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Open research questions in Complement system in diseases

93 unresolved questions extracted from the limitations and future-work sections of 291 Complement system in diseases papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • The paper identifies challenges in diagnosing sepsis-associated thrombotic microangiopathy-like syndrome, including its similarity to other conditions. The study highlights the importance of recognizing the distinct characteristics of this syndrome. The authors note the challenges of managing critically ill patients with this condition, including the need for comprehensive sepsis management and supportive care.

    Sepsis-associated thrombotic microangiopathy–like syndrome following cardiac surgery: a case report · 2026 · DOI

  • The paper identifies a gap in the understanding of sepsis-associated thrombotic microangiopathy-like syndrome. There is a need for structured diagnostic differentiation in critically ill patients. The study highlights the importance of recognizing this syndrome as distinct from classic immune-mediated thrombotic thrombocytopenic purpura and overt disseminated intravascular coagulation.

    Sepsis-associated thrombotic microangiopathy–like syndrome following cardiac surgery: a case report · 2026 · DOI

  • Investigate the role of C3aR in other types of cancer, - Examine the relationship between C3aR expression and treatment outcomes, - Explore the potential of C3aR as a therapeutic target

    Complement C3a receptor expression is associated with distinct immune microenvironmental profiles in clear cell renal cell carcinoma · 2026 · DOI

  • The cellular distribution and relationship of C3aR with the immune microenvironment in ccRCC are not well understood. The immune context of C3aR expression in ccRCC has not been fully characterized.

    Complement C3a receptor expression is associated with distinct immune microenvironmental profiles in clear cell renal cell carcinoma · 2026 · DOI

  • The detailed cellular mechanisms underlying PCOS remain elusive. Limited understanding of the molecular and immunological landscape of PCOS.

    RETRACTED: Integrated multi-omics analysis reveals complement component 3 as a central driver of immune dysregulation in polycystic ovary syndrome · 2025 · DOI

  • However, the proteomic signatures linked to CHIP driver mutations and their prognostic implications in HFpEF remain poorly defined.

    Clonal Hematopoiesis of Indeterminate Potential Proteomic Risk Score for Predicting Clinical Outcome in Patients With Heart Failure With Preserved Ejection Fraction · 2026 · DOI

  • The role of the complement system in affecting the phenotype and anti-tumor function of NK cells remains poorly understood.

    Complement C3 deficiency increases the effector and cytotoxic functions of NK cells and suppresses tumor growth · 2026 · DOI

  • Despite its widespread impact, the molecular basis and immunological aspects of PCOS remain insufficiently understood, limiting effective diagnosis and treatment strategies.

    RETRACTED: Integrated multi-omics analysis reveals complement component 3 as a central driver of immune dysregulation in polycystic ovary syndrome · 2025 · DOI

  • Genetic factors are increasingly recognized as contributors to individual susceptibility, yet the specific variants influencing T2DM-associated CHD remain incompletely defined.

    C5L2 gene polymorphisms and their functional interaction with metabolic-inflammatory networks in T2DM-associated CHD: insights from an integrative genetic and clinical analysis in a Chinese population · 2025 · DOI

  • However, the clinical outcome of patients with TMA and SLE treated with sequential therapy between RTX and BEL remains elusive.

    Treatment of thrombotic microangiopathy associated with systemic lupus erythematosus with low-dose rituximab as an induction agent and belimumab as a maintenance agent · 2025 · DOI

  • However, the oligomer structural characteristics of MBL and the pathways involved in immune defense mechanisms remain poorly understood.

    MBL regulates phagocytosis and bactericidal activity of macrophages by triggering AKT/NF-κB/Rab5A axis occurred early in vertebrate evolution · 2025 · DOI

  • However, the role of C3 expressed by tumor cells themselves during oncogenesis remain inadequately characterized.

    Cell-autonomous complement C3 activity in prostate epithelial cells suppresses malignant transformation through tonic restrain of the MYC-tumorigenesis program 3135 · 2025 · DOI

  • The complement system, a crucial component of innate immunity, plays a dual role in pathogen detection and potential immune evasion, yet its interactions with MTBC strains remain underexplored.

    C1q and mannose-binding lectin binding and complement activation across genetically diverse Mycobacterium tuberculosis complex strains · 2025 · DOI

  • However, the relationship between complement activity and MASLD is not yet fully understood.

    Epigenetic alteration of complement genes in MASLD 2772 · 2025 · DOI

  • Relative contributions of C3, FB, and FD to AP activation have not been thoroughly analyzed.

    A small amount of Factor D activates the complement alternative pathway under conditions of higher levels of C3 and Factor B 4351 · 2025 · DOI

  • While C5a neutralization is protective in sepsis and inflammation models, its role in Spn infection remains unclear.

    Synergistic function of C5aR1 and C5aR2 complement receptors in defending against bacterial pneumonia 4441 · 2025 · DOI

  • The underlying neuroimmune mechanisms secondary to trauma that link rmCHI to cognitive impairment remain to be elucidated, and the contribution of the complement system to the pathological sequelae of this type of brain injury is unexplored.

    Targeted complement inhibition ameliorates the pathological and cognitive outcomes in repetitive mild closed head injury · 2025 · DOI

  • Yet, data on the to which extent complement, and more specifically the alternative complement pathway, is activated in patients with carotid atherosclerosis and related to adverse outcome in these patients, are scarce.

    Alternative Complement Pathway in Carotid Atherosclerosis: Low Plasma Properdin Levels Associate With Long‐Term Cardiovascular Mortality · 2025 · DOI

  • Currently treatment modalities for preventing and treating post KTx C3G recurrence (plasma exchange, rituximab and eculizumab) in adults have yielded inconsistent results.

    Childhood onset C3 glomerulopathy: recurrence after kidney transplantation—a case series · 2024 · DOI

  • The role of CD59 in cancer growth and interactions between CD59 and immune cells that modulate immune evasion has not been well explored.

    Deciphering CD59: Unveiling Its Role in Immune Microenvironment and Prognostic Significance · 2024 · DOI

  • Although the underlying mechanisms are not well defined, GT103 targets a conformationally distinct CFH epitope that is created when CFH is associated with tumor cells, kills tumor cells in vitro, and has potent antitumor activity in vivo.

    Promotion of an Antitumor Immune Program by a Tumor-specific, Complement-activating Antibody · 2024 · DOI

  • However, the evolutionary origins of immune defense of CL-K1 and its mechanism in clearance of pathogenic microorganisms remain unclear, especially in early vertebrates.

    CL-K1 Promotes Complement Activation and Regulates Opsonophagocytosis of Macrophages with CD93 Interaction in a Primitive Vertebrate · 2024 · DOI

  • However, the mechanism by which ISG65 reduces C3b function has not been determined.

    Molecular mechanism of complement inhibition by the trypanosome receptor ISG65 · 2024 · DOI

  • The rarity of severe AKI as a presentation of PNH. The diagnostic challenge when atypical features are present.

    Paroxysmal nocturnal hemoglobinuria with a positive Coombs test presenting as acute kidney injury: a case report · 2026 · DOI

  • There is a lack of understanding of the neurological impact of caplacizumab in refractory iTTP survivors. Prior studies have not investigated the effect of caplacizumab on blood-brain barrier integrity and cognitive outcomes in this population.

    Neurological Impact of Caplacizumab in Refractory iTTP Survivors: A Comparative Study of Blood-Brain-Barrier Integrity and Cognitive Outcomes · 2026 · DOI

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93 open questions have been extracted from the limitations and future-work passages of 291 Complement system in diseases papers in our 4.5M-paper local library. Each one below links back to the study that raised it, so you can read the original claim in context.

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