Levels and avidities of antiphosphatidylethanolamine antibodies in patients with thrombotic events and immunologically-mediated diseases.
Oliver Kuchar, Milada Petrackova, Marta Kalousova, Libuse Noskova, Tomas Zima, Lenka Fialova
Author Information
Oliver Kuchar: Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic.
Milada Petrackova: Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic.
Marta Kalousova: Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic.
Libuse Noskova: Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic.
Tomas Zima: Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic.
Lenka Fialova: Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic.
AIMS: Antiphosphatidylethanolamine antibodies (aPE) represent one type of antiphospholipid antibody (aPL) directed against the neutral phospholipids - phosphatidylethanolamines. The aim of this study was to evaluate levels and avidities of aPE in several groups of patients and compare them with conventional aPLs. METHODS: aPE were analysed in a cohort consisting of 68 hospitalized patients. The other cohort comprised 22 patients with immunologically-mediated diseases. The control group consisted of 20 healthy persons. ELISA methods were used for determination of aPL. Avidities of aPE were tested by modified ELISA with urea as a chaotropic agent. RESULTS: aPE IgG/IgM were significantly higher in the group of patients with venous thromboembolism than those with non-thrombotic internal disorders (P=0.02 for both Ig classes). aPE IgG/IgM elevated above cut-off values were found in 10.8% of patients with venous thromboembolism and as a single aPL in 6.5%. Levels of aPE IgG higher than our limit (>6 U/mL) were detected in 29% of patients with immunologically-mediated diseases with other positive aPL. Low-, intermediate- and high-avidity aPE IgG were found in patients of both cohorts. The avidities of aPE IgG differed from those of anticardiolipin antibodies IgG. Neither aPE IgG levels nor avidity dynamics significantly changed during follow-up. CONCLUSION: aPE may be related to venous thromboembolism and may be part of the repertoire of aPL in immunologically-mediated diseases. There are patients with thrombosis negative for conventional aPL but positive for aPE. aPE IgG may have different avidities.
Misasi R, Capozzi A, Longo A, Recalchi S, Lococo E, Alessandri C, Conti F, Valesini G, Sorice M. "New" antigenic targets and methodological approaches for refining laboratory diagnosis of antiphospholipid syndrome. J Immunol Res 2015;2015:858542.
[DOI: 10.1155/2015/858542]
Hughes GR. Thrombosis, abortion, cerebral disease, and the lupus anticoagulant. Br Med J (Clin Res Ed) 1983;287:1088-9.
[PMID: 6414579]
Schreiber K, Sciascia S, de Groot PG, Devreese K, Jacobsen S, Ruiz-Irastorza G, Salmon JE, Shoenfeld Y, Shovman O, Hunt BJ. Antiphospholipid syndrome. Nat Rev Dis Primers 2018;4:17103.
[PMID: 29321641]
Devreese KMJ, Ortel TL, Pengo V, de Laat B. Subcommittee on Lupus Anticoagulant/Antiphospholipid A. Laboratory criteria for antiphospholipid syndrome: communication from the SSC of the ISTH. J Thromb Haemost 2018;16:809-13.
[DOI: 10.1111/jth.14238]
Devreese KMJ. How to Interpret Antiphospholipid Laboratory Tests. Curr Rheumatol Rep 2020;22:38.
[PMID: 32562091]
Bradacova P, Slavik L, Ulehlova J, Skoumalova A, Ullrychova J, Prochazkova J, Hlusi A, Manukyan G, Kriegova E. Current Promising Biomarkers and Methods in the Diagnostics of Antiphospholipid Syndrome: A Review. Biomedicines 2021;9:166.
[DOI: 10.3390/biomedicines9020166]
Zigon P, Podovsovnik A, Ambrozic A, Tomsic M, Hocevar A, Gaspersic N, Rotar Z, Praprotnik S, Semrl SS, Cucnik S. Added value of non-criteria antiphospholipid antibodies for antiphospholipid syndrome: lessons learned from year-long routine measurements. Clin Rheumatol 2019;38:371-8.
[PMID: 30099654]
Tonello M, Mattia E, Favaro M, Del Ross T, Calligaro A, Salvan E, Hoxha A, Fedrigo M, Ruffatti A. IgG phosphatidylserine/prothrombin antibodies as a risk factor of thrombosis in antiphospholipid antibody carriers. Thromb Res 2019;177:157-60.
[DOI: 10.1016/j.thromres.2019.03.006]
Staub HL, Bertolaccini ML, Khamashta MA. Anti-phosphatidylethanolamine antibody, thromboembolic events and the antiphospholipid syndrome. Autoimmun Rev 2012;12:230-4.
[PMID: 22796282]
Vance JE. Phosphatidylserine and phosphatidylethanolamine in mammalian cells: two metabolically related aminophospholipids. J Lipid Res 2008;49:1377-87.
[DOI: 10.1194/jlr.R700020-JLR200]
Zhixin L, Wells CW, North PE, Kumar S, Duris CB, McIntyre JA, Ming Z. Phosphatidylethanolamine at the luminal endothelial surface-implications for hemostasis and thrombotic autoimmunity. Clin Appl Thromb Hemost 2011;17:158-63.
[DOI: 10.1177/1076029609350620]
Butkiewicz F, Kaszuba M, Brzezinski M, Izbicki J, Kubis M, Lopinski H, Borowiak M, Szelepajlo M, Fischer K, Flicinski J. Associations between the incidence of antiphosphatidylserine and antiphosphatidylethanolamine antibodies and clinical manifestations of systemic lupus erythematosus. Pol Arch Med Wewn 2014;124:573-8.
[PMID: 25220366]
Dima A, Caraiola S, Jurcut C, Balanescu E, Balanescu P, Ramba D, Badea C, Pompilian V, Ionescu R, Baicus A, Baicus C, Dan GA. Extended Antiphospholipid Antibodies Screening in Systemic Lupus Erythematosus Patients. Rom J Intern Med 2015;53:321-8.
[DOI: 10.1515/rjim-2015-0041]
Caraiola S, Jurcut C, Dima A, Baicus C, Baicus A. Antiphosphatidylethanolamine Antibodies and Deep Vein Thrombosis in Lupus Patients with Antiphospholipid Syndrome. Revista Romana De Medicina De Laborator 2018;26:243-50.
[DOI: 10.2478/rrlm-2018-0009]
Fialova L. Avidity of antiphospholipid antibodies - our current knowledge. Epidemiol Mikrobiol Imunol 2014;63:221-5.
Fialova L, Petrackova M, Kuchar O. Comparison of different enzyme-linked immunosorbent assay methods for avidity determination of antiphospholipid antibodies. J Clin Lab Anal 2017;31:e22121.
[DOI: 10.1002/jcla.22121]
Fialova L, Malbohan I, Malickova K. Avidity of anticardiolipin antibodies-A factor that could be important for their detection by ELISA methods. J Appl Biomed 2014;12:277-84.
[DOI: 10.1016/j.jab.2014.01.005]
Almanzar G, Ottensmeier B, Liese J, Prelog M. Assessment of IgG avidity against pertussis toxin and filamentous hemagglutinin via an adapted enzyme-linked immunosorbent assay (ELISA) using ammonium thiocyanate. J Immunol Methods 2013;387:36-42.
[DOI: 10.1016/j.jim.2012.09.008]
Prince HE, Lape-Nixon M. Role of cytomegalovirus (CMV) IgG avidity testing in diagnosing primary CMV infection during pregnancy. Clin Vaccine Immunol 2014;21:1377-84.
[PMID: 25165026]
Ozarda Y. Reference intervals: current status, recent developments and future considerations. Biochem Med (Zagreb) 2016;26:5-16.
[PMID: 26981015]
Dimitrov JD, Lacroix-Desmazes S, Kaveri SV. Important parameters for evaluation of antibody avidity by immunosorbent assay. Anal Biochem 2011;418:149-51.
[PMID: 21803020]
Fialová L, Kuchař O, Petráčkova M, Malbohan I, Zima T. Avidity of anti-phospholipid antibodies in relation to their levels. Cent Eur J Immunol 2020;45:136-43.
[DOI: 10.5114/ceji.2020.97901]
Sanmarco M, Gayet S, Alessi MC, Audrain M, de Maistre E, Gris JC, de Groot PG, Hachulla E, Harle JR, Sie P, Boffa MC. Antiphosphatidylethanolamine antibodies are associated with an increased odds ratio for thrombosis. A multicenter study with the participation of the European Forum on antiphospholipid antibodies. Thromb Haemost 2007;97:949-54.
[PMID: 17549297]
Sanmarco M, Alessi MC, Harle JR, Sapin C, Aillaud MF, Gentile S, Juhan-Vague I, Weiller PJ. Antibodies to phosphatidylethanolamine as the only antiphospholipid antibodies found in patients with unexplained thromboses. Thromb Haemost 2001;85:800-5.
[PMID: 11372671]
Bertolaccini ML, Murru V, Sciascia S, Sanna G, Khamashta MA. The clinical value of testing for antibodies to phosphatidylethanolamine (aPE) in patients with systemic lupus erythematosus (SLE). Thromb Res 2012;130:914-8.
[DOI: 10.1016/j.thromres.2012.06.008]
Zhang S, Wu Z, Zhang W, Zhang F, Li Y, Liu Y. Clinical performance of non-criteria antibodies to phospholipids in Chinese patients with antiphospholipid syndrome. Clin Chim Acta 2019;495:205-9.
[DOI: 10.1016/j.cca.2019.04.065]
Sanmarco M. ELISA for antiphosphatidylethanolamine antibody detection: high impact of assay buffer on results. J Immunol Methods 2010;358:9-16.
[DOI: 10.1016/j.jim.2010.04.002]
Ke K, Strango ZI, Harper PE, Zhao M. Influence of Phosphatidylethanolamine Concentration and Composition on the Detection of Antiphosphatidylethanolamine Antibodies by ELISA. J Clin Lab Anal 2016;30:689-96.
[DOI: 10.1002/jcla.21923]
Vlachoyiannopoulos PG, Petrovas C, Tektonidou M, Krilis S, Moutsopoulos HM. Antibodies to beta 2-glycoprotein-I: urea resistance, binding specificity, and association with thrombosis. J Clin Immunol 1998;18:380-91.
[DOI: 10.1023/A]
Cucnik S, Kveder T, Artenjak A, Ulcova Gallova Z, Swadzba J, Musial J, Iwaniec T, Stojanovich L, Alessandri C, Valesini G, Avcin T, Cohen Tervaert JW, Rozman B, Bozic B. Avidity of anti-beta2-glycoprotein I antibodies in patients with antiphospholipid syndrome. Lupus 2012;21:764-5.
[PMID: 22635226]
Totland C, Aarseth J, Vedeler C. Hu and Yo antibodies have heterogeneous avidity. J Neuroimmunol 2007;185:162-7.
[DOI: 10.1016/j.jneuroim.2007.01.016]
Zeng Y, Lin Y, Wang X, Zhang Y, Peng F, Wang J, Jiang L, Liang S, Xiao Y. Assessment of a high-avidity IgG ANAs for the diagnosis and activity prediction of systemic lupus erythematosus. Clin Rheumatol 2020;39:2619-29.
[PMID: 32189150]
Jianping L, Zhibing Y, Wei Q, Zhikai C, Jie X, Jinbiao L. Low avidity and level of serum anti-Abeta antibodies in Alzheimer disease. Alzheimer Dis Assoc Disord 2006;20:127-32.
[PMID: 16917180]
