INTRODUCTION: The heterogeneity of anti-phospholipid antibodies can be manifested not only in different antigenic specificities, but also in their avidities. The aim of the study was to investigate the relationship between anti-cardiolipin antibody (aCL) IgG avidities and levels within the range of their titres, from very low to high ones. MATERIAL AND METHODS: We analyzed 78 serum samples from 60 patients by ELISA with chaotropic agents, using urea concentration of 6 and 8 mol/l and single diluted serum samples. The changes of aCL levels and avidities were explored during a long-term follow-up in 14 patients. RESULTS: The avidities of aCLs did not differ in the groups of patients classified according to aCL levels. The higher avidity antibodies predominated in our patients and the fluctuation of avidities in the longitudinal follow-up did not show significant differences. No relationship between aCL levels and their avidities was found. CONCLUSIONS: aCL avidities seem to have no relationship with aCL levels and high-avidity aCLs; the potentially deleterious effects might be present also in patients with low and extremely low aCL levels. Avidity of aCLs belongs to stable characteristics with insignificant changes in time.

Institute of Medical Biochemistry and Laboratory Diagnostics 1st Faculty of Medicine Charles University and General University Hospital Prague Czech Republic

Zobrazit více v PubMed

Misasi R, Capozzi A, Longo A, et al. (2015): “New” antigenic targets and methodological approaches for refining laboratory diagnosis of antiphospholipid syndrome. J Immunol Res 2015: 858542. PubMed PMC

Alessandri C, Conti F, Pendolino M, et al. (2011): New autoantigens in the antiphospholipid syndrome. Autoimmun Rev 10: 609-616. PubMed

Hughes GRV. (1983): Thrombosis, abortion, cerebral disease, and the lupus anticoagulant. Br Med J 287: 1088-1089. PubMed PMC

Hughes GRV. (2014): Hughes syndrome/APS. 30 years on, what have we learnt? Opening talk at the 14th International Congress on antiphospholipid antibodies Rio de Janiero, October 2013. Lupus 23: 400-406. PubMed

Nikolova-Vlahova MK, Nikolov KV, Baleva MP, et al. (2015): Antiphospholipid antibodies in patients with upper-extremity deep vein thrombosis. Cent Eur J Immunol 40: 307-310. PubMed PMC

Miyakis S, Lockshin MD, Atsumi T, et al. (2006): International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 4: 295-306. PubMed

Nayfe R, Uthman I, Aoun J, et al. (2013): Seronegative antiphospholipid syndrome. Rheumatology 52: 1358-1367. PubMed

Forastiero R. (2014): Multiple antiphospholipid antibodies positivity and antiphospholipid syndrome criteria re-evaluation. Lupus 23: 1252-1254. PubMed

Sciascia S, Radin M, Bazzan M, et al. (2017): Novel diagnostic and therapeutic frontiers in thrombotic anti-phospholipid syndrome. Intern Emerg Med 12: 1-7. PubMed

Bertolaccini ML, Amengual O, Atsumi T, et al. (2011): ‘Non-criteria’ aPL tests: report of a task force and preconference workshop at the 13th International Congress on Antiphospholipid Antibodies Galveston, TX, USA, April 2010. Lupus 20: 191-205. PubMed

Božič B, Kveder T, Rozman B (2007): Affinity and avidity of autoantibodies In: Shoenfeld Y, Gershwin ME, Meroni PL (eds.). Autoantibodies. Elsevier, Amsterdam: 21-28.

Prince HE, Wilson M (2001): Simplified assay for measuring Toxoplasma gondii immunoglobulin G avidity. Clin Diagn Lab Immunol 8: 904-908. PubMed PMC

Hazell SL. (2007): Clinical utility of avidity assays. Expert Opin Med Diagn 1: 511-519. PubMed

Cucnik S, Bozic B, Kveder T, et al. (2005): Avidity of anti-beta2-glycoprotein I and thrombosis or pregnancy loss in patients with antiphospholipid syndrome. Ann N Y Acad Sci 1051: 141-147. PubMed

Cui Z, Zhao MH (2005): Avidity of anti-glomerular basement membrane autoantibodies was associated with disease severity. Clin Immunol 116: 77-82. PubMed

Suwannalai P, van de Stadt LA, Radner H, et al. (2012): Avidity maturation of anti-citrullinated protein antibodies in rheumatoid arthritis. Arthritis Rheum 64: 1323-1328. PubMed

Fialová L, Malbohan I, Malickova K (2014): Avidity of anticardiolipin antibodies-A factor that could be important for their detection by ELISA methods. J Appl Biomed 12: 277-284.

Fialová L, Petrackova M, Kuchar O (2017): Comparison of different enzyme-linked immunosorbent assay methods for avidity determination of antiphospholipid antibodies. J Clin Lab Anal 31: e22121. PubMed PMC

Fialová L, Bartos A, Svarcova J, et al. (2011): Increased intrathecal high-avidity anti-tau antibodies in patients with multiple sclerosis. PLoS One 6: e27476. PubMed PMC

Fialová L. (2015): Avidity of autoantibodies against antigens in nervous tissue In: Costa A, Villalba E (eds.). Horizons in Neuroscience Research. Nova Science Publishers, New York: 159-169.

Fialová L. (2016): Affinity and avidity of autoantibodies–their clinical significance. Epidemiol Mikrobiol Imunol 65: 155-163. PubMed

Petrovas C, Vlachoyiannopoulos PG, Kordossis T, et al. (1999): Anti-phospholipid antibodies in HIV infection and SLE with or without anti-phospholipid syndrome: comparisons of phospholipid specificity, avidity and reactivity with beta2-GPI. J Autoimmun 13: 347-355. PubMed

Vlachoyiannopoulos PG, Petrovas C, Tektonidou M, et al. (1998): Antibodies to beta 2-glycoprotein-I: urea resistance, binding specificity, and association with thrombosis. J Clin Immunol 18: 380-391. PubMed

Liaskos C, Rigopoulou E, Zachou K, et al. (2005): Prevalence and clinical significance of anticardiolipin antibodies in patients with type 1 autoimmune hepatitis. J Autoimmun 24: 251-260. PubMed

Zachou K, Liaskos C, Rigopoulou E, et al. (2006): Presence of high avidity anticardiolipin antibodies in patients with autoimmune cholestatic liver diseases. Clin Immunol 119: 203-212. PubMed

Bertolaccini ML, Amengual O, Andreoli L, et al. (2014): 14th International Congress on Antiphospholipid Antibodies Task Force. Report on antiphospholipid syndrome laboratory diagnostics and trends. Autoimmun Rev 13: 917-930. PubMed

Carmel-Neiderman NN, Tanne D, Goren I, et al. (2017): Classical and additional antiphospholipid antibodies in blood samples of ischemic stroke patients and healthy controls. Immunol Res 65: 470-476. PubMed

Almanzar G, Ottensmeier B, Liese J, et al. (2013): Assessment of IgG avidity against pertussis toxin and filamentous hemagglutinin via an adapted enzyme-linked immunosorbent assay (ELISA) using ammonium thiocyanate. J Immunol Methods 387: 36-42. PubMed

Lackner KJ, MullerCalleja N (2018): Diagnosis and Management of the Antiphospholipid Syndrome. N Engl J Med 379: 1290. PubMed

Fialová L. (2014): Avidity of antiphospholipid antibodies–our current knowledge. Epidemiol Mikrobiol Imunol 63: 221-225. PubMed

Eisen HN. (2014): Affinity enhancement of antibodies: how low-affinity antibodies produced early in immune responses are followed by high-affinity antibodies later and in memory B-cell responses. Cancer Immunol Res 2: 381-392. PubMed

Dellavance A, Coelho Andrade LE (2014): Immunologic derangement preceding clinical autoimmunity. Lupus 23: 1305-1308. PubMed

Krause S, Landherr U, Agardh CD, et al. (2014): GAD autoantibody affinity in adult patients with latent autoimmune diabetes, the study participants of a GAD65 vaccination trial. Diabetes Care 37: 1675-1680. PubMed

Jianping L, Zhibing Y, Wei Q, et al. (2006): Low avidity and level of serum anti-Abeta antibodies in Alzheimer disease. Alzheimer Dis Assoc Disord 20: 127-132. PubMed

Suwannalai P, Scherer HU, van der Woude D, et al. (2011): Anti-citrullinated protein antibodies have a low avidity compared with antibodies against recall antigens. Ann Rheum Dis 70: 373-379. PubMed

Gelderman KA, Drop AC, Trouw LA, et al. (2014): Serum autoantibodies directed against transglutaminase-2 have a low avidity compared with alloantibodies against gliadin in coeliac disease. Clin Exp Immunol 177: 86-93. PubMed PMC

van Delft MAM, Verheul MK, Burgers LE, et al. (2018): The anti-carbamylated protein antibody response is of overall low avidity despite extensive isotype switching. Rheumatology 57: 1583-1591. PubMed

Mayr A, Schlosser M, Grober N, et al. (2007): GAD autoantibody affinity and epitope specificity identify distinct immunization profiles in children at risk for type 1 diabetes. Diabetes 56: 1527-1533. PubMed

Krause S, Chmiel R, Bonifacio E, et al. (2012): IA-2 autoantibody affinity in children at risk for type 1 diabetes. Clin Immunol 145: 224-229. PubMed

Totland C, Aarseth J, Vedeler C (2007): Hu and Yo antibodies have heterogeneous avidity. J Neuroimmunol 185: 162-167. PubMed

Bozic B, Cucnik S, Kveder T, et al. (2005): Avidity of anti-beta-2-glycoprotein I antibodies. Autoimmun Rev 4: 303-308. PubMed

Cucnik S, Kveder T, Artenjak A, et al. (2012): Avidity of anti-beta2-glycoprotein I antibodies in patients with antiphospholipid syndrome. Lupus 21: 764-765. PubMed

Cucnik S, Kveder T, Ulcova-Gallova Z, et al. (2011): The avidity of anti-beta2-glycoprotein I antibodies in patients with or without antiphospholipid syndrome: a collaborative study in the frame of the European forum on antiphospholipid antibodies. Lupus 20: 1166-1171. PubMed

Steward MW. (1979): Antibody affinity: immunogenetic aspects and relationship to immune complex disease. J Clin Pathol Suppl 13: 120-125. PubMed PMC

Rodriguez-Garcia V, Ioannou Y, Fernandez-Nebro A, et al. (2015): Examining the prevalence of non-criteria anti-phospholipid antibodies in patients with anti-phospholipid syndrome: a systematic review. Rheumatology 54: 2042-2050. PubMed