Antiphospholipid Syndrome: Clinical Characteristics of Patients and Affected Family Members From Multiplex Families.

Antiphospholipid syndrome (APS) is characterized by venous and/or arterial thromboembolic events, recurrent fetal loss, and persistently elevated antiphospholipid antibody (aPL) levels. Familial clustering of individuals with elevated aPL levels occurs, and up to 37% of patients with APS have one or more relatives with at least one clinical feature of APS. Individuals with elevated aPL levels or APS are also frequently identified in families with other autoimmune (AI) disorders, such as lupus or rheumatoid arthritis. Individuals with different autoimmune disorders appear to share common susceptibility loci, suggesting that a common set of susceptibility genes may contribute to clinically distinct autoimmune disorders. To investigate the heritability of APS, we are enrolling patients with APS who have one or more family members affected by APS (multiplex APS) or by other, non-APS, autoimmune disorders (multiplex AI). This study summarizes clinical characteristics of probands and family members enrolled to date in these two groups.

Probands meeting clinical and laboratory criteria for APS (Miyakis, et al. J.Thromb.Haemost, 2006;4: 295-306) who had at least one clinically affected relative positive for either APS or another autoimmune disorder (e.g., lupus, rheumatoid arthritis) were recruited and enrolled into the study. A detailed personal and family history was obtained and relevant family members were also approached to participate in the study. Blood specimens were collected for genetic, serologic, and coagulation testing.

Review of more than 200 potential participants identified 13 probands with multiplex APS families and 49 with multiplex AI families. Probands from both groups more frequently had primary rather than secondary APS, and thromboembolic events were the most common clinical manifestation. Catastrophic APS was reported in 1 multiplex APS proband and 4 multiplex AI probands. Proband characteristics are summarized in the Table.

In the multiplex APS families, 1 to 3 family members had APS, and the most common clinical manifestation was thromboembolism. In addition, 8 multiplex APS families also had one or more family members who were affected with other autoimmune disorders, most commonly lupus and rheumatoid arthritis. In the multiplex AI families, 1 to 8 family members were affected by a variety of autoimmune disorders, including lupus, Hashimoto's disease, Sjögren's syndrome, rheumatoid arthritis, myasthenia gravis, type I diabetes mellitus, and other diseases. Affected family members most commonly included siblings and/or parents of the probands.

In the participants enrolled to date, probands with APS who belonged to multiplex APS or multiplex AI families most commonly had primary APS, and thromboembolic complications were the most common clinical manifestation. Families that were multiplex AI were more common than families that included more than one family member affected with APS, and families that were multiplex APS frequently included members that had other autoimmune disorders.

No relevant conflicts of interest to declare.