Abstract
Although numerous studies investigated the association between homocysteine (Hcy), tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP) and apolipoproteins (apos) with thrombosis and/or recurrent pregnancy losses, studies that analyzed the abovementioned parameters and multiple positivity of antiphospholipid antibodies (aPL Abs) in patients with primary antiphospholipid syndrome (PAPS) are lacking. Therefore, the aim of this study was to analyze the presence of various combinations of the abovementioned parameters and their associations with clinical and/or serological features of PAPS. High-pressure liquid chromatography (HPLC) was used for determination of Hcy, while apoAI, apoB, and lipoprotein (Lp) (a) concentrations were estimated by immunonephelometry. High-sensitivity C-reactive protein (hsCRP) was measured by immunoturbidimetry. Apo (a), TNF-α, and aPL Abs were measured by ELISA. Various combinations of analyzed parameters (Hcy/CRP/TNF/apoAI/apoB/apo (a)/Lp (a)) were not associated with a single presence of either aPL Abs. Double positivity for both isotypes of anticardiolipin (aCL) Abs (IgG + IgM) was associated with the increased apoB levels. The presence of the IgG isotype of both aCL + anti-beta2 glycoprotein I (aβ2gpI) Abs was associated with the highest number of analyzed parameters (i.e., increased levels of hsCRP, Lp (a), and apo (a)). The presence of the IgG isotype of both aCL + aβ2gpI Abs was associated with the highest number of vascular impairment parameters in patients with PAPS, and this combination confers the highest risk for the recurrence of thrombotic episodes. This is the first report that analyzed the association between various combinations of vascular impairment parameters with multiple aPL Ab positivity. Our results provide a rationale for further investigations of therapeutic approaches for PAPS patients.
Similar content being viewed by others
References
Bertolaccini ML, Ammengual O, Andreolii 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
Miyakis S, Lockshin MD, Atsumi T et al (2006) International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome. J Thromb Haemost 4:295–306
van den Hoogen LL, van Roon JAG, Radstake TRDJ et al (2015) Delineating the deranged immune system in the antiphospholipid syndrome. Autoimmun Rev. doi:10.1016/j.autrev.2015.08.011
D’Ippolito S, Meroni PL, Koike T, Veglia M, Scambia G, Di Simone N (2014) Obstetric antiphospholipid syndrome: a recent classification for an old defined disorder. Autoimmun Rev 13:901–908
Doring Y, Hurst J, Lorenz M et al (2010) Human antiphospholipid antibodies induce TNFa in monocytes via Toll-like receptor 8. Immunobiology 215:230–241
Nandeesha H, Bobby Z, Selvaraj N et al (2015) Pre-hypertension: is it an inflammatory state? Clin Chim 451:338–342
Popa C, Netea MG, van Riel PLCM et al (2007) The role of TNF-alpha in chronic inflammatory conditions, intermediary metabolism, and cardiovascular risk. J Lipid Res 48:751–762
Ozturk ZG, Ekmekci H, Ekmecki OB et al (2010) Nontraditional risk factors in carotid artery disease. Clin Appl Thromb/Hemost 16(5):554–558
Himerova J (2013) Homocysteine and venous thromboembolism—is there any link? Cor Et Vasa 55:E248–E258
Lee RM, Brown MA, Ward K, Nelson L, Branch DW, Silver RM (2004) Homocysteine levels in women with antiphospholipid syndrome and normal fertile controls. J Rep Immunol 63:23–30
Baraka E, El Dein M, Farouk H, Moutaz YE (2015) Hyperhomocysteinemia and metabolic syndrome are risk factors for sub-clinical atherosclerosis in women with systemic lupus erythematosus. Egypt Rheumatol 37:67–74
Papageorgiou N, Tousoulis D (2015) Interaction between HDL and inflammation: when the good turns to be bad. Int J Cardiol 189:15–17
Bećarević M, Andrejević S, Miljić P, Bonači-Nikolić B, Majkić-Singh N (2007) Serum lipids and anti-oxidized LDL antibodies in primary antiphospholipid syndrome. Clin Exp Rheumatol 25(3):361–366
Bećarević M, Ignjatović S (2016) Proinflammatory proteins in female and male patients with primary antiphospholipid syndrome: preliminary data. Clin Rheumatol. doi:10.1007/s10067-016-3345-3
Brandt JT, Triplett DA, Alving B et al (1995) Criteria for the diagnosis of lupus anticoagulants: an update on behalf of the Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society of Thrombosis and Haemostasis. Thromb Haemost 74(4):1185–1190
Just SA, Nybo M, Laustrup H, Jensen Hansen IM, Junker P, Just Vinholt P (2016) Single test isolated lupus anticoagulant positivity is associated with increased plasma levels of inflammatory markers and dyslipidemia. Lupus 25:241–247
Saraiva SS, Custodio IF, de Moraes Mazzeto B et al (2015) Recurrent thrombosis in antiphospholipid syndrome may be associated with cardiovascular risk factors and inflammatory response. Thromb Res 136:1174–1178
Kronenberg F (2014) Lipoprotein (a) in various conditions: to keep a sense of proportions. Atherosclerosis 234:249–251
Cugno M, Borghi MO, Lonati LM et al (2010) Patients with antiphospholipid syndrome display endothelial perturbation. J Autoimmun 34:105–110
Olszanecka-Glinianowicz M, Chudek J, Kocelak P et al (2011) Body fat changes and activity of tumor necrosis factor a system-a 5-year follow-up study. Metab Clin Exp 60:531–536
Peluso I, Palmery M (2015) The relationship between body weight and inflammation: lesson from anti-TNFa antibody therapy. Human Immunol. doi:10.1016/j.humimm.2015.10.008
Caldas CA, da Mota LMH, de Carvalho JF (2011) Obesity in primary antiphospholipid syndrome is associated with worse outcome. Joint Bone Spine 78:319–325
Miesbach W, Gokpinar B, Gilzinger A, Claus D, Scharrer I (2005) Predictive role of hs-C-reactive protein in patients with antiphospholipid syndrome. Immunobiology 210:755–760
Batuca JR, Ames PR, Amaral M et al (2009) Anti-atherogenic and anti-inflammatory properties of high-density lipoprotein are affected by specific antibodies in systemic lupus erythematosus. Rheumatology (Oxford) 48(1):26–31
Svenungsson E, Fei GZ, Jensen-Urstad K et al (2003) TNF-alpha: a link between hypertriglyceridaemia and inflammation in SLE patients with cardiovascular disease. Lupus 12:454–461
Acknowledgments
We would like to thank all the patients who participated in this study and our colleagues from numerous clinics.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
All procedures performed in our study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Funding
The present work was supported by the Ministry of Science and Education of the Republic of Serbia on the basis of contract no. 175036. None of the authors had the conflicting financial interest.
Disclosures
None.
The authors alone are responsible for the content and writing of the paper.
Rights and permissions
About this article
Cite this article
Bećarević, M., Mirković, D. & Ignjatović, S. Double positivity of the IgG isotype of both anticardiolipin and anti-β2gpI antibodies is associated with the highest number of vascular impairment parameters in patients with primary antiphospholipid syndrome: preliminary data. Clin Rheumatol 35, 2947–2954 (2016). https://doi.org/10.1007/s10067-016-3438-z
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10067-016-3438-z