Neutrophil-Lymphocyte Ratio (NLR) and Platelet-Lymphocyte Ratio (PLR) as neuroinflammatory biomarkers in Amyotrophic Lateral Sclerosis (ALS) progression

Authors

DOI:

https://doi.org/10.33448/rsd-v11i5.28073

Keywords:

Neurogenic inflammation; Neurodegeneration; Clinical rating; Prognosis.

Abstract

Amyotrophic Lateral Sclerosis (ALS) is a rapidly progressing multisystemic and multifactorial neurodegenerative disease that affects upper and lower motor neurons. Neuroinflammation is an important factor in neurodegeneration, the increase of immune cells in the neural tissue and degranulation of these cells causes neuronal damage and death, thus playing an important role in ALS pathophysiology. Studies have sought to use the neutrophil-lymphocyte ratio (NLR) and the platelet-lymphocyte ratio (PLR) as biomarkers of the inflammatory response indicative of diagnosis, stratification, progression and response to treatment of several diseases, including neurodegenerative. Thus, the aim of this study was to evaluate NLR and PLR as possible biomarkers in the neurodegenerative process. This retrospective cross-sectional study was carried out with 43 ALS patients selected at the Dr. Henrique Santillo Rehabilitation and Readaptation Center (CRER), Goiânia, Goiás – Brazil. Neutrophil, platelet, and lymphocyte counts were collected from the patient's most recent hemogram. Statistical analysis was performed using SPSS software, version 26. The correlation between NLR and PLR according to clinical condition showed a significant difference in these parameters during the initial phase of ALS development (p=0.01), revealing a marked inflammatory, with subsequent decline as the disease progresses (p=0.06). Furthermore, the results indicated a moderate positive linear relationship between the two variables (r=0.57; p<0.001), showing a joint increase in these parameters. Therefore, NLR and PLR are important indicators of inflammation and can be useful due to their simplicity, high reproducibility and low-cost for routine use.

References

Acharya, A. B., Shetty, I. P., Jain, S., Padakannaya, I., Acharya, S., Shettar, L., & Thakur, S. (2019). Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in chronic periodontitis before and after nonsurgical therapy. J Indian Soc Periodontol., 23(5), 419-423.

Akil, E., Bulut, A., Kaplan, I., Ozdemir, H. H., Arslan, D., & Aluclu, M. U. (2015). The increase of carcinoembryonic antigen (CEA), high-sensitivity C-reactive protein, and neutrophil/lymphocyte ratio in Parkinson’s disease. Neurol. Sci., 36(3), 423–428.

Arslan, B., Gürkan, O., Çetin, B., Arslan, Ö. A., Göv, T., Yazıcı, G., Eroglu, T., Avci, M. A., & Ozdemir, E. (2018). Evaluation of ABO blood groups and blood-based biomarkers as a predictor of growth kinetics of renal angiomyolipoma. Int. Urol. Nephrol., 50(12), 2131–2137.

Beers, D. R., & Appel, S. H. (2019). Immune dysregulation in amyotrophic lateral sclerosis: mechanisms and emerging therapies. Lancet Neurol., 18(2), 211–220.

Beers, D. R., Henkel, J. S., Zhao, W., Wang, J., Huang, A., Wen, S., Liao, B., & Appel, S. H. (2011). Endogenous regulatory T lymphocytes ameliorate amyotrophic lateral sclerosis in mice and correlate with disease progression in patients with amyotrophic lateral sclerosis. Brain, 134(5), 1293-1314.

Beers, D. R., Zhao, W., Wang, J., Zhang, X., Wen, S., Neal, D., Thonhoff, J. R., Alsuliman, A. S., Shpall, E. J., Rezvani, K., & Appel, S. H. (2017). ALS patients’ regulatory T lymphocytes are dysfunctional, and correlate with disease progression rate and severity. JCI Insight, 2(5), e89530.

Bilen, M. A., Martini, D. J., Liu, Y., Lewis, C., Collins, H. H., Shabto, J. M., Akce, M., Kissick, H. T., Carthon, B. C., Shaib, W. L., Alese, O. B., Pillai, R. N., Steuer, C. E., Wu, C. S., Lawson, D. H., Kudchadkar, R. R., El-Rayes, B. F., Master, V. A., Ramalingam, S. S.,… Harvey, R. D. (2019). The prognostic and predictive impact of inflammatory biomarkers in patients who have advanced-stage cancer treated with immunotherapy. Cancer, 125(1), 127–134.

Brown, R. H., & Al-Chalabi, A. (2017). Amyotrophic Lateral Sclerosis. N. Engl. J. Med., 377(2), 162–172.

Choi, S.-J., Hong, Y.-H., Kim, S.-M., Shin, J.-Y., Suh, Y. J., & Sung, J.-J. (2020). High neutrophil-to-lymphocyte ratio predicts short survival duration in amyotrophic lateral sclerosis. Sci Rep., 10(1), 428.

Dong, X., Nao, J., Shi, J., & Zheng, D. (2019). Predictive value of routine peripheral blood biomarkers in Alzheimer’s Disease. Front. Aging Neurosci., 11, 332.

Ferraiuolo, L., Kirby, J., Grierson, A. J., Sendtner, M., & Shaw, P. J. (2011). Molecular pathways of motor neuron injury in amyotrophic lateral sclerosis. Nat. Rev. Neurol., 7(11), 616–630.

Garbuzova-Davis, S., & Sanberg, P. R. (2014). Blood-CNS Barrier Impairment in ALS patients versus an animal model. Front. Cell Neurosci., 8, 21.

Gasparyan, A. Y., Ayvazyan, L., Mukanova, U., Yessirkepov, M., & Kitas, G. D. (2019). The platelet-to-lymphocyte ratio as an inflammatory marker in rheumatic diseases. Ann. Lab. Med., 39(4), 345–357.

Grollemund, V., Pradat, P. F., Querin, G., Delbot, F., Le Chat, G., Pradat-Peyre, J. F., & Bede, P. (2019). Machine Learning in Amyotrophic Lateral Sclerosis: Achievements, Pitfalls, and Future Directions. Front. Neurosci., 13, 1–28.

Harlan, B. A., Pehar, M., Killoy, K. M., & Vargas, M. R. (2019). Enhanced SIRT6 activity abrogates the neurotoxic phenotype of astrocytes expressing ALS-linked mutant SOD1. FASEB J., 33(6), 7084-7091.

Kalelioglu, T., Yuruyen, M., Gultekin, G., Yavuzer, H., Özturk, Y., Kurt, M., Topcu, Y., Doventas, A., & Emul, M. (2017). Neutrophil and platelet to lymphocyte ratios in people with subjective, mild cognitive impairment and early Alzheimer’s disease. Psychogeriatrics, 17(6), 506–508.

Kurimoto, T., Yin, Y., Habboub, G., Gilbert, H. Y., Li, Y., Nakao, S., Moghadam, A. H., & Benowitz, L. I. (2013). Neutrophils express oncomodulin and promote optic nerve regeneration. J. Neurosci., 33(37), 14816–14824.

Leone, M. A., Mandrioli, J., Russo, S., Cucovici, A., Gianferrari, G., Lisnic, V., Muresanu, D. F., Giuliani, F., Copetti, M., The Pooled Resource Open-Access ALS Clinical Trials Consortium, & Fontana, A. (2022). Neutrophils-to-Lymphocyte Ratio Is Associated with Progression and Overall Survival in Amyotrophic Lateral Sclerosis. Biomedicines, 10(2), 354.

Li, J., Chen, Q., Luo, X., Hong, J., Pan, K., Lin, X., Liu, X., Zhou, L., Wang, H., Xu, Y., Li, H., & Duan, C. (2015). Neutrophil-to-Lymphocyte Ratio Positively Correlates to Age in Healthy Population. J. Clin. Lab. Anal, 29(6), 437–443.

Marin, B., Boumédiene, F., Logroscino, G., Couratier, P., Babron, M. C., Leutenegger, A. L., Copetti, M., Preux, P. M., & Beghi, E. (2017). Variation in worldwide incidence of amyotrophic lateral sclerosis: a meta-analysis. Int. J. Epidemiol., 46(1), 57–74.

McCombe, A. P., & Henderson, D. R. (2011). The Role of Immune and Inflammatory Mechanisms in ALS. Curr. Mol. Med., 11(3), 246-254.

Murdock, B. J., Zhou, T., Kashlan, S. R., Little, R. J., Goutman, S. A., & Feldman, E. L. (2017). Correlation of Peripheral Immunity With Rapid Amyotrophic Lateral Sclerosis Progression. JAMA Neurol., 74(12), 1446–1454.

Najjar, M., Agrawal, S., Emond, J., & Halazun, K. (2018). Pretreatment neutrophil–lymphocyte ratio: useful prognostic biomarker in hepatocellular carcinoma. J. Hepatocell. Carcinoma, 5, 17–28.

Nam, K. W., Kwon, H. M., Jeong, H. Y., Park, J. H., Kim, S. H., & Jeong, S. M. (2018). High neutrophil to lymphocyte ratios predict intracranial atherosclerosis in a healthy population. Atherosclerosis, 269, 117–121.

Niazi, S., Nielsen, M. K., Sørensen, T. L., & Subhi, Y. (2019). Neutrophil-to-lymphocyte ratio in age-related macular degeneration: a systematic review and meta-analysis. Acta Ophthalmol., 97(6), 558-566.

Petrone, A. B., Eisenman, R. D., Steele, K. N., Mosmiller, L. T., Urhie, O., & Zdilla, M. J. (2019). Temporal dynamics of peripheral neutrophil and lymphocytes following acute ischemic stroke. Neurol. Sci., 40(9), 1877–1885.

Prado, L. G. R., Rocha, N. P., Souza, L. C., Bicalho, I. C. S., Gomez, R. S., Vidigal-Lopes, M., Braz, N. F. T., Vieira, E. L. M., & Teixeira, A. L. (2018a). Longitudinal assessment of clinical and inflammatory markers in patients with amyotrophic lateral sclerosis. J. Neurol. Sci., 394, 69–74.

Prado, L. G. R., Vieira, E. L. M., Rocha, N. P., Prado, V. G. R., Souza, L. C., & Teixeira, A. L. (2018b). Neuroinflamação na esclerose lateral amiotrófica. Rev. Bras. Neurol., 54(3), 22–27.

Rembach, A., Watt, A. D., Wilson, W. J., Rainey-Smith, S., Ellis, K. A., Rowe, C. C., Villemagne, V. L., Macaulay, S. L., Bush, A. I., Martins, R. N., Ames, D., Masters, C. L., Doecke, J. D., & AIBL Research Group. (2014). An increased neutrophil-lymphocyte ratio in Alzheimer’s disease is a function of age and is weakly correlated with neocortical amyloid accumulation. J. Neuroimmunol., 273(1-2), 65–71.

Robelin, L., & Aguilar, J. L. G. (2014). Blood Biomarkers for Amyotrophic Lateral Sclerosis: Myth or Reality? Biomed Res Int., 2014, e525097.

Ryberg, H., & Bowser, R. (2008). Protein biomarkers for amyotrophic lateral sclerosis. Expert Review of Proteomics, 5(2), 249–262.

Sargin, G., Senturk, T., Yavasoglu, I., & Kose, R. (2018). Relationship between neutrophil-lymphocyte, platelet-lymphocyte ratio and disease activity in rheumatoid arthritis treated with rituximab. Int. J. Rheum. Dis., 21(12), 2122–2127.

Scilla, K. A., Bentzen, S. M., Lam, V. K., Mohindra, P., Nichols, E. M., Vyfhuis, M. A., Bhooshan, N., Feigenberg, S. J., Edelman, M. J., & Feliciano, J. L. (2017). Neutrophil-lymphocyte ratio is a prognostic marker in patients with locally advanced (stage IIIA and IIIB) non-small cell lung cancer treated with combined modality therapy. Oncologist, 22(6), 737-742.

Spiller, K. J., Restrepo, C. R., Khan, T., Dominique, M. A., Fang, T. C., Canter, R. G., Roberts, C. J., Miller, K. R., Ransohoff, R. M., Trojanowski, J. Q., & Lee, V. M. Y. (2018). Microglia-mediated recovery from ALS-relevant motor neuron degeneration in a mouse model of TDP-43 proteinopathy. Nat. Neurosci., 21(3), 329–340.

Su, F. C., Goutman, S. A., Chernyak, S., Mukherjee, B., Callaghan, B. C., , Batterman, S., & Feldman, E. L. (2016). Association of Environmental Toxins With Amyotrophic Lateral Sclerosis. JAMA Neurol., 73(7), 803-811.

Thomas, M. R., & Storey, R. F. (2015). The role of platelets in inflammation. Thromb Haemost., 114(3), 449–458.

Tokgoz, S., Kayrak, M., Akpinar, Z., Seyithanoǧlu, A., Güney, F., & Yürüten, B. (2013). Neutrophil lymphocyte ratio as a predictor of stroke. J. Stroke Cerebrovasc. Dis., 22(7), 1169–1174.

Turner, M. R., Kiernan, M. C., Leigh, P. N., & Talbot, K. (2009). Biomarkers in amyotrophic lateral sclerosis. The Lancet Neurology, 8(1), 94–109.

Wei, Q. Q., Hou, Y. B., Zhang, L.Y., Ou, R.W., Cao, B., Chen, Y. P., & Shang, H. F. (2022). Neutrophil-to-lymphocyte ratio in sporadic amyotrophic lateral sclerosis. Neural Regen Res, 17(4), 875-880.

Yang, Q. Q., & Zhou, J. W. (2019). Neuroinflammation in the central nervous system: Symphony of glial cells. Glia, 67(6), 1017–1035.

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Published

07/04/2022

How to Cite

SANTOS, K. de F. .; AZEVEDO, R. M. .; COSTA, C. C. P. da .; BENTO, D. da C. P. .; REIS, A. A. da S. .; SANTOS, R. da S. . Neutrophil-Lymphocyte Ratio (NLR) and Platelet-Lymphocyte Ratio (PLR) as neuroinflammatory biomarkers in Amyotrophic Lateral Sclerosis (ALS) progression. Research, Society and Development, [S. l.], v. 11, n. 5, p. e29611528073, 2022. DOI: 10.33448/rsd-v11i5.28073. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/28073. Acesso em: 26 dec. 2024.

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Health Sciences