Lupus and recurrent pregnancy loss: the role of female sex hormones and B cells

Abstract

Systemic lupus erythematosus is a debilitating autoimmune disease characterized by uncontrolled activation of adaptive immunity, particularly B cells, which predominantly affects women in a 9 to 1 ratio compared to men. This stark sex disparity strongly suggests a role for female sex hormones in the disease’s onset and progression. Indeed, it is widely recognized that estradiol not only enhances the survival of autoreactive B cells but also stimulates the production of autoantibodies associated with systemic lupus erythematosus, such as anti-nuclear antibodies and anti-dsDNA antibodies. Clinical manifestations of systemic lupus erythematosus typically emerge after puberty and persist throughout reproductive life. Furthermore, symptoms often exacerbate during the premenstrual period and pregnancy, as increased levels of estradiol can contribute to disease flares. Despite being fertile, women with lupus face a heightened risk of pregnancy-related complications, including pregnancy loss and stillbirth, which significantly surpass the rates observed in the healthy population. Therefore, this review aims to summarize and discuss the existing literature on the influence of female sex hormones on B-cell activation in patients with systemic lupus erythematosus, with a particular emphasis on their impact on pregnancy loss.

Landscape of gut mucosal immune cells showed gap of follicular or memory B cells into plasma cells in immunological non‐responders

“…Thus, the findings in this study may not apply to heterosexual male patients. In addition, female sex hormones such as estradiol, 48 estrogen, and progesterone, 49 also contribute to B‐cell function by activating the Tfh/B‐cell axis. Thus, the results of this study may not be generalizable to female cases.…”

Association of Anti-Ro/SSA and Anti-La/SSB Autoantibodies With Pregnancy Outcome in the General Population

“…The mechanism of tolerance is based on the elimination or inactivation of cells that can react against the organism itself. The loss of immune tolerance results in the dysfunction of the immune system and, by extension, the appearance of autoimmune diseases ( 20 ). Autoantibodies recognizing the Ro and La proteins of the small ribonuclei are frequently detected in the sera of patients with autoimmune rheumatic diseases and are particularly relevant in primary Sjögren’s syndrome.…”

“…Patients exhibiting signs and symptoms of connective tissue sickness, particularly those consistent with Sjogren’s syndrome or lupus erythematosus, are evaluated by antinuclear antibody (ANA) testing. These antibodies are checked for using SS-A and SS-B antibodies ( 20 - 22 ). Sjogren’s syndrome is characterized by reduced secretion and eventual destruction of the exocrine glands, leading to dryness of the mucous membranes and conjunctiva.…”