Systematically review the literature to evaluate if antibody-antigen complexes significantly contribute to stroke risk, particularly in patients diagnosed with autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), as well as individuals receiving intravenous immunoglobulin (IVIg) therapy.

Strokes are the second leading cause of death among non-infectious diseases, according to the Global Burden of Disease in 2021. A stroke occurs when an artery in the brain ruptures or becomes blocked and can be classified as hemorrhagic or ischemic, respectively. While conditions such as RA and SLE are not traditional risk factors for stroke, we consider their auto antibodies to be contributory to stroke risk. Further, intravenous immunoglobulin (IVIg) infusion has been associated with stroke following infusion. Here, we conduct a systematic review to further investigate the role of antibody-antigen complexes in stroke risk.

Following PRISMA guidelines, we searched the PubMed database from 2000-2025 for research articles and reviews on the prevalence of stroke in patients with RA or SLE and those receiving IVIg. Eligible studies included observational studies and meta-analyses reporting on stroke prevalence in these groups.

64 articles met inclusion criteria. Reports showed RA and SLE increased patients’ risk of stroke, though the exact caliber varies. However, many studies failed to account for known confounders such as diabetes, atrial fibrillation and smoking making a correlation difficult to determine. In IVIg-treated patients, case reports describe patients’ strokes within a few days, even 24hrs, of infusion, suggesting a temporal link, though causality remains unclear.

The influence of non-traditional risk factors on stroke risk is critically understudied. Preliminary data suggest antibody-antigen complexes – whether autoimmune or treatment mediated – may exacerbate the chance of stroke, but further investigation should be conducted to study their interaction with well-studied traditional risk factors.