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Background and objectives <p>Genetic investigations have associated APOL1 risk alleles (G1/G2) with lupus nephritis (LN) and, paradoxically, protection against <i>Trypanosoma brucei</i> infection. This review aims to elucidate their&#xa0;shared pathogenic mechanisms by investigating <i>T. brucei</i> infection processes and how G1/G2 risk variants influence cellular membranes of leukocytes and endothelial cells, impacting leukocyte migration, a relevant factor in LN pathogenesis.</p> Design <p>A scoping review was conducted by formulating research questions and systematically searching the PubMed and Cochrane databases using relevant MeSH terms and keywords. Inclusion criteria comprised English language studies published between 2000 and March 2025, aligning with the conceptual framework.</p> Results <p>The publications reported were split between primary (53.7%) and secondary studies (46.3%). Primary studies were mostly of high quality (17/22), three of moderate quality, and one of low quality.</p> Conclusions <p>APOL1 G1/G2 alleles lead to reduced phosphatidylinositol-4-phosphate (PI4P) levels, altering cholesterol homeostasis in cell membranes. This impacts endothelial cell function and may impede <i>T. brucei</i> extravasation. Similarly, impaired leukocyte diapedesis potentially promotes an innate immune response, contributing to LN pathogenesis. Viral co-infections can further exacerbate these processes. Understanding these shared mechanisms holds the potential to form a precision medicine approach in LN management. However, further experimental research, particularly involving human subjects, is warranted to validate these theoretical possibilities.</p>

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Apolipoprotein L1 risk alleles: extravasation of T. brucei and insights into lupus nephritis pathogenicity—a scoping review

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月4日

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  • George N. Zsidisin,
  • Andreas Politis

摘要

Background and objectives

Genetic investigations have associated APOL1 risk alleles (G1/G2) with lupus nephritis (LN) and, paradoxically, protection against Trypanosoma brucei infection. This review aims to elucidate their shared pathogenic mechanisms by investigating T. brucei infection processes and how G1/G2 risk variants influence cellular membranes of leukocytes and endothelial cells, impacting leukocyte migration, a relevant factor in LN pathogenesis.

Design

A scoping review was conducted by formulating research questions and systematically searching the PubMed and Cochrane databases using relevant MeSH terms and keywords. Inclusion criteria comprised English language studies published between 2000 and March 2025, aligning with the conceptual framework.

Results

The publications reported were split between primary (53.7%) and secondary studies (46.3%). Primary studies were mostly of high quality (17/22), three of moderate quality, and one of low quality.

Conclusions

APOL1 G1/G2 alleles lead to reduced phosphatidylinositol-4-phosphate (PI4P) levels, altering cholesterol homeostasis in cell membranes. This impacts endothelial cell function and may impede T. brucei extravasation. Similarly, impaired leukocyte diapedesis potentially promotes an innate immune response, contributing to LN pathogenesis. Viral co-infections can further exacerbate these processes. Understanding these shared mechanisms holds the potential to form a precision medicine approach in LN management. However, further experimental research, particularly involving human subjects, is warranted to validate these theoretical possibilities.