What is Lymphocyte Immunization Therapy in APS?
Lymphocyte immunization therapy (LIT) is an experimental immunomodulatory treatment involving injection of paternal or third-party donor lymphocytes to induce maternal immune tolerance, but it is not recommended or supported by current guidelines for antiphospholipid antibody syndrome (APS) in pregnancy.
Historical Context and Mechanism
Lymphocyte immunotherapy emerged in the early 1980s as a proposed treatment for couples with recurrent miscarriages, based on the theory that some pregnancy losses result from inadequate maternal immune tolerance to paternal antigens 1. The treatment involves injecting processed lymphocytes (white blood cells) from the partner or a donor into the pregnant woman, with the goal of stimulating blocking antibodies and regulatory immune responses 1.
Current Evidence and Guidelines
The established treatment for obstetric APS is combined low-dose aspirin (81-100 mg daily) and prophylactic-dose heparin (usually low-molecular-weight heparin) throughout pregnancy and postpartum, not lymphocyte immunotherapy 2, 3. This standard therapy has demonstrated efficacy in improving live birth rates in women with APS-related pregnancy complications 2.
Why LIT is Not Recommended for APS:
No guideline support: Major rheumatology and obstetric guidelines (EULAR 2017, ACR 2020) make no mention of lymphocyte immunotherapy as a treatment option for APS in pregnancy 2
Different mechanism: APS is caused by antiphospholipid antibodies that induce thrombosis and placental insufficiency through vascular mechanisms, not by inadequate immune tolerance to paternal antigens 4, 5
Weak evidence base: Most studies supporting LIT are quasi-experimental with few randomized, double-blind trials (Level III evidence), and the evidence is primarily for unexplained recurrent miscarriage, not APS specifically 1
Standard APS Management in Pregnancy
For pregnant women meeting criteria for obstetric APS, the strongly recommended treatment is 2, 3:
- Low-dose aspirin (81-100 mg daily) starting before 16 weeks gestation
- Prophylactic-dose LMWH (e.g., enoxaparin 40 mg daily) throughout pregnancy
- Continue both medications through delivery and for 6 weeks postpartum 6
For pregnant women with thrombotic APS, escalate to therapeutic-dose LMWH plus low-dose aspirin 2, 3.
Critical Distinction
LIT addresses a completely different pathophysiology than APS. While LIT theoretically targets alloimmune mechanisms in unexplained recurrent pregnancy loss, APS involves autoimmune antibodies causing thrombosis and placental vascular complications 4, 5. The proven treatment for APS targets the thrombotic mechanism with anticoagulation and antiplatelet therapy 2, 3.