# Evaluation of neutrophil activation in autoimmune kidney diseases using blood heparin-binding protein: a pilot study

**Authors:** Zhen-jun Zhao, Xin-yue Shi, Hong-shan Chen, Hao-miao Zhang, Ying Gao, Ming-xuan Gao, Chen-xi Cai, Zi-rui Liu, Jun-ya Jia, Peng-cheng Xu

PMC · DOI: 10.3389/fmed.2026.1727663 · Frontiers in Medicine · 2026-02-04

## TL;DR

This pilot study explores blood heparin-binding protein (HBP) as a marker for neutrophil activation in autoimmune kidney diseases, finding it to be elevated across various conditions and independent of kidney function.

## Contribution

The study introduces blood HBP as a novel, eGFR-independent marker for neutrophil activation in autoimmune kidney diseases.

## Key findings

- Blood HBP levels were significantly elevated in all autoimmune kidney diseases tested.
- HBP showed higher sensitivity than NGAL, neutrophil counts, and C-reactive protein in detecting neutrophil activation.
- HBP levels correlated with disease activity markers like hematuria and proteinuria in specific conditions.

## Abstract

Currently, there is limited understanding about the activation of neutrophils in autoimmune kidney diseases. Heparin-binding protein (HBP) is a protein in neutrophil granules and has been widely used as a marker for infectious diseases. This study aims to explore the use of blood HBP to evaluate neutrophil activation in autoimmune kidney diseases.

A total of 70 patients diagnosed with autoimmune kidney diseases were enrolled, including 20 with anti-neutrophil cytoplasmic antibodies-associated vasculitis (AAV), 17 with membranous nephropathy (MN), 17 with IgA nephropathy (IgAN), and 16 with minimal change disease (MCD)/focal segmental glomerulosclerosis (FSGS). The control group consisted of 18 patients with sepsis, 20 patients on maintenance hemodialysis, and 20 healthy volunteers. Clinical and laboratory indicators were collected, and the blood HBP were measured.

The blood HBP were significantly elevated in all kinds of autoimmune kidney disease, with the highest levels in AAV and the lowest in MCD/FSGS. Unlike blood NGAL, blood HBP was not affected by estimated glomerular filtration rate (eGFR). Blood HBP was independently correlated with blood neutrophil counts, and its sensitivity was higher than that of blood NGAL, neutrophil counts, and C-reactive protein. In AAV, blood HBP was associated with hematuria, and its levels significantly decreased after remission. In MN and MCD/FSGS, elevated HBP was associated with higher levels of proteinuria. There was a positive correlation between blood HBP and urine HBP in patients with autoimmune kidney diseases.

Blood HBP is a valuable and eGFR-independent marker of neutrophil activation. This study preliminarily reveals that neutrophil activation is widespread in various autoimmune kidney diseases and may be involved in the pathogenesis of these diseases.

## Linked entities

- **Proteins:** LCN2 (lipocalin 2)
- **Diseases:** membranous nephropathy (MONDO:0005376), IgA nephropathy (MONDO:0005342), minimal change disease (MONDO:0006835), focal segmental glomerulosclerosis (MONDO:0100313)

## Full-text entities

- **Genes:** CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, ICAM1 (intercellular adhesion molecule 1) [NCBI Gene 3383] {aka BB2, CD54, P3.58}, NPHS1 (NPHS1 adhesion molecule, nephrin) [NCBI Gene 4868] {aka CNF, NPHN, nephrin}, AZU1 (azurocidin 1) [NCBI Gene 566] {aka AZAMP, AZU, CAP37, HBP, HUMAZUR, NAZC}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, IL22 (interleukin 22) [NCBI Gene 50616] {aka IL-21, IL-22, IL-D110, IL-TIF, ILTIF, TIFIL-23}, KRT20 (keratin 20) [NCBI Gene 54474] {aka CD20, CK-20, CK20, K20, KRT21}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, LCN2 (lipocalin 2) [NCBI Gene 3934] {aka 24p3, MSFI, NGAL, p25}, IGHA1 (immunoglobulin heavy constant alpha 1) [NCBI Gene 3493] {aka IgA1}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, CD79A (CD79a molecule) [NCBI Gene 973] {aka IGA, IGAlpha, MB-1, MB1}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, SELE (selectin E) [NCBI Gene 6401] {aka CD62E, ELAM, ELAM1, ESEL, LECAM2, selectin-e}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}, IL23A (interleukin 23 subunit alpha) [NCBI Gene 51561] {aka IL-23, IL-23A, IL23P19, P19, SGRF}, CCR2 (C-C motif chemokine receptor 2) [NCBI Gene 729230] {aka CC-CKR-2, CCR-2, CCR2A, CCR2B, CD192, CKR2}, LYZ (lysozyme) [NCBI Gene 4069] {aka AMYLD5, LYZF1, LZM}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, MPO (myeloperoxidase) [NCBI Gene 4353], VCAM1 (vascular cell adhesion molecule 1) [NCBI Gene 7412] {aka CD106, INCAM-100}
- **Diseases:** Organ Failure (MESH:D009102), autoimmune (MESH:D001327), FSGS (MESH:D005923), sclerosis (MESH:D012598), NETs (MESH:C536657), Henoch-Schonlein purpura (MESH:D011695), IGAN (MESH:D005922), proteinuria (MESH:D011507), lupus (MESH:D008180), chronic liver disease (MESH:D008107), inflammation (MESH:D007249), T-cell dysfunction (MESH:C536780), AAV (MESH:D014657), SSNS (MESH:D009404), hematuria (MESH:D006417), malignant neoplasm (MESH:D009369), endothelial dysfunction (MESH:D014652), ANCA-associated vasculitis (MESH:D056648), renal function decline (MESH:D060825), renal insufficiency (MESH:D051437), MCD (MESH:D009402), H-sC (MESH:C535687), hepatitis B virus infection (MESH:D006509), galactose-deficient IgA1 (MESH:D005693), Autoimmune kidney diseases (MESH:D007674), bacterial infections (MESH:D001424), MN (MESH:D015433), Septic Shock (MESH:D012772), infectious diseases (MESH:D003141), Sepsis (MESH:D018805), glomerulonephritis (MESH:D005921), X-yS (MESH:D000326), NC (MESH:C564275), VTEs (MESH:D054556), immune abnormalities (MESH:D007154), end-stage renal disease (MESH:D007676), infection (MESH:D007239)
- **Chemicals:** biotin (MESH:D001710), pyridinoline (MESH:C015484), TMB (MESH:C021758), steroid (MESH:D013256), ATP (MESH:D000255), calcium (MESH:D002118), creatinine (MESH:D003404), NC (-), sodium citrate (MESH:D000077559)
- **Species:** Methylobacillus methanolivorans (species) [taxon 1848927], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12913169/full.md

## References

34 references — full list in the complete paper: https://tomesphere.com/paper/PMC12913169/full.md

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Source: https://tomesphere.com/paper/PMC12913169