Serum B-Cell Activating Factor Levels in Pregnant Women With Antiphospholipid Antibodies and Previous Adverse Outcomes: What the Research Shows

For many women, pregnancy is a time of hope—but for those with autoimmune conditions like antiphospholipid syndrome (APS), the risk of complications (such as miscarriage, preeclampsia, or fetal growth restriction) is much higher. Antiphospholipid antibodies (aPLs)—proteins that attack healthy cells in blood vessels and the placenta—are a key driver of these risks. But scientists are still untangling the why: What biological signals link aPLs to poor pregnancy outcomes?

One molecule gaining attention is B-cell activating factor (BAFF), a protein critical for keeping B cells (the immune cells that make antibodies) alive and functioning. While BAFF is known to be elevated in thrombotic APS (where blood clots form), little research has looked at BAFF in pregnant women with aPLs and a history of adverse pregnancy outcomes (APOs—like miscarriage or preterm birth). A 2020 study from researchers at Peking University Third Hospital aimed to fill that gap—and its findings could change how we predict and treat high-risk pregnancies.

What Is BAFF, and Why Does It Matter for Pregnancy?

BAFF (also called BLyS) is part of the tumor necrosis factor (TNF) superfamily. It’s made by immune cells like neutrophils, T cells, and dendritic cells, and it helps B cells mature, survive, and produce antibodies—including autoantibodies like aPLs. In autoimmune diseases like lupus, high BAFF levels are linked to more severe symptoms because they fuel the overactivation of B cells.

During normal pregnancy, BAFF levels drop—a likely adaptation to prevent the immune system from attacking the fetus (a “foreign” tissue). But in women with aPLs, this balance might be broken. Could high BAFF levels signal a disrupted immune response that puts pregnancies at risk?

The Study: Who, How, and What They Measured

The research team enrolled 36 pregnant women with two key risk factors:

Positive aPLs (IgG/IgM anti-cardiolipin antibodies, anti-β2 glycoprotein I antibodies, or lupus anticoagulant, confirmed twice)
A history of APOs (early miscarriage <10 weeks, late miscarriage ≥10 weeks, preeclampsia, or fetal growth restriction)

They compared these women to two control groups:

25 healthy pregnant women (no aPLs, no prior APOs)
35 healthy non-pregnant women (no chronic illnesses)

All participants provided blood samples during the first trimester (when APO risks are highest). The team measured:

BAFF levels (via ELISA)
Interferon-alpha (IFN-α)—a cytokine linked to autoimmune inflammation
Other cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, TNF-α)—signals that regulate immune activity

After delivery or pregnancy loss, they grouped the aPL-positive women by their outcomes:

APOs: 12 women who had another adverse event (miscarriage, preeclampsia, preterm birth, etc.)
NAPOs: 24 women who had a healthy, full-term baby
Fetal loss: 3 women who lost the pregnancy
Live birth: 33 women who delivered a healthy baby

Key Findings: BAFF Levels Tell a Story

The results painted a clear picture of how BAFF and immunity interact in high-risk pregnancies:

Healthy pregnancy lowers BAFF—for good reason
Healthy pregnant women had significantly lower BAFF levels (245 pg/mL median) than healthy non-pregnant women (327 pg/mL). This supports the idea that low BAFF helps maintain maternal-fetal immune tolerance—preventing the mother’s immune system from rejecting the fetus.
aPL-positive women have higher BAFF than healthy pregnant women
The aPL-positive group had a median BAFF level of 308 pg/mL—26% higher than healthy pregnant women. Why? High BAFF could be fueling the survival of auto reactive B cells, which make the aPLs that damage the placenta and blood vessels.
Women with new APOs had the highest BAFF
Among aPL-positive women, those who experienced another adverse outcome (APOs group) had a median BAFF level of 417 pg/mL—61% higher than women who had a healthy baby (NAPOs group: 259 pg/mL). This suggests BAFF could be a biomarker for pregnancy risk: the higher the BAFF, the greater the chance of complications.
Cytokine imbalances point to inflammation
Compared to healthy pregnant women, aPL-positive women had:
- Higher levels of pro-inflammatory cytokines: IFN-α (33 vs 13 pg/mL), IL-6 (39 vs 3 pg/mL), TNF-α (8 vs 2 pg/mL)
- Lower levels of IL-17A (5 vs 12 pg/mL)—a cytokine that helps regulate immune responses
Importantly, BAFF levels correlated strongly with IL-6 (r=0.525, p=0.002) and IL-10 (r=0.438, p=0.012). IL-6 drives inflammation, while IL-10 is an anti-inflammatory signal—this mix suggests a confused immune system that’s both overactive and trying to compensate.

What Do These Results Mean for Women With aPLs?

The study adds three critical pieces to the puzzle of autoimmune pregnancy risks:

1. BAFF is a key player in aPL-related APOs

High BAFF levels likely contribute to the cycle of B-cell overactivation → aPL production → placental damage. For women with prior APOs, measuring BAFF in the first trimester could help doctors predict who is at highest risk of another complication.

2. Inflammation drives poor outcomes

The higher levels of IFN-α, IL-6, and TNF-α in aPL-positive women confirm that chronic inflammation is a major factor in APOs. BAFF may be both a cause and a result of this inflammation: it fuels B cells to make aPLs, which then trigger more immune activation.

3. BAFF could be a new treatment target

Drugs like belimumab (which blocks BAFF) are already used to treat lupus and some cases of APS. This study suggests belimumab might help women with aPLs by lowering BAFF, reducing autoantibody production, and calming inflammation. More research is needed, but this is a promising lead.

Limitations and Next Steps

Like all studies, this one has caveats:

Small sample size: Only 36 aPL-positive women, and just 3 had fetal loss. Larger studies are needed to confirm BAFF’s role in rare outcomes.
No dynamic testing: BAFF levels were measured only once (first trimester). Tracking BAFF throughout pregnancy could show how it changes with risk.
Exclusions: Women with other autoimmune diseases (like lupus) were excluded, so results may not apply to everyone with aPLs.

The researchers note that future work should look at BAFF levels in more diverse groups and test whether lowering BAFF (via drugs or lifestyle) improves pregnancy outcomes.

Final Thoughts

For women with a history of aPLs and adverse pregnancies, this study offers hope: BAFF could be the “red flag” doctors need to identify high-risk cases early. It also opens the door to treatments that target the immune system’s root causes—instead of just managing symptoms.

As one of the first studies to link BAFF to aPL-related pregnancy risks, this research from Peking University Third Hospital adds important context to the complex interplay between autoimmunity and reproduction. For women navigating the fear of another pregnancy loss, it’s a step toward more personalized, effective care.

Original study by Xin-Yi Li, Hong-Ji Duan, Xiang-Yuan Liu, and Xiao-Li Deng, Department of Rheumatology and Immunology, Peking University Third Hospital, published in Chinese Medical Journal (2020).
doi: 10.1097/CM9.0000000000000948
Full study available at: doi.org/10.1097/CM9.0000000000000948

Was this helpful?

0 / 0