MW of the predominant form in the early weeks of pregnancy, that is the hyperglicosilated hCG. The proportion of the different molecular forms of hCG vary in sera samples of patients in different clinical situations: normal and Ectopic or extrauterine pregnancy, Early pregnancy loss (EPL) or biochemical pregnancy, Gestational Trophoblastic Disease, Down Syndrome screening, Quiescent Trophoblastic Disease (QTD), Unexplained Elevated hCG (UE). These two last pathologies are characterized by persistently low levels of hCG (below 50 mIU/ml), production of hCG with a low grade of glycosilation that is characteristic in the second and third trimesters of pregnancy. Despite being widely used the methods of measuring of hCG in different clinical situations, we must take into account that the dosage of free beta subunit in serum and/or the beta core fragment in urine are more sensible markers in some types of nontrophoblastic cancers, germinal cells tumors, bladder and ovary cancer, etc. Furthermore, recent development of a test for hyperglicosilated hCG would raise the predictive value of this marker in Down Syndrome screening in second trimester. The immunoassays (IAs) commonly used in the laboratory measuring the hCG have diff e rent abilities to re c o g n i z e all molecular forms. We have compared the results of hCG dosed in sera samples corresponding to patients in the first trimester of pregnancy, obtained with seven different IAs: hCG MAIAclone (IRMA/MAIA, Biodata Diagnostic), hCG Total (ICMA, Chiron Diagnostic), Total Beta (MEIA, Abbott), Nea Tact (IRMA, DSL), HCG Immulite (ICMA, DPC), HCG STAT and HCG+b (ECLIA, Roche Diagnostic). These methods, as they use in its design different sets of antibodies, present different specificity. In normal pregnancy, the intact hCG is the predominant molecular form, but it is possible to detect all the related forms of hCG in smaller proportions. We compared values obtained with each IA with the DPC Immulite method, which would recognize all the molecular forms of hCG of clinical interest. We found significative differences between the different methods, that could be attributed to the molecular heterogeneity and micro h e t e rogeneity of hCG, the diff e rent specificity of antibodies used in each IA, the recognition in a nonequimolecular way of the different molecular forms and the problems in standardization. In short, to some causes inherent to the hormone and the specificity of the IA evaluated, and others inherent to measuring by IA, like its standardization. The characteristics of the intern a t i o n a l p reparations used as re f e rence and of the partially purified calibrators (containing diff e rent proportions of intact, clivated, or free subunities of hCG) used by the IA manufacturers, make the hCG standardization difficult. From the point of view of diagnosis and follow up of clinical situations where the dosage of hCG is employed, all of the IAs studied are adequate for pregnancy diagnosis because a good correlation is observed among results, but the absence of agreement observed between some of them would indicate that they are not interc h a n g e a b l e ; t h e re f o re, the monitoring of patients must be made with the same method. It is necessary, because of their d i fferent specificities, to characterize each IA, examining its ability to detect the different molecular forms of hCG that may have clinical implications.