AN IMMUNOLOGICALLY ANOMALOUS LUTEINIZING-HORMONE VARIANT IN A HEALTHY WOMAN

An investigation was undertaken to characterize an immunological LH variant in a 31-yr-old healthy woman whose serum LH was either poorly or not at all recognized by two monoclonal antibodies. The two antibodies recognize epitopes present on the intact LH dimer, but not on the free subunits. It was found that the immunologically aberrant LH of the subject was bioactive, as evidenced by an in vitro bioassay for LH. Nothing in the personal history of the subject or in the results from a number of hormone analyses revealed any endocrine abnormalities. In a GnRH stimulation test, the increase in immunoreactive LH using two reference immunometric assays for LH was less than 10% of the mean response of five control subjects. In relative terms, the maximal increase in LH in the subject was only 60-100%, in contrast to 340-560% for the control subjects. The bio/immuno ratio of the LH in the subject was high and was further increased in the GnRH stimulation test. A low proportion of acid LH isoforms in basal and stimulated samples from the subject was in agreement with the high bio/immuno ratio. Gel filtration studies showed the presence of molecular species of apparently lower molecular size than the intact LH, but different from the free beta-subunit. The results suggest the presence of fragments of the alpha-beta-dimer where at least part of the beta-subunit has been lost. A pedigree analysis involving the parents, siblings, and children of the subject strongly suggests a genetic origin of the LH variant described with an autosomal mode of inheritance. This report on an immunological variant of LH illustrates the potential dangers of using monoclonal based immunoassays where a protein hormone with fully maintained biopotency may be partially or totally missed due to the monospecificity of the immunoreagent. This possibility should be kept in mind when inappropriately low levels of gonadotropins are detected in diagnostic routine.