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Bertholf, Ph.D. Associate Professor of Pathology University of Florida Health Science Center/JaxjjfHuman anti-animal antibodiesFirst described in 1971 by Ammann and Hong Potential to cause positive or negative interferences Anti-isotype or anti-idiotype Anti-mouse antibodies are most common Incidence is not certainZ>D@ NTwo-site  sandwich enzyme immunoassay 8HAMA  bridging interferenceHAMA blocking interference Competitive immunoassay HAMA blocking interference Case ReportEThe laboratory director was consulted by a gynecologist about discrepant CA-125 results on a patient being monitored for recurrence of a surgically removed ovarian tumor. CA-125 results from a referral laboratory had been consistently high and increasing, while results from the hospital laboratory were within normal limits.FFCA-125FA large glycoprotein expressed by tissues originating from the mllerian ducts Mab OC 125 was isolated by Bast and colleagues in 1981, using cells from a serous papillary cystadenocarcinoma Useful for detecting and monitoring ovarian tumors Also elevated in endometrial, pancreatic, breast, colorectal, lung and GI carcinomas HU@"Ut * <E : Clinical utility of CA-125*Lacks sensitivity and specificity as a screening test for ovarian cancer Normal in 50% of stage I ovarian cancers PV+ 5% Very sensitive indicator of recurrence following surgical resection Failure to return to normal after chemotherapy is indicative of drug-resistant diseasevI2DWI+ DW  )Follow-up studiesHAMA quantitation (IRMA)* Result = 196 ng/mL (0  188) CA-125 with heterophilic blocking reagent* Without blocking reagent: 211.5 U/mL With blocking reagent: 11.0 U/mL *Scantibodies, Inc., Santee, CAZZ+ZGZ Z ) G    4 ' Sources of foreign IgG exposure <Imaging reagents Pharmaceuticals Vaccines Abzymes (proposed)* (Incidence of HAMAClinical trials 0-100% reported Population studies 72 of 10,000 blood donors (1990 abs.) 92 of 1,008 blood donors (1986, indir.) 51 of 67 blood donors (1991) 8 of 10 infants (1991)Ly7+ Conclusions HAMA can cause clinically significant elevations in CA-125 assays Different immunoassays may not respond equally to the presence of HAMA The population frequency of HAMA is not known, but is likely to increase Interference may occur at modest concentrations of HAMA Z *  ` ` ̙33` 333MMM` ff3333f` f` f` 3>?" dd@0|?" dd@   " @ ` n?" dd@   @@``PT $   @ ` ` p>> (    60 "P  T Click to edit Master title style! !$  0 "  RClick to edit Master text styles Second level Third level Fourth level Fifth level!     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