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Peer-reviewedCC BY 4.0Frontiers in Immunology

Pretreatment neutrophil-to-lymphocyte ratio is associated with clinical phenotypes and infection-related mortality in microscopic polyangiitis: the multicentre REVEAL cohort study

  • Muneyuki Hatta1
  • Ryu Watanabe1
  • Mayu Shiomi1
  • Yuichi Masuda2
  • Ayana Okazaki2
  • Shogo Matsuda2
  • Takuya Kotani2
  • Tomoki Taniguchi3
  • Shingo Iwasaka3
  • Keiichiro Kadoba3
  • Atsushi Manabe3
  • Kaho Jo4
10 more authors
  • Youhei Fujiki4
  • Hirofumi Miyake5
  • Hideki Oka6
  • Shuji Sumitomo6
  • Wataru Yamamoto7
  • Shinya Nakatani8
  • Akihiro Tsuda9
  • Tetsuya Watanabe10
  • Kazuhisa Asai10
  • Motomu Hashimoto1
10 affiliations
  1. 1Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine
  2. 2Department of Internal Medicine (IV), Osaka Medical and Pharmaceutical University
  3. 3Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University
  4. 4Division of Clinical Immunology and Rheumatology, Yodogawa Christian Hospital
  5. 5Department of General Internal Medicine, Tenri Hospital
  6. 6Department of Rheumatology, Kobe City Medical Center General Hospital
  7. 7Department of Health Information Management, Kurashiki Sweet Hospital
  8. 8Department of Nephrology, Osaka Metropolitan University Graduate School of Medicine
  9. 9Department of Metabolism, Endocrinology and Molecular Medicine, Osaka Metropolitan University Graduate School of Medicine
  10. 10Department of Respiratory Medicine, Osaka Metropolitan University Graduate School of Medicine
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Abstract

Background: Microscopic polyangiitis (MPA) remains associated with substantial early mortality despite advances in immunosuppressive therapy, highlighting the need for simple biomarkers that facilitate LR) has been associated with disease activity and prognosis in antineutrophil cytoplasmic antibody-associated vasculitis (AAV), its phenotype-specific significance in newly diagnosed MPA remains unclear. We investigated whether pretreatment NLR is associated with clinical phenotype, disease course, and long-term outcomes in MPA.

Methods: Among 418 patients with MPA enrolled in the multicentre REVEAL cohort between 2005 and 2025, 340 newly diagnosed treatment-naïve patients fulfilling the 2022 ACR/EULAR classification criteria were included. Patients were stratified into tertiles according to pretreatment NLR. Baseline characteristics, temporal outcomes, and survival were compared. Infection-related mortality was further evaluated after stabilised inverse probability weighting (IPW).

Results: Higher pretreatment NLR was associated with greater disease severity, including higher Birmingham Vasculitis Activity Score ( P < 0.001) and Five-Factor Score ( P = 0.03), more frequent diffuse alveolar haemorrhage ( P = 0.015), poorer renal function ( P = 0.003), and more intensive remission-induction therapy, including methylprednisolone pulse therapy and rituximab. In contrast, interstitial lung disease was more common in patients with lower NLR ( P = 0.001). Despite these baseline differences, disease activity, glucocorticoid tapering, and cumulative organ damage became comparable after treatment initiation. Pretreatment NLR was not associated with relapse-free survival ( P = 0.44) but was associated with poorer overall survival ( P = 0.012) and higher infection-related mortality ( P = 0.002). After adjustment using IPW, the association with overall survival was no longer statistically significant, whereas the increased risk of infection-related mortality remained significant (HR 3.47, 95% CI 1.32–9.09, P = 0.034).

Conclusion: Pretreatment NLR reflected distinct inflammatory phenotypes and was independently associated with infection-related mortality in patients with newly diagnosed MPA. As an inexpensive and widely available marker, pretreatment NLR may have potential as a prognostic biomarker, although further validation is required to establish its clinical utility.

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Cite

BibTeXRIS
BibTeX
@article{hatta2026pretreatment,
  title = {{Pretreatment neutrophil-to-lymphocyte ratio is associated with clinical phenotypes and infection-related mortality in microscopic polyangiitis: the multicentre REVEAL cohort study}},
  author = {Muneyuki Hatta and Ryu Watanabe and Mayu Shiomi and Yuichi Masuda and Ayana Okazaki and Shogo Matsuda and Takuya Kotani and Tomoki Taniguchi and Shingo Iwasaka and Keiichiro Kadoba and Atsushi Manabe and Kaho Jo and Youhei Fujiki and Hirofumi Miyake and Hideki Oka and Shuji Sumitomo and Wataru Yamamoto and Shinya Nakatani and Akihiro Tsuda and Tetsuya Watanabe and Kazuhisa Asai and Motomu Hashimoto},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1948318},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1948318/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Pretreatment neutrophil-to-lymphocyte ratio is associated with clinical phenotypes and infection-related mortality in microscopic polyangiitis: the multicentre REVEAL cohort study
AU  - Muneyuki Hatta
AU  - Ryu Watanabe
AU  - Mayu Shiomi
AU  - Yuichi Masuda
AU  - Ayana Okazaki
AU  - Shogo Matsuda
AU  - Takuya Kotani
AU  - Tomoki Taniguchi
AU  - Shingo Iwasaka
AU  - Keiichiro Kadoba
AU  - Atsushi Manabe
AU  - Kaho Jo
AU  - Youhei Fujiki
AU  - Hirofumi Miyake
AU  - Hideki Oka
AU  - Shuji Sumitomo
AU  - Wataru Yamamoto
AU  - Shinya Nakatani
AU  - Akihiro Tsuda
AU  - Tetsuya Watanabe
AU  - Kazuhisa Asai
AU  - Motomu Hashimoto
PY  - 2026
DA  - 2026/10/19
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1948318
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1948318/full
AB  - Background: Microscopic polyangiitis (MPA) remains associated with substantial early mortality despite advances in immunosuppressive therapy, highlighting the need for simple biomarkers that facilitate LR) has been associated with disease activity and prognosis in antineutrophil cytoplasmic antibody-associated vasculitis (AAV), its phenotype-specific significance in newly diagnosed MPA remains unclear. We investigated whether pretreatment NLR is associated with clinical phenotype, disease course, and long-term outcomes in MPA.  Methods: Among 418 patients with MPA enrolled in the multicentre REVEAL cohort between 2005 and 2025, 340 newly diagnosed treatment-naïve patients fulfilling the 2022 ACR/EULAR classification criteria were included. Patients were stratified into tertiles according to pretreatment NLR. Baseline characteristics, temporal outcomes, and survival were compared. Infection-related mortality was further evaluated after stabilised inverse probability weighting (IPW).  Results: Higher pretreatment NLR was associated with greater disease severity, including higher Birmingham Vasculitis Activity Score ( P < 0.001) and Five-Factor Score ( P = 0.03), more frequent diffuse alveolar haemorrhage ( P = 0.015), poorer renal function ( P = 0.003), and more intensive remission-induction therapy, including methylprednisolone pulse therapy and rituximab. In contrast, interstitial lung disease was more common in patients with lower NLR ( P = 0.001). Despite these baseline differences, disease activity, glucocorticoid tapering, and cumulative organ damage became comparable after treatment initiation. Pretreatment NLR was not associated with relapse-free survival ( P = 0.44) but was associated with poorer overall survival ( P = 0.012) and higher infection-related mortality ( P = 0.002). After adjustment using IPW, the association with overall survival was no longer statistically significant, whereas the increased risk of infection-related mortality remained significant (HR 3.47, 95% CI 1.32–9.09, P = 0.034).  Conclusion: Pretreatment NLR reflected distinct inflammatory phenotypes and was independently associated with infection-related mortality in patients with newly diagnosed MPA. As an inexpensive and widely available marker, pretreatment NLR may have potential as a prognostic biomarker, although further validation is required to establish its clinical utility.
SN  - 1664-3224
ER  -