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. 2025 May 1;64(5):3160-3165.
doi: 10.1093/rheumatology/keae606.

Neutrophil-to-lymphocyte ratio as a biomarker for clinical response after autologous haematopoietic stem cell transplantation in systemic sclerosis

Shiri Keret  1   2 , Lisa Kaly  1   2 , George Schett  3   4 , Christina Bergmann  3   4 , Erik Feldman  2 , Tsila Zuckerman  2   5 , Dana Yehudai-Ofir  2   5 , Aniela Shouval  1   2 , Abid Awisat  1   2 , Itzhak Rosner  1   2 , Michael Rozenbaum  1   2 , Nina Boulman  1   2 , Alaa Sawaed  1   2 , Emilia Hardak  6   2 , Jörg Henes  7 , Gleb Slobodin  1   2 , Doron Rimar  1   2
Affiliations

Neutrophil-to-lymphocyte ratio as a biomarker for clinical response after autologous haematopoietic stem cell transplantation in systemic sclerosis

Shiri Keret et al. Rheumatology (Oxford). .

Abstract

Objective: SSc is a complex disease that affects various target organs, making it difficult to assess response and determine remission or relapse. A baseline neutrophil-to-lymphocyte ratio (NLR) >2.95 is associated with severe progressive skin and lung disease and decreased 5-year survival in SSc. However, it is unknown whether NLR changes in response to treatment. To retrospectively evaluate NLR changes as a biomarker for treatment response in SSc.

Methods: Progressive diffuse SSc patients who were treated with autologous haematopoietic stem cell transplantation (AHSCT group), with combination therapy of rituximab and MMF (combination group) or chimeric antigen receptor-T-cell (CAR-T) therapy group, were recruited along with healthy controls (HC group). NLR, modified Rodnan Skin Score (mRSS) and forced vital capacity (FVC)% predicted were repeatedly assessed over 2 years.

Results: Fifteen patients were recruited in the AHSCT group, 15 in the combination group and 6 patients in the CAR-T group. Baseline mean NLR was high (>2.95) in AHSCT, combination groups and CAR-T compared with HC. All treatment arms showed a statistically significant decrease in mRSS values and an increase in FVC% at each time point up to 12 months. In a linear mixed model, NLR significantly decreased up to 24 months only in the AHSCT group. NLR correlated with mRSS and FVC exclusively in the AHSCT group. NLR increased above 3 in two patients who experienced a relapse after AHSCT.

Conclusion: NLR is a simple biomarker that correlated with outcome measures in SSc following AHSCT but not with conventional therapy or CAR-T therapy. It is suggested that a decrease in NLR following AHSCT may indicate remission, whereas an increase may be associated with exacerbation. Further research is needed to validate these novel findings.

Keywords: MMF; SSc; autologous haematopoietic stem cell transplantation; biomarker; neutrophils-to-lymphocytes ratio; rituximab.

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