Neutrophil-related factors as biomarkers in EAE and MS

Abstract

Using a mouse model of multiple sclerosis (MS), the authors show that neutrophils expand in the bone marrow and accumulate in the circulation before clinical onset of disease. Early in disease development, neutrophils infiltrate the CNS, which is suppressed by G-CSF receptor deficiency and blockade of CXCL1 to ameliorate disease. In patients with MS, systemic expression of neutrophil-related mediators correlates with new lesion formation, lesion burden, and clinical disability.

Isolated adrenocorticotropic hormone deficiency possibly caused by nivolumab in a metastatic melanoma patient

“…3 In addition, CXCL5 is a biomarker of T-helper 17-mediated autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis and glomerulonephritis. 4 In our present case, the serum level of sCD163 and CXCL5 began to increase 6 weeks after the administration of nivolumab, suggesting the existence of autoimmune-like reaction. To our knowledge, there is no English-language report describing an idiopathic ACTH deficiency in nivolumab-treated patients except for hypophysitis cases that are not further classified 5 and may include idiopathic ACTH deficiency cases.…”

Kruppel-like factor 4 regulates neutrophil activation

“…9 Accumulating clinical and experimental evidence implicates neutrophils in the pathogenesis of MS and EAE. [11][12][13]26,27 Upon immunization, Cre mice developed EAE with disease onset at ;7 to 14 days and peak at ;21 to 28 days ( Figure 2D). In contrast, K4-cKO mice showed a delayed onset and significant reduction in severity of EAE despite 100% disease incidence ( Figure 2D; supplemental 7A).…”

“…10,11 Neutrophils in the blood of MS patients exhibit a primed phenotype, and both neutrophil number and biomarkers of neutrophil activity increase during relapses. 11 In EAE, neutrophils comprise a significant percentage of CNS-infiltrating leukocytes prior to disease onset and relapse, and disease was ameliorated when neutrophils were depleted prior to, but not after, disease onset or relapse, suggesting important neutrophil function during the initial formation of MS lesions. 12 It has been reported that neutrophils may play a role in mediating blood-brain barrier breakdown.…”

Preferential Recruitment of Neutrophils into the Cerebellum and Brainstem Contributes to the Atypical Experimental Autoimmune Encephalomyelitis Phenotype

“…In addition, neutrophil infiltration is prominent in early active demyelinating spinal cord (SC) lesions of neuromyelitis optica patients (17). Furthermore, a recent study demonstrated that systemic expression of neutrophil-associated factors, including CXCL1, CXCL5, and neutrophil elastase, correlated with measures of MS lesion burden and clinical disability (18), further supporting the involvement of neutrophils in neuroinflammatory diseases. MS is a heterogeneous disease in terms of inflammatory lesions (19,20).…”