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Current Rheumatology Reports
Published in: Current Rheumatology Reports 10/2018

01-10-2018 | Antiphospholipid Syndrome (S Zuily, Section Editor)

Role of Infectious Diseases in the Antiphospholipid Syndrome (Including Its Catastrophic Variant)

Authors: Claudia Mendoza-Pinto, Mario García-Carrasco, Ricard Cervera

Published in: Current Rheumatology Reports | Issue 10/2018

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Abstract

Purpose of Review

The antiphospholipid syndrome (APS) is characterized by the development of thrombotic events and pregnancy morbidity in the presence of antiphospholipid antibodies (aPL). An infectious etiology for this syndrome has been postulated. The present review is aimed to summarize recent evidence about the role of infections and vaccines in the pathogenesis of the APS (including its catastrophic variant).

Recent Findings

There is an increased risk of developing aPL in various infections, particularly in viral infections. The most frequent infection related to aPL has been hepatitis C virus. These antibodies may be associated with thromboembolic events, including catastrophic APS. There is a link between vaccinations, such as the tetanus toxoid and aPL, due to molecular mimicry between the two molecules.

Summary

Accumulated evidence supports that the presence of aPL is associated with a variety of infections, including viruses, bacteria, fungi, and parasites, and the main mechanism to explain this correlation is molecular mimicry. Moreover, a link between vaccinations, such as the tetanus toxoid, and APS has also been described.
Literature
1.
Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4:295–306.CrossRefPubMed
2.
3.
4.
Koike T, Sueishi M, Funaki H, Tomioka H, Yoshida S. Anti-phospholipid antibodies and biological false positive serological test for syphilis in patients with systemic lupus erythematosus. Clin Exp Immunol. 1984;56:193–9.PubMedPubMedCentral
5.
Cervera R, Piette J-C, Font J, Khamashta MA, Shoenfeld Y, Camps MT, et al. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum. 2002;46:1019–27.CrossRefPubMed
6.
Juby AG, Davis P. Prevalence and disease associations of certain autoantibodies in elderly patients. Clin Invest Med. 1998;21:4–11.PubMed
7.
Shi W, Krilis SA, Chong BH, Gordon S, Chesterman CN. Prevalence of lupus anticoagulant and anticardiolipin antibodies in a healthy population. Aust NZ J Med. 1990;20:231–6.CrossRef
8.
Asherson RA, Cervera R. “Primary”, “secondary” and other variants of the antiphospholipid syndrome. Lupus. 1994;3:293–8.CrossRefPubMed
9.
Shoenfeld Y, Blank M, Cervera R, Font J, Raschi E, Meroni P-L. Infectious origin of the antiphospholipid syndrome. Ann Rheum Dis. 2006. p. 2–6.
10.
Cacoub P, Musset L, Amoura Z, Guilani P, Chabre H, Lunel F, et al. Anticardiolipin, anti-beta2-glycoprotein I, and antinucleosome antibodies in hepatitis C virus infection and mixed cryoglobulinemia. Multivirc Group J Rheumatol. 1997;24:2139–44.PubMed
11.
• Huh JY, Yi DY, Hwang SG, Choi JJ, Kang MS. Characterization of antiphospholipid antibodies in chronic hepatitis B infection. Korean J Hematol. 2011, 46:36–40. Article that describes a novel technique that differentiates between antiphospholipid syndrome and asymptomatic antiphospholipid antibody carriers or patients with infectious diseases.CrossRefPubMedPubMedCentral
12.
Abdel-Wahab N, Talathi S, Lopez-Olivo MA, Suarez-Almazor ME. Risk of developing antiphospholipid antibodies following viral infection: a systematic review and meta-analysis. Lupus. 2018;27:572–83.CrossRefPubMed
13.
Castanon A, Pierre G, Willis R, Harris EN, Papalardo E, Romay-Penabad Z, et al. Performance evaluation and clinical associations of immunoassays that detect antibodies to negatively charged phospholipids other than Cardiolipin. Am J Clin Pathol. 2018;29:401–11.CrossRef
14.
Roggenbuck D, Borghi MO, Somma V, Buttner T, Schierack P, Hanack K, et al. Antiphospholipid antibodies detected by line immunoassay differentiate among patients with antiphospholipid syndrome, with infections and asymptomatic carriers. Arthritis Res Ther. 2016;18:111.CrossRefPubMedPubMedCentral
15.
• Palomo I, Alarcon M, Sepulveda C, Pereira J, Espinola R, Pierangeli S. Prevalence of antiphospholipid and antiplatelet antibodies in human immunodeficiency virus (HIV)-infected Chilean patients. J Clin Lab Anal. 2003;17:209–15. A systematic review and meta-analysis of articles linking viral hepatitis and antiphospholipid antibodies.CrossRefPubMedPubMedCentral
16.
• Brew BJ, Miller J. Human immunodeficiency virus type 1-related transient neurological deficits. Am J Med. 1996, 101:257–61. A systematic review of articles linking viral infection and antiphospholipid antibodies.CrossRefPubMed
17.
Dalekos GN, Kistis KG, Boumba DS, Voulgari P, Zervou EK, Drosos AA, et al. Increased incidence of anti-cardiolipin antibodies in patients with hepatitis C is not associated with aetiopathogenetic link to anti-phospholipid syndrome. Eur J Gastroenterol Hepatol. 2000;12:67–74.CrossRefPubMed
18.
Zachou K, Liaskos C, Christodoulou DK, Kardasi M, Papadamou G, Gatselis N, et al. Anti-cardiolipin antibodies in patients with chronic viral hepatitis are independent of beta2-glycoprotein I cofactor or features of antiphospholipid syndrome. Eur J Clin Investig. 2003;33:161–8.CrossRef
19.
Sene D, Piette J-C, Cacoub P. Antiphospholipid antibodies, antiphospholipid syndrome and infections. Autoimmun Rev. 2008;7:272–7.CrossRefPubMed
20.
Ambrosino P, Lupoli R, Tarantino P, Di Minno A, Tarantino L, Di Minno MND. Viral hepatitis and anti-phospholipid antibodies positivity: a systematic review and meta-analysis. Dig Liver Dis. 2015;47:478–87.CrossRefPubMed
21.
Alessandri C, Bombardieri M, Di Prospero L, Conigliaro P, Conti F, Labbadia G, et al. Anti-lysobisphosphatidic acid antibodies in patients with antiphospholipid syndrome and systemic lupus erythematosus. Clin Exp Immunol. 2005;140:173–80.CrossRefPubMedPubMedCentral
22.
Abdel-Wahab N, Lopez-Olivo MA, Pinto-Patarroyo GP, Suarez-Almazor ME. Systematic review of case reports of antiphospholipid syndrome following infection. Lupus. 2016;25:1520–31.CrossRefPubMedPubMedCentral
23.
Cole FS, Brusch JL, Talarico L. A circulating anticoagulant in lepromatous leprosy. Int J Lepr Other Mycobact Dis. 1979;47:121–5.PubMed
24.
de Larranaga GF, Forastiero RR, Martinuzzo ME, Carreras LO, Tsariktsian G, Sturno MM, et al. High prevalence of antiphospholipid antibodies in leprosy: evaluation of antigen reactivity. Lupus. 2000;9:594–600.CrossRefPubMed
25.
Ilarraza H, Marquez MF, Alcocer A, Banales JL, Nava AH, Reyes PA. Anticardiolipin antibodies are not associated with rheumatic heart disease. Lupus. 2001;10:873–5.CrossRefPubMed
26.
Ordi-Ros J, Selva-O’Callaghan A, Monegal-Ferran F, Monasterio-Aspiri Y, Juste-Sanchez C, Vilardell-Tarres M. Prevalence, significance, and specificity of antibodies to phospholipids in Q fever. Clin Infect Dis. 1994;18:213–8.CrossRefPubMed
27.
Million M, Bardin N, Bessis S, Nouiakh N, Douliery C, Edouard S, et al. Thrombosis and antiphospholipid antibody syndrome during acute Q fever: a cross-sectional study. Medicine (Baltimore). 2017;96:e7578.CrossRef
28.
•• Ascer E, Marques M, Gidlund M. M pneumoniae infection, pulmonary thromboembolism and antiphospholipid antibodies. BMJ Case Rep. 2011;pii: bcr1220103561. A systematic review of articles linking viral infections and antiphospholipid antibodies.
29.
Greco TPJ, Conti-Kelly AM, Greco TP. Antiphospholipid antibodies in patients with purported “chronic Lyme disease”. Lupus. 2011;20:1372–7.CrossRefPubMed
30.
Stasi R, Stipa E, Masi M, Oliva F, Sciarra A, Perrotti A, et al. Prevalence and clinical significance of elevated antiphospholipid antibodies in patients with idiopathic thrombocytopenic purpura. Blood. 1994;84:4203–8.PubMed
31.
Cotticelli L, Borrelli M, D’Alessio AC, Menzione M, Villani A, Piccolo G, et al. Central serous chorioretinopathy and Helicobacter pylori. Eur J Ophthalmol. 2006;16:274–8.CrossRefPubMed
32.
Medina G, Briones-Garcia E, Cruz-Dominguez MP, Florez-Durante OI, Jara LJ. Antiphospholipid antibodies disappearance in primary antiphospholipid syndrome: thrombosis recurrence. Autoimmun Rev. 2017;16:352–4.CrossRefPubMed
33.
Blank M, Krause I, Magrini L, Spina G, Kalil J, Jacobsen S, et al. Overlapping humoral autoimmunity links rheumatic fever and the antiphospholipid syndrome. Rheumatology (Oxford). 2006;45:833–41.CrossRef
34.
da Silva F, de Carvalho J. Rheumatic fever associated with antiphospholipid syndrome: systematic review. J Immunol Res. 2014;2014:614591.PubMedPubMedCentral
35.
Figueroa F, Berrios X, Gutierrez M, Carrion F, Goycolea JP, Riedel I, et al. Anticardiolipin antibodies in acute rheumatic fever. J Rheumatol. 1992;19:1175–80.PubMed
36.
de Carvalho JF, Goldenstein-Schainberg C. Lack of antiphospolipid antibodies in long-term cardiac rheumatic fever. Rheumatol. Int. 2012. p. 2951.
37.
Skouri H, Gandouz R, Kraiem I, Harrabi I, Ben SM. Antibodies to anionic phospholipids and cofactors in kala-azar. Comparative study with malaria, toxoplasmosis and “autoimmune diseases”. Clin Exp Rheumatol. 2008;26:894–902.PubMed
38.
Tavakoli M, Roghaee S, Soheilian R, Soheilian M. Antiphospholipid syndrome following toxoplasma retinochoroiditis. Ocul Immunol Inflamm. 2011;19:311–3.CrossRefPubMed
39.
Santiago M, Martinelli R, Ko A, Reis EA, Fontes RD, Nascimento EG, et al. Anti-beta2 glycoprotein I and anticardiolipin antibodies in leptospirosis, syphilis and kala-azar. Clin Exp Rheumatol. 2001;19:425–30.PubMed
40.
•• Cervera R, Font J, Gomez-Puerta JA, Espinosa G, Cucho M, Bucciarelli S, et al. Validation of the preliminary criteria for the classification of catastrophic antiphospholipid syndrome. Ann Rheum Dis. 2005;64:1205–9. A comprehensive review of the link between infectious diseases and the catastrophic antiphospholipid syndrome.CrossRefPubMedPubMedCentral
41.
Cervera R, Rodriguez-Pinto I, Colafrancesco S, Conti F, Valesini G, Rosario C, et al. 14th International Congress on Antiphospholipid Antibodies Task Force Report on Catastrophic Antiphospholipid Syndrome. Autoimmun Rev. 2014. p. 699–707.CrossRefPubMed
42.
Rodriguez-Pinto I, Moitinho M, Santacreu I, Shoenfeld Y, Erkan D, Espinosa G, et al. Catastrophic antiphospholipid syndrome (CAPS): descriptive analysis of 500 patients from the International CAPS Registry. Autoimmun Rev. 2016;15:1120–4.CrossRefPubMed
43.
Betancur J-F, Navarro E-P, Echeverry A, Moncada PA, Canas CA, Tobon GJ. Hyperferritinemic syndrome: Still’s disease and catastrophic antiphospholipid syndrome triggered by fulminant Chikungunya infection: a case report of two patients. Clin Rheumatol. 2015;34:1989–92.CrossRefPubMed
44.
Betancur J-F, Navarro EP, Bravo Bonilla JH, Cortes AD, Velez JD, Echeverry A, et al. Catastrophic antiphospholipid syndrome triggered by fulminant chikungunya infection in a patient with systemic lupus erythematosus. Arthritis Rheumatol (Hoboken, NJ). 2016;68:1044.CrossRef
45.
Espinosa G, Cervera R, Asherson RA. Catastrophic antiphospholipid syndrome and sepsis. A common link? J Rheumatol. 2007. p. 923–6.
46.
Bucciarelli S, Espinosa G, Cervera R. The CAPS Registry: morbidity and mortality of the catastrophic antiphospholipid syndrome. Lupus. 2009;18:905–12.CrossRefPubMed
47.
Inic-Kanada A, Stojanovic M, Zivkovic I, Kosec D, Micic M, Petrusic V, et al. Murine monoclonal antibody 26 raised against tetanus toxoid cross-reacts with beta2-glycoprotein I: its characteristics and role in molecular mimicry. Am J Reprod Immunol. 2009;61:39–51.CrossRefPubMed
48.
Zivkovic I, Stojanovic M, Petrusic V, Inic-Kanada A, Dimitrijevic L. Induction of APS after TTd hyper-immunization has a different outcome in BALB/c and C57BL/6 mice. Am J Reprod Immunol. 2011;65:492–502.CrossRefPubMed
49.
Bizjak M, Bruck O, Kanduc D, Praprotnik S, Shoenfeld Y. Vaccinations and secondary immune thrombocytopenia with antiphospholipid antibodies by human papillomavirus vaccine. Semin Hematol. 2016;53(Suppl 1):S48–50.CrossRefPubMed
50.
de Medeiros DM, Silva CA, Bueno C, Ribeiro ACM. Viana V dos ST, Carvalho JF, et al. Pandemic influenza immunization in primary antiphospholipid syndrome (PAPS): a trigger to thrombosis and autoantibody production? Lupus. 2014;23:1412–6.CrossRefPubMed
51.
Vista ES, Crowe SR, Thompson LF, Air GM, Robertson JM, Guthridge JM, et al. Influenza vaccination can induce new-onset anticardiolipins but not beta2-glycoprotein-I antibodies among patients with systemic lupus erythematosus. Lupus. 2012;21:168–74.CrossRefPubMedPubMedCentral
Metadata
Title
Role of Infectious Diseases in the Antiphospholipid Syndrome (Including Its Catastrophic Variant)
Authors
Claudia Mendoza-Pinto
Mario García-Carrasco
Ricard Cervera
Publication date
01-10-2018
Publisher
Springer US
Published in
Current Rheumatology Reports / Issue 10/2018
Print ISSN: 1523-3774
Electronic ISSN: 1534-6307
DOI
https://doi.org/10.1007/s11926-018-0773-x

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