Volume 144, April 2024, 103173Author links open overlay panel, , , , , , , AbstractBackground

Antiphospholipid syndrome (APS) is a rare autoimmune disease characterized by thromboses at various sites and obstetric events associated with the persistent presence of antiphospholipid antibodies. The identification of clinical phenotypes in APS patients is a clinical need. In this study, we aimed to determine the clinical phenotypes of APS patients through an unsupervised analysis of two well-characterized cohorts of APS patients.

Patients and methods

APS phenotypes were defined by an ascending hierarchical cluster analysis to identify preferential associations between 18 types of organ involvement and clinical characteristics. This analysis was performed on an initial multi-center cohort of 1000 patients, with validation in a replication cohort of 435 patients.

Results

The hierarchical analysis identified three APS phenotypes in both the initial and replication cohorts: an obstetric phenotype (n = 259 and n = 74 patients, respectively), a venous thrombosis phenotype, accounting for the largest number of patients (n = 461 and n = 297 patients, respectively), and a skin-central nervous system-heart phenotype (n = 280 and n = 64 patients, respectively). The clinical characteristics of the patients differed significantly between the three phenotypes, but there was no difference in antiphospholipid antibody profile between the groups.

Conclusions

We identified three phenotypes of APS defined based on preferential associations of organ involvements and differences in presentation. These observations may help clinicians to detect organ involvement and to manage treatment.

Section snippetsStudy design

We used the European cohort of 1000 patients from the Europhospholipid project described in 2002 [3] as the initial cohort. The patient selection and clinical features of this cohort have been already described in details. In brief, this cohort was constituted for prospective, multicenter, consecutive-patient study between 1990 and 1999, at 20 tertiary referral centres in Europe.

We used a single-centre APS cohort from a tertiary reference centre in France as the replication cohort. Patients

Clinical characteristics and phenotypes of the initial cohort

The initial cohort included 1000 patients, predominantly women (n = 820, 82 % women), with a mean age at APS onset of 34 (±13) years. Main characteristics of this cohort have been described elsewhere [3] and are summarized in Table 2. The main clinical manifestations were: deep vein thrombosis of a lower limb or pulmonary embolism (43 %), fetal loss or late pregnancy loss (>10 weeks of gestation (WG)) (32 %), thrombocytopenia (30 %), stroke/transient ischemic attack (28 %), livedo (24 %),

Biology

The biological parameters of the patients in the whole cohort and in the various clusters are shown in Table 2, Table 3 In the initial cohort, the prevalence of positivity for lupus anticoagulant was 56 %, the prevalence of anti-beta2GP1 antibodies (IgG or IgM) was 41 %, and the prevalence of anticardiolipin antibodies (IgG or IgM) was 88 %. Similar results were obtained for the replication cohort, in which the prevalence of lupus anticoagulant was 60 %, the prevalence of anti-beta2GP1

Discussion

In this study, we identified three APS phenotypes in a large European multicenter cohort of 1000 well-characterized patients. These phenotypes were confirmed in a replication cohort of 435 patients diagnosed between 2013 and 2020 based on more recent classification criteria [2]. These phenotypes can be summarized as follows [1]: an obstetric phenotype in young women, associated with a lower risk of non-obstetric manifestations other than venous thromboembolism [2]; a venous thrombosis

Conclusion

Through an analysis of two independent databases of APS patients, we identified three APS phenotypes: an obstetric phenotype in young women experiencing obstetric events and venous thrombosis; a venous thrombosis phenotype, accounting for the largest proportion of patients in this study; and a skin–CNS–heart phenotype, with a high prevalence of strokes, livedo, valvulopathy, nephropathy and thrombocytopenia. This study reveals the existence of preferential associations between organ

Authors’ contributions

R.C., Z.A. and F.C.A. designed the study, D.T., Q.M., R.C., R.L., F.C.-A obtained the data, D.T., Q.M., R.L., I.A.-M. and F.C.-A. Formal analysis, D.T., Q.M., R.L., I.A.-M., Z.A. and F.C.-A. analyzed and interpreted the data, D.T. and F.C.-A. wrote the manuscript, All authors critically reviewed and approved the final version of the manuscript Structured

Data sharing statement

Data will be shared upon reasonable request to the corresponding author.

Conflicts of interest

The authors declare that they have no conflicts of interest to report. D.T. was supported by La Fondation du Souffle (Formation pour la Recherche 2020 grant). This work received no additional financial support.

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