Connective tissue disorders, also termed collagen vascular disorders, have two basic underlying causes. First are the immune-complex diseases, in which deposition of immune complexes causes connective tissue damage. Because these manifest by sterile inflammation—predominantly of the skin, joints, blood vessels, and kidneys—they are referred to as rheumatic diseases. Many of these immune-complex diseases are more prevalent in women, and systemic lupus erythematosus (SLE) and rheumatoid arthritis are examples. Second are the inherited disorders that involve bone, skin, cartilage, blood vessels, and basement membranes. These include Marfan syndrome, osteogenesis imperfecta, and Ehlers-Danlos syndrome.
IMMUNE-MEDIATED CONNECTIVE TISSUE DISEASES
These disorders can be separated into those associated with and those without autoantibody formation. The rheumatoid factor is an autoantibody found in many autoimmune inflammatory conditions such as SLE, rheumatoid arthritis, systemic sclerosis (scleroderma), mixed connective tissue disease, dermatomyositis, polymyositis, and various vasculitis syndromes. Instead, the RF-seronegative spondyloarthropathies are strongly associated with expression of the antigen termed human leukocyte antigen B27 (HLA-B27). These include ankylosing spondylitis, psoriatic arthritis, Reiter disease, and other arthritis syndromes.
The normal immunosuppression of pregnancy that allows and is essential for successful engraftment of fetal and placental tissues may mitigate activity in some of these syndromes. First, estrogens upregulate and androgens downregulate T-cell response, and progesterone is immunosuppressive (Abdul Hussain, 2020; Robinson, 2012). Second, pregnancy induces a predominance of T2 helper cells compared with cytokine-producing T1 helper cells (Petri, 2019). These changes are discussed in detail in Chapter 4 (p. 61).
However, active immune-mediated disease may contribute to obstetrical complications (Kither, 2020). One longitudinal cohort study found that unrecognized autoimmune systemic rheumatic disorders are associated with significant risk for preeclampsia and fetal-growth restriction (Spinillo, 2016). In this study, the prevalence of unrecognized systemic rheumatic diseases approximated 0.3 percent, and preeclampsia or fetal-growth restriction complicated 25 percent of these pregnancies.
Last, some immune-mediated diseases may be either caused or activated as a result of prior pregnancies. To explain, fetal cells and cell-free DNA are detectable in maternal blood beginning early in pregnancy (Simpson, 2013; Waldorf, 2008). Fetal cell microchimerism is the persistence of fetal cells in the maternal circulation and in organs following pregnancy. These fetal cells may become engrafted in maternal tissues and stimulate production of autoantibodies. Evidence for this includes fetal stem cells engrafted in tissues in women with autoimmune thyroiditis and systemic sclerosis (Jimenez, 2005; Srivatsa, 2001). Such microchimerism has also been described in women with SLE and those with rheumatoid arthritis–associated HLA alleles (da Silva, 2016; Lee, 2010). Conversely, engrafted maternal cells may provoke autoimmune conditions in a woman’s offspring (Stevens, 2016; Ye, 2012).
SYSTEMIC LUPUS ERYTHEMATOSUS
This autoimmune disease has an intricate pathogenesis that results from interactions between susceptibility genes and environmental factors (Hahn, 2018...