title: Circulating antibodies to monoclonal immunoglobulins used in a follitropin assay may cause incorrect fertility diagnosis.
abstract: We report grossly overestimated serum immunoreactive follitropin concentrations in an infertile man with normal spermatogenesis using a solid phase fluoroimmunoassay. The assay employs two monoclonal antibodies directed against two separate antigenic sites on the human follitropin molecule (DelFIA, Pharmacia). Determination of serum immunoreactive follitropin with a RIA based on polyclonal antiserum (WHO reagents), and of bioactive follitropin with the Sertoli-cell bioassay, revealed normal serum follitropin concentrations. Preincubation of the patient's sample with normal mouse serum or addition of normal mouse serum to the assay buffer neutralized the effect of the interfering substance in the DelFIA follitropin assay. Gel chromatography showed the interfering substance to have a relative molecular mass greater than 200,000. The substance is probably an antibody against mouse immunoglobulins, which cross-links the monoclonal mouse antibodies used in the DelFIA. The unknown incidence of heterophilic antibodies in human serum and the lack of preventive steps in some commercially available kits may lead, as in this case, to misdiagnosis in some patients.
authors.affiliation: Institut für Reproduktionsmedizin, Universität Münster.
authors.forename: F
authors.initials: F
authors.lastname: Jockenhövel
authors.forename: S A
authors.initials: SA
authors.lastname: Khan
authors.forename: E
authors.initials: E
authors.lastname: Nieschlag
mesh_terms: D000328:Adult; D000906:Antibodies / Q000276:immunology; D000911:Antibodies, Monoclonal; D003937:Diagnosis, Differential; D003951:Diagnostic Errors; D015200:Fluoroimmunoassay; D005640:Follicle Stimulating Hormone / Q000032:analysis* / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology; D007248:Infertility, Male / Q000175:diagnosis*; D008297:Male
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D007136:Immunoglobulins; D005640:Follicle Stimulating Hormone