APS Program Community Q&A Series
APS is a complex disease that is likely caused by several interacting factors. For example, we know that genetics and environmental exposures, such as certain infections at key times, likely contribute to the development of APS. In this edition of the APS Program Community Q&A Series, Dr. Yu (Ray) Zuo discusses the genetics of APS and whether family members of patients with APS should be tested.
While research into the genetics of APS is still at an early stage, it does seem that certain genes you inherit from your parents play some role in the development of abnormal antiphospholipid antibodies. For example, one interesting report described an English Canadian family in which one sister had anticardiolipin antibodies and lupus, while one brother had APS complicated by recurrent blood clots. Fourteen members of the family across three generations eventually underwent clinical and genetic testing. The authors of the study found that immune cell genes HLA-B60 and HLA-DR4 passed down from the father were associated with the presence of anticardiolipin antibodies [1].
Several other genes that regulate our body’s immune homeostasis may also contribute to the development of APS. A study of 133 primary APS patients demonstrated a genetic association between specific changes in the STAT4 and BLK genes and primary APS [2]. Others have suggested that the presence of PTPN22 gene may make a person more susceptible to APS [3]. STAT4, BLK, and PTPN22 are genes that regulate information flow and communication between various immune cells in our body. It is likely that the more of these abnormal genes you inherit from your parents, the higher your risk will be of developing APS at some point in life; however, it is clear that no single gene or even group of related genes tells the whole story.
Because APS is not caused by a single genetic change, it is not commonly passed down from parent to child in the same way that conditions such as cystic fibrosis and sickle cell anemia would be. While having a family member with APS slightly increases the chance your immune system will produce abnormal antibodies, including antiphospholipid antibodies, we do not recommend testing individuals who do not have concerning APS symptoms (such as low platelets, thrombosis, or pregnancy loss). Similarly, we discourage testing asymptomatic children for APS since doing so in the absence of APS signs or symptoms is unlikely to lead to better health outcomes. Rather, we would simply encourage children to be aware of all aspects of their family history, as this can help their doctors make a diagnosis if any early symptoms were to arise.
In summary, current available data support a genetic component to the development of antiphospholipid antibodies and APS; however, it is likely just one part of a highly complex process. More studies (which we will try to participate in) are needed to comprehensively uncover the genetic basis of this relatively rare disease.
Contributed by Yu (Ray) Zuo, MD, MSCS
References:
- Dagenais, P., et al., A family study of the antiphospholipid syndrome associated with other autoimmune diseases. J Rheumatol, 1992. 19(9): p. 1393-6.
- Yin, H., et al., Association of STAT4 and BLK, but not BANK1 or IRF5, with primary antiphospholipid syndrome. Arthritis Rheum, 2009. 60(8): p. 2468-71.
- Ortiz-Fernandez, L. and A.H. Sawalha, Genetics of Antiphospholipid Syndrome. Curr Rheumatol Rep, 2019. 21(12): p. 65.
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