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Correlation of peripheral immunity with rapid amyotrophic lateral sclerosis progression

JAMA Neurology Sep 28, 2017

Murdock BJ, et al. - This longitudinal cohort study was performed to evaluate peripheral inflammatory markers in participants with amyotrophic lateral sclerosis (ALS) and healthy control individuals. Furthermore, the authors aimed to track immune changes in ALS and ascertain whether these changes correlate with disease progression. They found that during ALS, changes occurred in the immune system and could contribute to the pathologic features of ALS.

Methods
  • From June 18, 2014, through May 26, 2016, the authors isolated leukocytes from peripheral blood samples from 35 controls and 119 participants with ALS at the ALS Clinic at the University of Michigan, Ann Arbor.
  • For this study, follow-up visits occurred every 6 to 12 months.
  • At multiple points, 51 participants with ALS provided samples.
  • They measured immune cell populations and compared between control and ALS groups.
  • They also evaluated surface marker expression of CD11b+ myeloid cells.
  • They correlated changes over time with disease progression using multivariate regression.

Results
  • The authors enrolled 35 controls (17 women [48.6%] and 18 men [51.4%]; mean [SD] age, 63.5 [9.9] years) and 119 participants with ALS (50 women [42.0%] and 69 men [68.0%]; mean [SD] age, 61.4 [11.5] years).
  • Participants with ALS had increased mean (SEM) counts ( × 106/mL) of total leukocytes (4.57 [0.29; 95% CI, 3.94-5.11] vs 5.53 [0.16; 95% CI, 5.21-5.84]), neutrophils (2.87 [0.23; 95% CI, 2.40-3.35] vs 3.80 [0.12; 95% CI, 3.56-4.04]), CD16+ monocytes (0.03 [0.003; 95% CI, 0.02-0.04] vs 0.04 [0.002; 95% CI, 0.03-0.04]), CD16- monocytes (0.25 [0.02; 95% CI, 0.21-0.30] vs 0.29 [0.01; 95% CI, 0.27-0.31]), and natural killer cells (0.13 [0.02; 95% CI, 0.10-0.17] vs 0.18 [0.01; 95% CI, 0.16-0.21]) compared with controls.
  • Furthermore, they observed an acute, transient increase in a population of CD11b+ myeloid cells expressing HLA-DR, CD11c, and CX3CR1.
  • At last, early changes in immune cell numbers had a significant relationship with disease progression measured by change in ALSFRS-R score, especially neutrophils (-4.37 [95% CI, -6.60 to -2.14] per 11.47 × 104/mL [SD, 58.04 × 104/mL] per year) and CD4 T cells (-30.47 [95% CI, -46.02 to -14.94] per -3.72 × 104/mL [SD, 26.21 × 104/mL] per year).
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