Session Type: Poster Session (Sunday)
Session Time: 9:00AM-11:00AM
Background/Purpose: The clinical significance of non-canonical anti-phosphatidylserine/prothrombin (aPS/PT) antibodies in antiphospholipid syndrome (APS) is still controversial. This study assessed the prevalence of aPS/PT antibodies, their association with different APS clinical phenotypes and their involvement in the serum and monocytes molecular profiles.
Methods: Forty APS patients and 40 healthy donors were examined. Anti-cardiolipin (aCL), anti-β2GP-I and aPS/PT antibodies (IgG, IgM and IgA isotypes), as well as lupus anticoagulant (LA) were tested. In parallel, monocytes from peripheral blood were purified by positive immunomagnetic selection. Gene expression microarray (Agilent GF112F) and nCounter microRNA expression array (Nanostring) were performed. Separately, a miRNA array in the plasma of those patients was performed, along with the analysis of their inflammatory profile by multiplex assay. Selected genes and miRNAs found significantly altered and related to the prothrombotic and obstetric pathology in APS were validated in the whole cohort by qPCR. The involvement of the presence and titers of canonical and non-canonical autoantibodies on the altered inflammatory and gene/miRNA profiles were assessed by multiple comparison tests.
Results: aPS/PT antibodies were detected in 11 out of 26 APS patients (42,3%): 6 carriers of the IgM isotype, 1 carrier of IgA isotype, 1 carrier of both IgM and IgA isotypes and 3 carriers of the three isotypes (IgG/IgA/IgM) simultaneously. The 3 isotypes of aPS/PT antibodies were significantly associated with isolated LA positivity. Among them, there was a prevalence of IgM aPS/PT antibodies in thrombotic patients, and of IgA aPS/PT antibodies in patients with obstetric complications. Levels of IgM aPS/PT were significantly different in APS patients with thrombotic manifestations and those with fetal loss.
Inflammatory profile in plasma of APS patients positive for these non-canonical antibodies showed significantly increased levels of a number of pro-inflammatory mediators (IL2, IL4, IL6, INFg, IL8, IL10, IL12, IL17, GM-CSF, MIP1a, MIP1b) in relation to patients positive for canonical antibodies, along with reduced levels of serum miR26a-5p.
Accordingly, monocytes from APS patients positive for aPS/PT displayed slightly distinctive gene/miRNA profiles related to atherosclerosis and thrombosis than those negative for non-canonical antibodies compared with HDs. Moreover, increased IFNg mRNA classified patients positive or negative for aPS/PT antibodies. This IFNg altered expression might be related to the occurrence of obstetrical complications, as observed by its increased expression in aPS/PT positive obstetric patients in relation to thrombotic patients.
Conclusion: Conclusions: Anti-PS/PT antibodies are frequent in primary APS patients positive for other antiphospholipid antibodies, are associated with different clinical features, and confer distinctive molecular profiles. Thus, anti-PS/PT antibodies might constitute a useful serological tool in the diagnosis, phenotypic and molecular characterization of APS patients.
Funded by ISCIII, PI18/00837 and RIER RD16/0012/0015 co-funded with FEDER
To cite this abstract in AMA style:Lopez-Pedrera C, Aguirre-Zamorano M, Pérez-Sanchez L, Patiño-Trives A, Luque-Tevar M, Ibañez-Costa A, Arias de la Rosa I, Abalos-Aguilera M, Alacaide-Ruggiero L, Ortega R, Barbarroja N, Collantes-Estevez E, Radin M, Cecchi I, Sciascia S, Perez-Sanchez C. Anti-phosphatidylserine/prothrombin Antibodies Confer a Distinctive Molecular Profile in Primary Antiphospholipid Syndrome Patients [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/anti-phosphatidylserine-prothrombin-antibodies-confer-a-distinctive-molecular-profile-in-primary-antiphospholipid-syndrome-patients/. Accessed January 27, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-phosphatidylserine-prothrombin-antibodies-confer-a-distinctive-molecular-profile-in-primary-antiphospholipid-syndrome-patients/