https://doi.org/10.4081/reumatismo.2024.1701

Cryptogenic stroke and seronegative antiphospholipid syndrome: a case series of patients with positivity for “non-criteria” antiphospholipid antibodies

Vol. 76 No. 4 (2024)
Submitted: 25 January 2024
Accepted: 23 May 2024
Published: 25 September 2024
Cryptogenic IS, SN-APS, aCL/Vim, TLC-immunostaining
Abstract Views: 538
PDF: 14
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Authors

S. Mancuso
Rheumatology Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, “Sapienza” University of Rome, Italy.
M. De Michele
https://orcid.org/0000-0002-3928-4309
Stroke Unit, Emergency Department, “Sapienza” University of Rome, Italy.
S. Truglia
simona.truglia@uniroma1.it
Rheumatology Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, “Sapienza” University of Rome, Italy.
A. Capozzi
https://orcid.org/0000-0001-6508-7731
Department of Experimental Medicine, “Sapienza” University of Rome, Italy.
L. Rapino
https://orcid.org/0009-0007-5163-9807
Rheumatology Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, “Sapienza” University of Rome, Italy.
I. Berto
Stroke Unit, Emergency Department, “Sapienza” University of Rome, Italy.
C. Alessandri
https://orcid.org/0000-0003-4149-5321
Rheumatology Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, “Sapienza” University of Rome, Italy.
D. Toni
Stroke Unit, Emergency Department, “Sapienza” University of Rome, Italy.
V. Manganelli
Department of Experimental Medicine, “Sapienza” University of Rome, Italy.
M. Sorice
Department of Experimental Medicine, “Sapienza” University of Rome, Italy.
F. Conti
Rheumatology Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, “Sapienza” University of Rome, Italy.

Cerebrovascular events (CE) are one of the most common and severe events in antiphospholipid syndrome (APS), a condition characterized by thrombosis and circulating anti-phospholipid antibodies (aPL). Seronegative APS (SN-APS) refers to a group of patients with clinical features of APS but persistently negative tests for “criteria aPL”: anti-cardiolipin antibodies (aCL) and anti-β2glycoprotein I antibodies detected by enzyme-linked immunosorbent assay (ELISA), and the lupus anticoagulant detected by clotting assays. We report a series of five cases of SN-APS in young or middle-aged patients who tested positive for “non-criteria” aPL. We retrospectively collected cases of SN-APS patients who experienced CE without an identified cause despite an extensive diagnostic work-up and tested negative for criteria aPL. All the patient sera were tested for aCL by immunostaining on thin-layer chromatography (TLC) and anti-vimentin/cardiolipin (aCL/Vim) by ELISA. We identified five cases of female patients aged 21 to 58 years, evaluated at the Rheumatology Unit and/ or Stroke Unit/Emergency Department of the Sapienza University Hospital of Rome, “Policlinico Umberto I”. All patients presented a clinical history suggestive of APS. All the patients tested positive for aCL by TLC-immunostaining, and one patient was positive for aCL/Vim. In young or middle-aged patients with cryptogenic CE and a clinical history suggestive of APS, the use of new diagnostic tools for identifying aPL, if validated in future studies, could represent an important step in the prompt diagnosis of APS.

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Citations

Crossref
Scopus
Google Scholar
Europe PMC
Hughes GRV. The anticardiolipin syndrome. Clin Exp Rheumatol 1985; 3: 285-6
Andreoli L, Chighizola CB, Banzato A, Pons-Estel GJ, Ramire de Jesus G, Erkan D. Estimated frequency of antiphospholipid antibodies in patients with pregnancy morbidity, stroke, myocardial infarction, and deep vein thrombosis: a critical review of the literature. Arthritis Care Res 2013; 65: 1869-73.
Hughes GRV, Khamashta MA. Seronegative antiphospholipid syndrome. Ann Rheum Dis 2003; 62: 1127.
Barbhaiya M, Zuily S, Naden R, Hendry A, Manneville F, Amigo AC, et al. 2023 ACR/EULAR antiphospholipid syndrome classification criteria. Ann Rheum Dis 2023; 82: 1258-70.
Conti F, Andreoli L, Crisafulli F, Mancuso S, Truglia S, Tektonidou MG. Does seronegative obstetric APS exist?“pro” and “cons”. Autoimmun Rev 2019; 18: 102407.
Truglia S, Mancuso S, Capozzi A, Recalchi S, Riitano G, Longo A, et al. ‘Non-criteria antiphospholipid antibodies’: bridging the gap between seropositive and seronegative antiphospholipid syndrome. Rheumatology 2022; 61: 826-33.
Conti F, Alessandri C, Spinelli FR, Capozzi A, Martinelli F, Recalchi S, et al. TLC immunostaining for detection of ‘antiphospholipid’ antibodies. Methods Mol Biol 2014; 1134: 95-101.
Osteraas ND, Dafer RM. Advances in management of the stroke etiology one-percenters. Curr Neurol Neurosci Rep 2023; 23: 301-25.
Ricarte IF, Dutra LA, Abrantes FF, Toso FF, Barsottini OGP, Silva GS, et al. Neurologic manifestations of antiphospholipid syndrome. Lupus 2018; 27: 1404-14.
Tanaka Y, Ueno Y, Miyamoto N, Shimada Y, Tanaka R, Hattori N, et al. Patent foramen ovale and atrial septal aneurysm can cause ischemic stroke in patients with antiphospholipid syndrome. J Neurol 2013; 260: 189-96.
Cervera R, Piette JC, 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.
Truglia S, Capozzi A, Mancuso S, Recalchi S, Spinelli FR, Perricone C, et al. A monocentric cohort of obstetric seronegative anti-phospholipid syndrome. Front Immunol 2018; 9: 1678.
Zohoury N, Bertolaccini ML, Rodriguez-Garcia JL, Shums Z, Ateka-Barrutia O, Sorice M, et al. Closing the serological gap in the antiphospholipid syndrome: the value of “non-criteria” antiphospholipid antibodies. J Rheumatol 2017; 44: 1597-602.
Capozzi A, Riitano G, Mancuso S, Recalchi S, Manganelli V, Garofalo T, et al. Anti-vimentin/cardiolipin IgA in the anti-phospholipid syndrome: a new tool for 'seronegative' diagnosis. Clin Exp Immuno 2021; 205: 326-32.
Tektonidou MG, Andreoli L, Limper M, Amoura Z, Cervera R, Costedoat-Chalumeau N, et al. EULAR recommendations for the management of antiphospholipid syndrome in adults. Ann Rheum Dis 2019; 78: 1296-304.

How to Cite

Mancuso, S., De Michele, M., Truglia, S., Capozzi, A., Rapino, L., Berto, I., … Conti, F. (2024). Cryptogenic stroke and seronegative antiphospholipid syndrome: a case series of patients with positivity for “non-criteria” antiphospholipid antibodies. Reumatismo, 76(4). https://doi.org/10.4081/reumatismo.2024.1701
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