Skip to main content
Erschienen in: Journal of Clinical Immunology 2/2010

01.03.2010

Natural Hidden Autoantibodies to Tissue Transglutaminase Cross-React with Fibrinogen

verfasst von: Ingrid M. Zöller-Utz, Birgit Esslinger, Anja Schulze-Krebs, Walburga Dieterich

Erschienen in: Journal of Clinical Immunology | Ausgabe 2/2010

Einloggen, um Zugang zu erhalten

Abstract

Introduction

Patients with celiac disease display autoantibodies against tissue transglutaminase (TG2), and the high sensitivity and specificity of these autoantibodies render them a reliable tool for diagnosis. However, we found that denatured sera from healthy persons also showed reactivity against TG2.

Methods

To further examine the specificity of this phenomenon, sera of healthy individuals and celiac patients were denatured by heat or pH shift.

Results and discussion

Denatured sera of all individuals showed autoantibodies against TG2 in ELISA that could be specifically inhibited by TG2, but the biological role of these autoantibodies remains unknown. The alpha fibrinogen precursor could be isolated as serum protein that reacts with TG2 antibodies and treated sera reacted with fibrinogen in Western blotting. Cross-reactivity of TG2 antibodies with fibrinogen and vice versa was observed.

Conclusion

We hypothesise that denaturation of sera reveals hidden autoantibodies against TG2, which might be normally masked by fibrinogen.
Literatur
2.
Zurück zum Zitat Marsh MN. Gluten, major histocompatibility complex, and the small intestine. A molecular and immunobiologic approach to the spectrum of gluten sensitivity (‘celiac sprue’). Gastroenterology. 1992;102:330–54. PubMed Marsh MN. Gluten, major histocompatibility complex, and the small intestine. A molecular and immunobiologic approach to the spectrum of gluten sensitivity (‘celiac sprue’). Gastroenterology. 1992;102:330–54. PubMed
3.
4.
Zurück zum Zitat Catassi C, Kryszak D, Louis-Jacques O, Duerksen DR, Hill I, Crowe SE, et al. Detection of Celiac disease in primary care: a multicenter case-finding study in North America. Am J Gastroenterol. 2007;102:1454–60. CrossRefPubMed Catassi C, Kryszak D, Louis-Jacques O, Duerksen DR, Hill I, Crowe SE, et al. Detection of Celiac disease in primary care: a multicenter case-finding study in North America. Am J Gastroenterol. 2007;102:1454–60. CrossRefPubMed
5.
Zurück zum Zitat Dube C, Rostom A, Sy R, Cranney A, Saloojee N, Garritty C, et al. The prevalence of celiac disease in average-risk and at-risk Western European populations: a systematic review. Gastroenterology. 2005;128:S57–67. CrossRefPubMed Dube C, Rostom A, Sy R, Cranney A, Saloojee N, Garritty C, et al. The prevalence of celiac disease in average-risk and at-risk Western European populations: a systematic review. Gastroenterology. 2005;128:S57–67. CrossRefPubMed
6.
Zurück zum Zitat Guandalini S. The influence of gluten: weaning recommendations for healthy children and children at risk for celiac disease. Nestle Nutr Workshop Ser Pediatr Program. 2007;60:139–51. discussion 151-135. CrossRefPubMed Guandalini S. The influence of gluten: weaning recommendations for healthy children and children at risk for celiac disease. Nestle Nutr Workshop Ser Pediatr Program. 2007;60:139–51. discussion 151-135. CrossRefPubMed
7.
Zurück zum Zitat Norris JM, Barriga K, Hoffenberg EJ, Taki I, Miao D, Haas JE, et al. Risk of celiac disease autoimmunity and timing of gluten introduction in the diet of infants at increased risk of disease. JAMA. 2005;293:2343–51. CrossRefPubMed Norris JM, Barriga K, Hoffenberg EJ, Taki I, Miao D, Haas JE, et al. Risk of celiac disease autoimmunity and timing of gluten introduction in the diet of infants at increased risk of disease. JAMA. 2005;293:2343–51. CrossRefPubMed
8.
Zurück zum Zitat Carlsson A, Agardh D, Borulf S, Grodzinsky E, Axelsson I, Ivarsson SA. Prevalence of celiac disease: before and after a national change in feeding recommendations. Scand J Gastroenterol. 2006;41:553–8. CrossRefPubMed Carlsson A, Agardh D, Borulf S, Grodzinsky E, Axelsson I, Ivarsson SA. Prevalence of celiac disease: before and after a national change in feeding recommendations. Scand J Gastroenterol. 2006;41:553–8. CrossRefPubMed
9.
Zurück zum Zitat Stene LC, Honeyman MC, Hoffenberg EJ, Haas JE, Sokol RJ, Emery L, et al. Rotavirus infection frequency and risk of celiac disease autoimmunity in early childhood: a longitudinal study. Am J Gastroenterol. 2006;101:2333–40. CrossRefPubMed Stene LC, Honeyman MC, Hoffenberg EJ, Haas JE, Sokol RJ, Emery L, et al. Rotavirus infection frequency and risk of celiac disease autoimmunity in early childhood: a longitudinal study. Am J Gastroenterol. 2006;101:2333–40. CrossRefPubMed
10.
Zurück zum Zitat Troncone R, Auricchio S. Rotavirus and celiac disease: clues to the pathogenesis and perspectives on prevention. J Pediatr Gastroenterol Nutr. 2007;44:527–8. CrossRefPubMed Troncone R, Auricchio S. Rotavirus and celiac disease: clues to the pathogenesis and perspectives on prevention. J Pediatr Gastroenterol Nutr. 2007;44:527–8. CrossRefPubMed
11.
12.
Zurück zum Zitat Dieterich W, Ehnis T, Bauer M, Donner P, Volta U, Riecken EO, et al. Identification of tissue transglutaminase as the autoantigen of celiac disease. Nat Med. 1997;3:797–801. CrossRefPubMed Dieterich W, Ehnis T, Bauer M, Donner P, Volta U, Riecken EO, et al. Identification of tissue transglutaminase as the autoantigen of celiac disease. Nat Med. 1997;3:797–801. CrossRefPubMed
13.
Zurück zum Zitat Dieterich W, Laag E, Schopper H, Volta U, Ferguson A, Gillett H, et al. Autoantibodies to tissue transglutaminase as predictors of celiac disease. Gastroenterology. 1998;115:1317–21. CrossRefPubMed Dieterich W, Laag E, Schopper H, Volta U, Ferguson A, Gillett H, et al. Autoantibodies to tissue transglutaminase as predictors of celiac disease. Gastroenterology. 1998;115:1317–21. CrossRefPubMed
14.
Zurück zum Zitat Wong RC, Wilson RJ, Steele RH, Radford-Smith G, Adelstein S. A comparison of 13 guinea pig and human anti-tissue transglutaminase antibody ELISA kits. J Clin Pathol. 2002;55:488–94. PubMed Wong RC, Wilson RJ, Steele RH, Radford-Smith G, Adelstein S. A comparison of 13 guinea pig and human anti-tissue transglutaminase antibody ELISA kits. J Clin Pathol. 2002;55:488–94. PubMed
15.
Zurück zum Zitat Brownlee AA, Lockwood CM. Heat treatment of normal human sera reveals antibodies to bactericidal permeability-inducing protein (BPI). Clin Exp Immunol. 1999;117:183–9. CrossRefPubMed Brownlee AA, Lockwood CM. Heat treatment of normal human sera reveals antibodies to bactericidal permeability-inducing protein (BPI). Clin Exp Immunol. 1999;117:183–9. CrossRefPubMed
16.
Zurück zum Zitat Cancado EL, Abrantes-Lemos CP, Vilas-Boas LS, Novo NF, Carrilho FJ, Laudanna AA. Thermolabile and calcium-dependent serum factor interferes with polymerized actin, and impairs anti-actin antibody detection. J Autoimmun. 2001;17:223–8. CrossRefPubMed Cancado EL, Abrantes-Lemos CP, Vilas-Boas LS, Novo NF, Carrilho FJ, Laudanna AA. Thermolabile and calcium-dependent serum factor interferes with polymerized actin, and impairs anti-actin antibody detection. J Autoimmun. 2001;17:223–8. CrossRefPubMed
17.
Zurück zum Zitat Soltis RD, Hasz D, Morris MJ, Wilson ID. The effect of heat inactivation of serum on aggregation of immunoglobulins. Immunology. 1979;36:37–45. PubMed Soltis RD, Hasz D, Morris MJ, Wilson ID. The effect of heat inactivation of serum on aggregation of immunoglobulins. Immunology. 1979;36:37–45. PubMed
18.
Zurück zum Zitat D'Cruz DP, Keser G, Direskeneli H, Khamashta MA, Hughes GR. Anti-endothelial cell antibodies in systemic vasculitis and systemic lupus erythematosus (SLE): effects of heat inactivation on binding and specificity. Clin Exp Immunol. 1999;115:567–70. CrossRefPubMed D'Cruz DP, Keser G, Direskeneli H, Khamashta MA, Hughes GR. Anti-endothelial cell antibodies in systemic vasculitis and systemic lupus erythematosus (SLE): effects of heat inactivation on binding and specificity. Clin Exp Immunol. 1999;115:567–70. CrossRefPubMed
19.
Zurück zum Zitat Jungkind DL, DiRenzo SA, Young SJ. Effect of using heat-inactivated serum with the Abbott human T-cell lymphotropic virus type III antibody test. J Clin Microbiol. 1986;23:381–2. PubMed Jungkind DL, DiRenzo SA, Young SJ. Effect of using heat-inactivated serum with the Abbott human T-cell lymphotropic virus type III antibody test. J Clin Microbiol. 1986;23:381–2. PubMed
20.
Zurück zum Zitat Hasselaar P, Triplett DA, LaRue A, Derksen RH, Blokzijl L, de Groot PG, et al. Heat treatment of serum and plasma induces false positive results in the antiphospholipid antibody ELISA. J Rheumatol. 1990;17:186–91. PubMed Hasselaar P, Triplett DA, LaRue A, Derksen RH, Blokzijl L, de Groot PG, et al. Heat treatment of serum and plasma induces false positive results in the antiphospholipid antibody ELISA. J Rheumatol. 1990;17:186–91. PubMed
21.
Zurück zum Zitat Cheng HM, Ngeow YF, Sam CK. Heat inactivation of serum potentiates anti-cardiolipin antibody binding in ELISA. J Immunol Methods. 1989;124:235–8. CrossRefPubMed Cheng HM, Ngeow YF, Sam CK. Heat inactivation of serum potentiates anti-cardiolipin antibody binding in ELISA. J Immunol Methods. 1989;124:235–8. CrossRefPubMed
22.
Zurück zum Zitat Cheng HM, Chamley L. Cryptic natural autoantibodies and co-potentiators. Autoimmun Rev. 2008;7:431–4. CrossRefPubMed Cheng HM, Chamley L. Cryptic natural autoantibodies and co-potentiators. Autoimmun Rev. 2008;7:431–4. CrossRefPubMed
23.
Zurück zum Zitat Cheng HM. Antiphospholipid antibodies are masked in normal human serum. Immunol Today. 1991;12:96. CrossRefPubMed Cheng HM. Antiphospholipid antibodies are masked in normal human serum. Immunol Today. 1991;12:96. CrossRefPubMed
24.
Zurück zum Zitat Dieterich W, Trapp D, Esslinger B, Leidenberger M, Piper J, Hahn E, et al. Autoantibodies of patients with coeliac disease are insufficient to block tissue transglutaminase activity. Gut. 2003;52:1562–6. CrossRefPubMed Dieterich W, Trapp D, Esslinger B, Leidenberger M, Piper J, Hahn E, et al. Autoantibodies of patients with coeliac disease are insufficient to block tissue transglutaminase activity. Gut. 2003;52:1562–6. CrossRefPubMed
25.
Zurück zum Zitat Agardh D, Roth B, Lernmark A, Stenberg P. Calcium activation of tissue transglutaminase in radioligand binding and enzyme-linked autoantibody immunoassays in childhood celiac disease. Clin Chim Acta. 2005;358:95–103. CrossRefPubMed Agardh D, Roth B, Lernmark A, Stenberg P. Calcium activation of tissue transglutaminase in radioligand binding and enzyme-linked autoantibody immunoassays in childhood celiac disease. Clin Chim Acta. 2005;358:95–103. CrossRefPubMed
26.
Zurück zum Zitat Griffin M, Casadio R, Bergamini CM. Transglutaminases: nature's biological glues. Biochem J. 2002;368:377–96. CrossRefPubMed Griffin M, Casadio R, Bergamini CM. Transglutaminases: nature's biological glues. Biochem J. 2002;368:377–96. CrossRefPubMed
27.
Zurück zum Zitat Mitkevich OV, Shainoff JR, DiBello PM, Yee VC, Teller DC, Smejkal GB, et al. Coagulation factor XIIIa undergoes a conformational change evoked by glutamine substrate. Studies on kinetics of inhibition and binding of XIIIA by a cross-reacting antifibrinogen antibody. J Biol Chem. 1998;273:14387–91. CrossRefPubMed Mitkevich OV, Shainoff JR, DiBello PM, Yee VC, Teller DC, Smejkal GB, et al. Coagulation factor XIIIa undergoes a conformational change evoked by glutamine substrate. Studies on kinetics of inhibition and binding of XIIIA by a cross-reacting antifibrinogen antibody. J Biol Chem. 1998;273:14387–91. CrossRefPubMed
28.
Zurück zum Zitat Bussone G, Dib H, Dimitrov JD, Camoin L, Broussard C, Tamas N, et al. Identification of target antigens of self-reactive IgG in intravenous immunoglobulin preparations. Proteomics. 2009;9:2253–62. CrossRefPubMed Bussone G, Dib H, Dimitrov JD, Camoin L, Broussard C, Tamas N, et al. Identification of target antigens of self-reactive IgG in intravenous immunoglobulin preparations. Proteomics. 2009;9:2253–62. CrossRefPubMed
29.
Zurück zum Zitat Djoumerska I, Tchorbanov A, Pashov A, Vassilev T. The autoreactivity of therapeutic intravenous immunoglobulin (IVIG) preparations depends on the fractionation methods used. Scand J Immunol. 2005;61:357–63. CrossRefPubMed Djoumerska I, Tchorbanov A, Pashov A, Vassilev T. The autoreactivity of therapeutic intravenous immunoglobulin (IVIG) preparations depends on the fractionation methods used. Scand J Immunol. 2005;61:357–63. CrossRefPubMed
30.
Zurück zum Zitat Dimitrov JD, Lacroix-Desmazes S, Kaveri SV, Vassilev TL. Transition towards antigen-binding promiscuity of a monospecific antibody. Mol Immunol. 2007;44:1854–63. CrossRefPubMed Dimitrov JD, Lacroix-Desmazes S, Kaveri SV, Vassilev TL. Transition towards antigen-binding promiscuity of a monospecific antibody. Mol Immunol. 2007;44:1854–63. CrossRefPubMed
31.
Zurück zum Zitat Labrousse H, Adib-Conquy M, Avrameas S. Effect of temperature on the reactivities of polyreactive and monospecific monoclonal IgG antibodies. Res Immunol. 1997;148:267–76. CrossRefPubMed Labrousse H, Adib-Conquy M, Avrameas S. Effect of temperature on the reactivities of polyreactive and monospecific monoclonal IgG antibodies. Res Immunol. 1997;148:267–76. CrossRefPubMed
32.
Zurück zum Zitat Abu-Shakra M, Shoenfeld Y. Natural hidden autoantibodies. Isr Med Assoc J. 2007;9:748–9. PubMed Abu-Shakra M, Shoenfeld Y. Natural hidden autoantibodies. Isr Med Assoc J. 2007;9:748–9. PubMed
33.
Zurück zum Zitat Kra-Oz Z, Lorber M, Shoenfeld Y, Scharff Y. Inhibitor(s) of natural anti-cardiolipin autoantibodies. Clin Exp Immunol. 1993;93:265–8. PubMedCrossRef Kra-Oz Z, Lorber M, Shoenfeld Y, Scharff Y. Inhibitor(s) of natural anti-cardiolipin autoantibodies. Clin Exp Immunol. 1993;93:265–8. PubMedCrossRef
34.
Zurück zum Zitat Druet E, Praddaude F, Druet P, Dietrich G. Non-immunoglobulin serum proteins prevent the binding of IgG from normal rats and from rats with Th2-mediated autoimmune glomerulonephritis to various autoantigens including glomerular antigens. Eur J Immunol. 1998;28:183–92. CrossRefPubMed Druet E, Praddaude F, Druet P, Dietrich G. Non-immunoglobulin serum proteins prevent the binding of IgG from normal rats and from rats with Th2-mediated autoimmune glomerulonephritis to various autoantigens including glomerular antigens. Eur J Immunol. 1998;28:183–92. CrossRefPubMed
35.
Zurück zum Zitat McIntyre JA, Hamilton RL, DeKosky ST. Redox-reactive autoantibodies in cerebrospinal fluids. Ann N Y Acad Sci. 2007;1109:296–302. CrossRefPubMed McIntyre JA, Hamilton RL, DeKosky ST. Redox-reactive autoantibodies in cerebrospinal fluids. Ann N Y Acad Sci. 2007;1109:296–302. CrossRefPubMed
36.
Zurück zum Zitat Omersel J, Jurgec I, Cucnik S, Kveder T, Rozman B, Sodin-Semrl S, et al. Autoimmune and proinflammatory activity of oxidized immunoglobulins. Autoimmun Rev. 2008;7:523–9. CrossRefPubMed Omersel J, Jurgec I, Cucnik S, Kveder T, Rozman B, Sodin-Semrl S, et al. Autoimmune and proinflammatory activity of oxidized immunoglobulins. Autoimmun Rev. 2008;7:523–9. CrossRefPubMed
37.
Zurück zum Zitat McIntyre JA, Faulk WP. Redox-reactive autoantibodies: biochemistry, characterization, and specificities. Clin Rev Allergy Immunol. 2009;37:49–54. CrossRefPubMed McIntyre JA, Faulk WP. Redox-reactive autoantibodies: biochemistry, characterization, and specificities. Clin Rev Allergy Immunol. 2009;37:49–54. CrossRefPubMed
38.
Zurück zum Zitat McIntyre JA, Wagenknecht DR, Faulk WP. Autoantibodies unmasked by redox reactions. J Autoimmun. 2005;24:311–7. CrossRefPubMed McIntyre JA, Wagenknecht DR, Faulk WP. Autoantibodies unmasked by redox reactions. J Autoimmun. 2005;24:311–7. CrossRefPubMed
39.
Zurück zum Zitat McIntyre JA, Wagenknecht DR, Faulk WP. Redox-reactive autoantibodies: detection and physiological relevance. Autoimmun Rev. 2006;5:76–83. CrossRefPubMed McIntyre JA, Wagenknecht DR, Faulk WP. Redox-reactive autoantibodies: detection and physiological relevance. Autoimmun Rev. 2006;5:76–83. CrossRefPubMed
Metadaten
Titel
Natural Hidden Autoantibodies to Tissue Transglutaminase Cross-React with Fibrinogen
verfasst von
Ingrid M. Zöller-Utz
Birgit Esslinger
Anja Schulze-Krebs
Walburga Dieterich
Publikationsdatum
01.03.2010
Verlag
Springer US
Erschienen in
Journal of Clinical Immunology / Ausgabe 2/2010
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-009-9347-z

Weitere Artikel der Ausgabe 2/2010

Journal of Clinical Immunology 2/2010 Zur Ausgabe

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.