Peripheral immunity relate to disease progression and prognosis in amyotrophic lateral sclerosis

Abstract

Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Abnormalities in the peripheral immune system in ALS have been paid attention; however, the results of changes in peripheral immune parameters were inconsistent. Methods: A total of 1109 ALS patients were enrolled in the study. All patients received clinical evaluation and peripheral immune parameters measurement. The outcomes were analyzed by correlation analysis, multiple linear regression and cox survival analysis. Results: We found that ALS patients had significantly higher percentage of CD4⁺ T cells (39.3 vs. 37.1%, p < 0.001) and CD4⁺/CD8⁺ ratio (1.88 vs. 1.72, p = 0.011), significantly lower IgG (11.73 vs.12.82, p < 0.001) and IgA (2130.70 vs. 2284.8, p = 0.013) compared with the health controls. In the multivariate linear model, we found that each increase of 1.262, 0.278, and 4.44E-4 in ALSFRS-R scores were significantly associated with each increment of lymphocyte count, IgG, and IgA, respectively. However, each decrease of 0.341, 0.068, and 0.682 in ALSFRS-R score was associated with each increment in neutrophils, CD4⁺ T cells, and CD4⁺/CD8⁺ ratio, respectively. Cox survival regression analysis showed that the death risk of ALS patients was related to the levels of C3 (HR 0.592, 95% CI 0.361–0.973). Conclusion: We found that there were differences in peripheral immune parameters of ALS patients with the severity of the disease, especially neutrophil, lymphocyte, CD4⁺ T, and IgG; C3 is an independent predictor of survival in ALS patients. More studies are needed to elucidate the mechanisms associated with altered immune parameters in ALS.

Keywords:

• Amyotrophic lateral sclerosis
• peripheral immunity
• disease progression
• prognosis

Acknowledgements

The authors thank all the participants of the study.

Authors’ contributions

QRJ searched and selected the studies, analyzed the data, drafted and revised the article. QQW, LYZ and TMY contributed to sample collection and gave suggestions on study design. JYL, YX, CYL, YBH, RWO, KCL, BZ and YW contributed to sample collection. XHL and HFS designed the study and gave suggestions on revising the article.

Availability of data and material

Anonymized data will be shared upon request with any qualified investigator.

Declaration of interest

The authors declare that they have no conflict of interest.

Ethical approval

This study was approved by the Ethics Committee of West China Hospital of Sichuan University, and all patients in the study signed informed consent before participating in the study (Approval No. 2015 (236)).

Informed consent

This article does not contain any previously unpublished studies that would require informed consent.

Additional information

Funding

This article was supported by the Sichuan Science and Technology Program (Grant No. 2022ZDZX0023), the National Natural Science Foundation of China (Grant No. 82101485), and Science and Technology commission foundation of Chengdu City (Grant No. 2021-YF05-00242-SN).