heterophile antibodies


Summary: Antibodies elicited in a different species from which the antigen originated. These antibodies are directed against a wide variety of interspecies-specific antigens, the best known of which are Forssman, Hanganutziu-Deicher (H-D), and Paul-Bunnell (P-B). Incidence of antibodies to these antigens--i.e., the phenomenon of heterophile antibody response--is useful in the serodiagnosis, pathogenesis, and prognosis of infection and latent infectious states as well as in cancer classification.

Top Publications

  1. Verburg F, Wäschle K, Reiners C, Giovanella L, Lentjes E. Heterophile antibodies rarely influence the measurement of thyroglobulin and thyroglobulin antibodies in differentiated thyroid cancer patients. Horm Metab Res. 2010;42:736-9 pubmed publisher
    The aim of the study was to determine the impact of heterophile antibodies on the measurement of serum thyroglobulin (Tg), thyroglobulin recovery, and thyroglobulin antibody levels in differentiated thyroid carcinoma patients...
  2. Jennemann R, Sandhoff R, Grone H, Wiegandt H. Human heterophile antibodies recognizing distinct carbohydrate epitopes on basidiolipids from different mushrooms. Immunol Invest. 2001;30:115-29 pubmed
    ..higher mushrooms, it was detected that sera of normal adult human subjects contained IgG2 and IgM heterophile antibodies (hetAbs) that immunoreacted with these lipids...
  3. Nozawa S, Xing P, Wu G, Gochi E, Kearns Jonker M, Swensson J, et al. Characteristics of immunoglobulin gene usage of the xenoantibody binding to gal-alpha(1,3)gal target antigens in the gal knockout mouse. Transplantation. 2001;72:147-55 pubmed
    ..Gal o/o mouse can serve as a useful model for examining the genetic control of antibody/antigen interactions associated with the humoral response to pig xenografts in humans. ..
  4. Lindeborg E, Kumagai Braesch M, Tibell A, Moller E. Continued production of xenoimmune antibodies 6-8 years after clinical transplantation of fetal pig islet-like cell-clusters. Xenotransplantation. 2001;8:273-83 pubmed
    ..Some patients also produce xenoreactive IgG1 antibodies directed against non-Gal alpha 1,3Gal epitopes. ..
  5. Wu G, Gochi E, Jin Y, Swensson J, Starnes V, Cramer D. Maturation of xenoantibody gene expression during the humoral immune response of rats to hamster xenografts. Xenotransplantation. 2001;8:291-302 pubmed
  6. Teranishi K, Alwayn I, Buhler L, Gollackner B, Knosalla C, Huck J, et al. Depletion of anti-Gal antibodies by the intravenous infusion of Gal type 2 and 6 glycoconjugates in baboons. Xenotransplantation. 2003;10:357-67 pubmed
    ..iii) The addition of PLL-Gal to the immunosuppressive regimen was associated with a high incidence of morbidity and mortality without a clear histopathologic entity underlying the cause of death. ..
  7. Zahorsky Reeves J, Gregory C, Cramer D, Patanwala I, Kyles A, Borie D, et al. Similarities in the immunoglobulin response and VH gene usage in rhesus monkeys and humans exposed to porcine hepatocytes. BMC Immunol. 2006;7:3 pubmed
    ..Rhesus monkeys are an appropriate preclinical model for testing novel reagents such as those developed using structure-based drug design to target and deplete antibodies to porcine xenografts. ..
  8. Dehoux J, de la Parra B, Latinne D, BAZIN H, Gianello P. Characterization of baboon anti-porcine IgG antibodies during acute vascular rejection of porcine kidney xenograft. Xenotransplantation. 2002;9:338-49 pubmed
    ..The deleterious effects of both IgM and IgG antibodies observed during AVR showed the crucial need for treatment controlling the cells producing anti-porcine antibodies. ..
  9. Zhu A, Hurst R. Anti-N-glycolylneuraminic acid antibodies identified in healthy human serum. Xenotransplantation. 2002;9:376-81 pubmed
    ..Furthermore, this anti-NeuGc activity is detectable in 85% of healthy humans, implicating the involvement of NeuGc in hyperacute rejection and the importance of developing strategies for removing NeuGc for clinical xenotransplantation. ..

More Information


  1. Ferro P, Swaggerty C, Kaiser P, Pevzner I, Kogut M. Heterophils isolated from chickens resistant to extra-intestinal Salmonella enteritidis infection express higher levels of pro-inflammatory cytokine mRNA following infection than heterophils from susceptible chickens. Epidemiol Infect. 2004;132:1029-37 pubmed
    ..These data show a relationship between in vitro heterophil function, increased pro-inflammatory cytokine mRNA expression, and increased resistance to SE in 1-day-old chicks. ..
  2. Dufour J, Hamilton M, Rajotte R, Korbutt G. Neonatal porcine Sertoli cells inhibit human natural antibody-mediated lysis. Biol Reprod. 2005;72:1224-31 pubmed
    ..This suggests that NPSCs may be able to survive humoral-mediated rejection in a clinical situation. ..
  3. Kleihauer A, Gregory C, Borie D, Kyles A, Shulkin I, Patanwala I, et al. Identification of the V genes encoding xenoantibodies in non-immunosuppressed rhesus monkeys. Immunology. 2005;116:89-102 pubmed
    ..These animals represent a clinically relevant model to identify the immunological basis of pig-to-human xenograft rejection. ..
  4. Bolland M, Chiu W, Davidson J, Croxson M. Heterophile antibodies may cause falsely lowered serum cortisol values. J Endocrinol Invest. 2005;28:643-5 pubmed
    We describe a case where interference by heterophile antibodies in a cortisol immunoassay led to a falsely lowered serum cortisol level. As part of a diagnostic workup for fatigue, a 42-yr-old woman was found to have a low 9...
  5. Rood P, Hara H, Ezzelarab M, Busch J, Zhu X, Ibrahim Z, et al. Preformed antibodies to alpha1,3-galactosyltransferase gene-knockout (GT-KO) pig cells in humans, baboons, and monkeys: implications for xenotransplantation. Transplant Proc. 2005;37:3514-5 pubmed
    ..However, our results suggest that, compared to the cynomolgus monkey, the baboon may be a more suitable model to study antibody-mediated rejection of GT-KO pig grafts. ..
  6. Tseng Y, Moran K, Dor F, Sanderson T, Li W, Lancos C, et al. Elicited antibodies in baboons exposed to tissues from alpha1,3-galactosyltransferase gene-knockout pigs. Transplantation. 2006;81:1058-62 pubmed
    ..It remains unclear whether these antibodies are directed towards shared SLA determinants or other pig antigens, and whether antibodies with specificity for allelic SLA determinants are also present, but at lower titer. ..
  7. Zahorsky Reeves J, Kearns Jonker M, Lam T, Jackson J, Morris R, Starnes V, et al. The xenoantibody response and immunoglobulin gene expression profile of cynomolgus monkeys transplanted with hDAF-transgenic porcine hearts. Xenotransplantation. 2007;14:135-44 pubmed
    ..This antibody binds to the Gal carbohydrate but does not induce the rapid rejection of the xenograft when expressed at high levels as early as day 8 post-transplantation. ..
  8. Giovanella L, Keller F, Ceriani L, Tozzoli R. Heterophile antibodies may falsely increase or decrease thyroglobulin measurement in patients with differentiated thyroid carcinoma. Clin Chem Lab Med. 2009;47:952-4 pubmed publisher
    To examine the prevalence of significant interference from heterophile antibodies (HAb) in the measurement of serum thyroglobulin (Tg), we evaluated a large cohort of samples from patients with differentiated thyroid carcinoma (DTC)...
  9. Katopodis A, Warner R, Duthaler R, Streiff M, Bruelisauer A, Kretz O, et al. Removal of anti-Galalpha1,3Gal xenoantibodies with an injectable polymer. J Clin Invest. 2002;110:1869-77 pubmed
    ..Furthermore there was no apparent acute or chronic toxicity associated with GAS914 treatment in primates. We conclude that GAS914 may be used therapeutically for the specific removal of alphaGal Ab's. ..
  10. Hedlund M, Padler Karavani V, Varki N, Varki A. Evidence for a human-specific mechanism for diet and antibody-mediated inflammation in carcinoma progression. Proc Natl Acad Sci U S A. 2008;105:18936-41 pubmed publisher
    Patients with cancer have circulating heterophile antibodies that agglutinate animal red cells via recognition of the mammalian cell surface sialic acid N-glycolylneuraminic acid (Neu5Gc), which was long considered an oncofetal antigen in ..
  11. Aly T, Devendra D, Barker J, Liu E, Yu L, Eisenbarth G. Heterophile antibodies masquerade as interferon-alpha in subjects with new-onset type 1 diabetes. Diabetes Care. 2004;27:1205-6 pubmed
  12. Ryan C, Dutta C, Simo R. Role of screening for infectious mononucleosis in patients admitted with isolated, unilateral peritonsillar abscess. J Laryngol Otol. 2004;118:362-5 pubmed
  13. Milgrom F, Czechowski D. A normal organ antigen and its corresponding antibodies in pathological human sera. Int Arch Allergy Immunol. 2004;135:243-6 pubmed
    ..Furthermore, an identical antigen was demonstrated in 5 of 58 pathological sera. The antigen under study did not belong to any group of known heterophile antigens and it was devoid of organ and tissue specificity. ..
  14. Gruber A, Hanson S. Factor XI-dependence of surface- and tissue factor-initiated thrombus propagation in primates. Blood. 2003;102:953-5 pubmed
    ..aFXI also prolonged the APTT, but the PT and BT were unaffected. Thus, antithrombotic targeting of FXI might inhibit thrombosis with relatively modest hemostatic impairment versus strategies targeting other coagulation factors. ..
  15. Tsutsui Y, Ikeda M, Takeda M, Matsumoto S. Excitability of small-diameter trigeminal ganglion neurons by 5-HT is mediated by enhancement of the tetrodotoxin-resistant sodium current due to the activation of 5-HT(4) receptors and/or by the inhibition of the transient potassium current. Neuroscience. 2008;157:683-96 pubmed publisher
  16. Irgang M, Sauer I, Karlas A, Zeilinger K, Gerlach J, Kurth R, et al. Porcine endogenous retroviruses: no infection in patients treated with a bioreactor based on porcine liver cells. J Clin Virol. 2003;28:141-54 pubmed
    ..The assays used are specific and sensitive, and correlated in their diagnostic value. The data indicate that no PERV infection had occurred in none of the patients treated with the CellModule bioreactor containing porcine cells. ..
  17. Platt J. Immunobiology of xenotransplantation. Transpl Int. 2000;13 Suppl 1:S7-10 pubmed
    ..Research during the past decade has shed light on the elements of the immune system responsible for the rejection of xenografts and has provided novel and incisive therapies which might be applied to these problems. ..
  18. Wang B, Tu C, Hsieh L, Tai H, Chiu Y, Lee J, et al. Rapid detection of human HLA transgenes in pigs by fluorescence in situ hybridization (FISH) for adjuvant study of human xenotransplantation. Xenotransplantation. 2004;11:471-5 pubmed
    ..We conclude that FISH is both sensitive and labor-efficient in confirming and differentiating transgenic pigs for multiple rejection-regulatory genes by visualizing individual integration sites in chromosomes or interphase nuclei. ..
  19. Di Serio F, Caputo M, Zaninotto M, Ottomano C, Plebani M. Evaluation of analytical performance of the Pathfast cardiac troponin I. Clin Chem Lab Med. 2009;47:829-33 pubmed publisher
    ..The 99th percentile limit of the cTnI distribution in the reference population was 0.013 microg/L. The data indicate that the cTnI Pathfast method may be suitable for helping clinicians in the management of patients with ACS. ..
  20. Ghebremariam Y, Smith S, Anderson J, Kahn D, Kotwal G. Intervention strategies and agents mediating the prevention of xenorejection. Ann N Y Acad Sci. 2005;1056:123-43 pubmed
    ..Here the different modulatory approaches and agents mediating interventions in xenorejection are discussed. ..
  21. Bell A, Fortune B, Sheeler R. Clinical inquiries. What test is the best for diagnosing infectious mononucleosis?. J Fam Pract. 2006;55:799-802 pubmed
    ..The percentages of atypical lymphocytes and total lymphocytes on a complete blood count provide another specific and moderately sensitive, yet inexpensive, test (SOR: C, based on validating cohort study)...
  22. Manez R, Domenech N, Centeno A, Lopez Pelaez E, Crespo F, Juffe A, et al. Failure to deplete anti-Galalpha1-3Gal antibodies after pig-to-baboon organ xenotransplantation by immunoaffinity columns containing multiple Galalpha1-3Gal oligosaccharides. Xenotransplantation. 2004;11:408-15 pubmed
    ..The increase in anti-alphaGal IgM after Tx was similar for the different antibodies of the anti-alphaGal polymorphism, and was only partially neutralized in vitro with the specific alphaGal oligosaccharide. ..
  23. Modjtahedi H, Hickish T, Nicolson M, Moore J, Styles J, Eccles S, et al. Phase I trial and tumour localisation of the anti-EGFR monoclonal antibody ICR62 in head and neck or lung cancer. Br J Cancer. 1996;73:228-35 pubmed
    ..On the basis of these data we conclude that MAb ICR62 can be administered safely to patients with squamous cell carcinomas and that it can localise efficiently to metastases even at relatively low doses. ..
  24. Kearns Jonker M, Fischer Lougheed J, Shulkin I, Kleihauer A, Mitsuhashi N, Kohn D, et al. Use of lentiviral vectors to induce long-term tolerance to gal(+) heart grafts. Transplantation. 2004;77:1748-54 pubmed
    ..Transduction with lentiviral vectors results in long-term, stable chimerism at levels sufficient to induce long-term tolerance to heart grafts in mice. ..
  25. Gomez M, Nieto J, Escribano M. Evaluation of two slide agglutination tests and a novel immunochromatographic assay for rapid diagnosis of infectious mononucleosis. Clin Diagn Lab Immunol. 2000;7:840-1 pubmed
    ..The specificities ranged from 86 to 100% in both age groups. These tests have a poor sensitivity for the diagnosis of IM, particularly in children. ..
  26. Everett M, Lin S, Worrell S, Platt J, Parker W. The footprint of antibody bound to pig cells: evidence of complex surface topology. Biochem Biophys Res Commun. 2003;301:751-7 pubmed
  27. Brandl U, Erhardt M, Michel S, Jöckle H, Burdorf L, Bittmann I, et al. Soluble Galalpha(1,3)Gal conjugate combined with hDAF preserves morphology and improves function of cardiac xenografts. Xenotransplantation. 2007;14:323-32 pubmed
    ..Due to an immediate and profound reduction in Galalpha(1,3)Gal-specific antibodies, soluble Galalpha(1,3)Gal conjugates not only prolong survival, but also improve the hemodynamic performance of the heart in DAF pigs. ..
  28. Lilienfeld B, Crew M, Forte P, Baumann B, Seebach J. Transgenic expression of HLA-E single chain trimer protects porcine endothelial cells against human natural killer cell-mediated cytotoxicity. Xenotransplantation. 2007;14:126-34 pubmed
  29. You S, Gouin E, Sai P. Feeding NOD mice with pig splenocytes induces transferable mechanisms that modulate cellular and humoral xenogeneic reactions against pig spleen or islet cells. Clin Exp Immunol. 2002;127:412-22 pubmed
    ..Decreased responsiveness may be due to active suppression, even though induction of anergy or deletion cannot be excluded. ..
  30. Kim W, Laterza O, Hock K, Pierson Perry J, Kaminski D, Mesguich M, et al. Performance of a revised cardiac troponin method that minimizes interferences from heterophilic antibodies. Clin Chem. 2002;48:1028-34 pubmed
    ..The revised Dimension cTnI method greatly minimizes the effect of interfering HAs. It also exhibits analytical performance characteristics consistent with recent guidelines for use of this assay to detect cardiac damage. ..
  31. Rood P, Rood P, Hara H, Busch J, Ezzelarab M, Zhu X, et al. Incidence and cytotoxicity of antibodies in cynomolgus monkeys directed to nonGal antigens, and their relevance for experimental models. Transpl Int. 2006;19:158-65 pubmed
  32. Brenner P, Schmoeckel M, Wimmer C, Eder V, Rucker A, Felbinger T, et al. Mean xenograft survival of 14.6 days in a small group of hDAF-transgenic pig hearts transplanted orthotopically into baboons. Transplant Proc. 2005;37:472-6 pubmed
    ..An optimum "fine-tuning" of immunosuppression is required to achieve the best risk-benefit ratio. ..
  33. Nyberg S, Amiot B, Hardin J, Baskin Bey E, Platt J. Cytotoxic immune response to a xenogeneic bioartificial liver. Cell Transplant. 2004;13:783-91 pubmed
    ..We conclude that antibody-mediated cytotoxicity contributed to the death of hepatocytes during treatment with a xenogeneic BAL. Immune-mediated death of hepatocytes was reduced by increasing selectivity of the BAL membrane. ..
  34. Swaggerty C, Pevzner I, He H, Genovese K, Nisbet D, Kaiser P, et al. Selection of broilers with improved innate immune responsiveness to reduce on-farm infection by foodborne pathogens. Foodborne Pathog Dis. 2009;6:777-83 pubmed publisher
    ..Utilization of pathogen-resistant birds by the poultry production industry would significantly enhance the microbiological safety of poultry products reaching the consumer. ..
  35. Vriens P, Stoot J, van der Steenhoven T, Hoyt G, Bouwman E, Robbins R. Pre-transplant blood transfusion and cyclosporin A induce long-term hamster cardiac xenograft survival in immunocompetent rats. Xenotransplantation. 2005;12:63-71 pubmed
    ..Combination of HBT with CSA treatment leads to long-term Xg survival in Lewis rats, whereas HBT alone results in HAR. The presence of T cells has a dominant influence on Xg survival after pre-transplant blood transfusion. ..
  36. Sivapurapu N, Hasegawa A, Gahlay G, Koyama K, Gupta S. Efficacy of antibodies against a chimeric synthetic peptide encompassing epitopes of bonnet monkey (Macaca radiata) zona pellucida-1 and zona pellucida-3 glycoproteins to inhibit in vitro human sperm-egg binding. Mol Reprod Dev. 2005;70:247-54 pubmed
    ..These studies have demonstrated that the chimeric peptide encompassing peptides of multiple ZP glycoproteins may be a promising candidate antigen for designing immunocontraceptive vaccines. ..
  37. Case C, Mooradian A. Elevated plasma chromogranin A levels attributable to assay interference: a source of diagnostic confusion. Endocr Pract. 2006;12:476-7 pubmed
  38. Ward G, Hickman P. Phantoms in the assay tube. J Clin Endocrinol Metab. 2004;89:433; author reply 433 pubmed
  39. Gołaszewska E, Kurowska E, Duk M, Koscielak J. Paul-Bunnell antigen and a possible mechanism of formation of heterophile antibodies in patients with infectious mononucleosis. Acta Biochim Pol. 2003;50:1205-11 pubmed
    ..6: 305). In conclusion, we present a hypothesis that anti-PB antibodies in patients with infectious mononucleosis are formed against infection-induced cell membrane glycoconjugates containing highly immunogenic Neu5Gc. ..
  40. Austin E, Smith L, Walker R. An anti-idiotopic antibody-based enzyme-linked immunosorbent assay for the quantification of the monoclonal anti-D BRAD-5. Vox Sang. 2001;80:179-83 pubmed
    ..The assay is reproducible with intra- and inter-assay coefficient of variation (CV) < 10%. This ELISA should prove of benefit in developing a monoclonal anti-D for prophylactic use. ..
  41. Bjerner J. Human anti-immunoglobulin antibodies interfering in immunometric assays. Scand J Clin Lab Invest. 2005;65:349-64 pubmed
  42. Cassin M, Cappelletti P, Rubin D, Zaninotto M, Macor F, Nicolosi G. [Two cases of false troponin I increase in patients with heterophile antibodies]. Ital Heart J Suppl. 2002;3:235-8 pubmed
  43. Macchiarini P, Oriol R, Azimzadeh A, de Montpreville V, Wolf P, Dartevelle P. Characterization of a pig-to-goat orthotopic lung xenotransplantation model to study beyond hyperacute rejection. J Thorac Cardiovasc Surg. 1999;118:805-14 pubmed
    ..Pig left lung xenografts can provide prolonged and complete respiratory support after depletion of goat xenoreactive antibodies, but they ultimately necrose once recipient xenoreactive antibodies return to pretransplantation values. ..
  44. Buhler L, Xu Y, Li W, Zhu A, Cooper D. An investigation of the specificity of induced anti-pig antibodies in baboons. Xenotransplantation. 2003;10:88-93 pubmed
    ..In this limited study, no Ab response to non-Gal carbohydrates was observed, and anti-SLA specificity was minor, indicating that most induced anti-non-Gal Ab was directed against non-specific pig proteins, including SLA-epitopes. ..
  45. Saini S, Kaushik A, Basrur P, Yamashiro S. Ultrastructural and immunologic characteristics of mouse x cattle xenogeneic hybridomas originating from bovine leukemia virus-infected cattle. Vet Pathol. 2003;40:460-4 pubmed
    ..Presence of c-type particles in hybridomas suggests that T cell-derived cytokines are not required for sustained BLV expression. ..
  46. Arbel M, Lavie V, Solomon B. Generation of antibodies against prion protein in wild-type mice via helix 1 peptide immunization. J Neuroimmunol. 2003;144:38-45 pubmed
    ..The generated antibodies recognize the whole prion protein with a high binding constant and the established protocol may lead to an active immunization towards therapeutics of prion disease. ..
  47. Platt J. The prospects for xenotransplantation of the kidney. Curr Opin Nephrol Hypertens. 1997;6:284-91 pubmed
    ..The past few years have brought considerable progress in elucidating the molecular and cellular basis of xenograft rejection and in developing strategies to overcome it. ..
  48. O Donnell R, Shen S, Denardo S, Wun T, Kukis D, Goldstein D, et al. A phase I study of 90Y-2IT-BAD-Lym-1 in patients with non-Hodgkin's lymphoma. Anticancer Res. 2000;20:3647-55 pubmed
    ..90Y-2IT-BAD-Lym-1 may be useful for future clinical trials because 90Y is readily available and can deliver potent beta emissions to NHL. Bone marrow support however, will be required for further dose escalation. ..
  49. van Toorenenbergen A, Hooijkaas H, Heerenbrink G, Dufour van den Goorbergh D. Heterophilic antibody interference in a tryptase immunoassay. Clin Biochem. 2008;41:331-4 pubmed
    ..The Phadia tryptase assay method, in its present form, is sensitive to interference by heterophilic antibodies. ..
  50. Ivanovski P, Ivanovski I, Sedlarevic R. Are xenogeneic anti-tissue transglutaminase antibodies the holy grail for celiac patients?. Med Hypotheses. 2007;69:1257-60 pubmed
  51. Wellhausen S, Slone S, Miller J. Clone-specific anti-CD45 blocking factor in patient plasma. Cytometry B Clin Cytom. 2007;72:423-6 pubmed
    ..Biochemical identification of blocking factor was not accomplished. ..
  52. Diaz I, Veira P, Valdes F, Alonso C, Sanchez P. Quantitation and comparison of anti-Gal-alpha-1,3-Gal antibodies in sera of healthy individuals and patients waiting for kidney transplantation. Transplant Proc. 2003;35:2043-4 pubmed
    ..Thus, sensitized patients do not present a greater risk of rejection or are more difficult to treat for natural xenoreactivity than nonsensitized patients. ..
  53. Choe K, O Brien S, Evans D, Toop T, Edwards S. Immunolocalization of Na+/K+-ATPase, carbonic anhydrase II, and vacuolar H+-ATPase in the gills of freshwater adult lampreys, Geotria australis. J Exp Zool A Comp Exp Biol. 2004;301:654-65 pubmed
    ..A model of ion transport, based on our results, is proposed for adult freshwater lampreys. ..