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Open research questions in Systemic Lupus Erythematosus Research

612 gap statements mined from Systemic Lupus Erythematosus Research papers in our 7.9M-paper local library, which holds 2,946 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • Limited population-level evidence on postoperative outcomes in SLE. Poorly characterized interaction between surgical trauma and preexisting immune dysregulation in SLE patients. Lack of robust evidence on lupus-specific perioperative risk.

    Higher postoperative complication rates in patients with systemic lupus erythematosus undergoing surgical and obstetric procedures: a nationwide retrospective matched cohort study · 2026 · DOI

  • Further studies are needed to confirm the findings and to explore the role of anti-DFS70 antibodies in the differentiation of UCTD to CTD. Studies should investigate the correlation between anti-DFS70 antibodies and other CTD-specific autoantibodies. Research should focus on the clinical significance of anti-DFS70 antibodies in patients with UCTD.

    Clinical and serological features according to anti-DFS70 antibody status in undifferentiated connective tissue disease: a retrospective cross-sectional study · 2026 · DOI

  • The study aims to address this gap by comparing clinical and serological features between anti-DFS70-positive and -negative patients with UCTD.

    Clinical and serological features according to anti-DFS70 antibody status in undifferentiated connective tissue disease: a retrospective cross-sectional study · 2026 · DOI

  • Elucidating the precise events that trigger the loss of tolerance and subsequent autoimmunity remains a major investigative challenge. Understanding the interplay among OS, gut dysbiosis, and immune dysregulation is crucial for developing effective therapies.

    The Gut Microbiota and Oxidative Stress as Converging Mechanisms in Environmental Chemical-Mediated Systemic Lupus Erythematosus · 2026 · DOI

  • The physiological elevation of D-dimer during pregnancy limits its utility in this population. The need to distinguish between physiological and pathological elevations of D-dimer during pregnancy.

    Fibrin Monomer and Systemic Lupus Erythematosus Reactivation During Pregnancy: A Retrospective Study · 2025 · DOI

  • There is a need to understand the dysregulated epigenetic mechanisms in the immune system. The current understanding of the pathogenesis of SLE is incomplete, and epigenetic factors have not been fully explored. The relationship between epigenetic changes and immune responses in SLE is not well understood.

    Epigenetic Dysregulation in the Pathogenesis of Systemic Lupus Erythematosus · 2024 · DOI

  • There is a lack of understanding of the roles of B and T lymphocytes in the pathogenesis of SLE and Lupus Nephritis. The multifaceted mechanisms and interactions of lymphocytes in SLE and Lupus Nephritis are not well understood. The phenotypic and functional dysregulations of B and T lymphocytes in SLE and Lupus Nephritis are not well characterized.

    Lymphocytes Change Their Phenotype and Function in Systemic Lupus Erythematosus and Lupus Nephritis · 2024 · DOI

  • Until further evidence emerges, caution is warranted in ascribing disease association to heterozygous genotypes in TNIP1, P2RY8, BLK, BANK1, and SH2B3, and linkage to patients in clinical pedigrees should not be taken as inferring a monoallelic inborn error of immunity.

    Disease associations for rare immune genetic variants require statistical or rule-based support · 2026 · DOI

  • Whether use of IL-17 inhibitors increase the risk of systemic lupus erythematosus (SLE) remains unclear.

    Interleukin-17 Inhibitors and the Potential Association of Systemic Lupus Erythematosus · 2026 · DOI

  • Vitamin K antagonists (VKA) are the recommended treatment for thrombotic antiphospholipid syndrome (TAPS), but it remains uncertain whether direct oral anticoagulants (DOAC) could serve as an alternative to VKA in a subgroup of low-risk TAPS patients with venous thromboembolism (VTE).

    Effectiveness and safety of direct oral anticoagulants in patients with thrombotic antiphospholipid syndrome and venous thrombosis: A retrospective cohort study · 2026 · DOI

  • However, specific clinical treatments to mitigate neuroinflammation associated with NPSLE are currently lacking.

    ShenQi DiHuang Decoction (SQDHD) Ameliorates Neuroinflammation and Neuropsychiatric Manifestations in Pristane Induced Lupus Mice via Blocking JAK1‐STAT3 Pathway · 2026 · DOI

  • Although paediatric patients were underrepresented in the pivotal trials, the drug’s efficacy and safety in adults suggest potential benefits for younger patients, warranting further investigation and potential off-label use.

    Single-center experience of voclosporin use for pediatric lupus nephritis: a case series · 2026 · DOI

  • A limitation of this study is the small sample size and observational design, as well as the use of each patient as an internal control pre- and post-voclosporin while on standard of care therapies.

    Single-center experience of voclosporin use for pediatric lupus nephritis: a case series · 2026 · DOI

  • Ethnicity-related inequalities in the epidemiology of systemic lupus erythematosus (SLE) have been consistently described, yet robust population-level data remain limited.

    The incidence, mortality and complications of systemic lupus erythematosus: a population-level cohort study from 2012 to 2023 · 2026 · DOI

  • The clinical significance of acquired resistance to activated protein C (APCr) and antibodies against protein C (anti-PCs) in APS has not been established.

    Prevalence and prognostic value of activated protein C resistance and anti–protein C antibodies in patients with aPLs: an APS ACTION Registry study · 2026 · DOI

  • Although SLE patients are known to have an elevated average risk of severe infection, little is known about how this excess risk varies by patient characteristics.

    Disparities in severe infection risk associated with SLE: evidence from a causal forest analysis · 2026 · DOI

  • Observational data suggest that BEL monotherapy may be effective in selected patients, but comparative real-world evidence is limited.

    Does adding concomitant immunosuppressive therapy to belimumab provide additional benefits in SLE? Results from the BEL-Spain Registry · 2026 · DOI

  • In clinical practice, BEL is frequently combined with conventional immunosuppressants (IS), but the added benefit of concomitant IS once disease control is achieved remains uncertain.

    Does adding concomitant immunosuppressive therapy to belimumab provide additional benefits in SLE? Results from the BEL-Spain Registry · 2026 · DOI

  • A core set of patient-reported outcomes (PROs) for systemic lupus erythematosus (SLE) has not been established, and no studies have compared predictive validity of disease-specific and generic quality of life (QOL) instruments.

    Comparison of predictive validity of the Lupus Patient-Reported Outcome and Short-Form-12 for damage accrual in systemic lupus erythematosus · 2026 · DOI

  • The limited follow-up precluded assessment of an established renal response. The patient had multiple health issues, including hyperthyroidism, SLE, and LN, which made treatment challenging.

    Case Report: A rare case of biopsy-proven lupus nephritis complicated by Graves’ disease in a 39-year-old man · 2026 · DOI

  • The evidence is mixed, - Studies often lack comparators and standardised assays, - The link between viral persistence and autoantibody production is not…

    Systemic lupus erythematosus and related autoimmune manifestations in people living with HIV-1 in the antiretroviral therapy era: phenotypes, mechanisms and clinical implications · 2026 · DOI

  • Studies measuring tissue interferon signatures in people with HIV on ART in relation to autoantibody status are needed, - Research on the link between viral persistence and autoantibody production…

    Systemic lupus erythematosus and related autoimmune manifestations in people living with HIV-1 in the antiretroviral therapy era: phenotypes, mechanisms and clinical implications · 2026 · DOI

  • The follow-up was limited, - The study was a single case report, - There is no established guideline for managing cases of co-occurrence of GD…

    Case Report: A rare case of biopsy-proven lupus nephritis complicated by Graves’ disease in a 39-year-old man · 2026 · DOI

  • The study was retrospective, - the sample size was relatively small, - barriers in healthcare access during the pandemic may have limited patients' access to specialized…

    Prevalence and Risk Factors of Acute Ischemic Stroke in Patients with Antiphospholipid Syndrome: A Retrospective Monocenter Analysis · 2025 · DOI

  • Further studies are needed to investigate the impact of the COVID-19 pandemic on risk factors associated with acute ischemic stroke, - studies with larger sample sizes are needed to confirm the findings of this study, - research on the pathogenesis of APS and the development of thrombotic events…

    Prevalence and Risk Factors of Acute Ischemic Stroke in Patients with Antiphospholipid Syndrome: A Retrospective Monocenter Analysis · 2025 · DOI

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Open questions raised by papers listed on this page include: (1) Lack of robust evidence on lupus-specific perioperative risk (“Higher postoperative complication rates in patients with systemic lupus…”, 2026); (2) Further studies are needed to confirm the findings and to explore the role of anti-DFS70 antibodies in the differentiation of UCTD to CTD (“Clinical and serological features according to anti-DFS70 antibody status in…”, 2026); (3) Whether use of IL-17 inhibitors increase the risk of systemic lupus erythematosus (SLE) remains unclear (“Interleukin-17 Inhibitors and the Potential Association of Systemic Lupus…”, 2026); (4) Ethnicity-related inequalities in the epidemiology of systemic lupus erythematosus (SLE) have been consistently described, yet robust population-level data remain limited (“The incidence, mortality and complications of systemic lupus erythematosus: a…”, 2026); (5) The clinical significance of acquired resistance to activated protein C (APCr) and antibodies against protein C (anti-PCs) in APS has not been established (“Prevalence and prognostic value of activated protein C resistance and…”, 2026). 612 gap statements have been mined from Systemic Lupus Erythematosus Research papers in our 7.9M-paper local library, which holds 2,946 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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