Monocyte Chemotactic Protein-1 (MCP-1): High Neonatal Levels May Represent an Early Marker of Autism

Monocyte Chemotactic Protein-1
Monocyte Chemotactic Protein-1  – Autism

A study published in the Journal of Neuroinflammation indicates that the chemokine monocyte chemotactic protein-1 (MCP-1) may represent an early marker for ASD.

Immune dysregulation, dysfunctional immune profiles involving inflammatory changes in the CNS and markers of inflammation have been associated with Autism Spectrum Disorder (ASD).

For example, increased levels of inflammatory cytokine transforming growth factor beta 1 (TGFβ1), chemokine macrophage chemoattractant CCL2, and CXCL8 were found in the brains of individuals with ASD. In addition to the elevated neuroinflammatory response in the autistic brain, altered levels of circulating cytokines and chemokine have also been reported.

Also, higher levels of macrophage migration inhibitory factor (MIF) and CXCL8 were observed in plasma and cerebrospinal fluid (CSF) specimens from individuals with ASD compared with those from typically developing (TD) controls and subjects with other developmental disabilities.

In addition, elevated plasma CCL5 and CCL2 were observed in ASD, whereas increased CCL2 found newborn bloodspot specimens have been shown to be related to the risk of ASD. Similarly, altered levels of TGFβ1 have also been found in plasma and serum specimens of ASD compared with TD controls.

Increased plasma levels of MIF have been correlated with more severe social impairment and decreased imaginative play, whereas lower TGFβ1 levels have been associated with more stereotypy, irritability, hyperactivity, and other behavioral symptoms and fewer adaptive behaviors. Significant associations between increased plasma levels of CCL5 and CXCL8 and more frequent aberrant behaviors and fewer adaptive behaviors have also been found.

Yet, most of the prior studies have used specimens taken after clinical diagnosis, and even with the relatively high prevalence, currently there are no definitive predictive or diagnostic markers for ASD.

As discussed in our previous news report, cortisol variation, IL-6 and TNF-α were recently suggested as potential biomarkers for ASD.

The monocyte chemoattractant protein-1 (MCP-1/CCL2) is a member of the C-C chemokine family, and a potent chemotactic factor for monocytes. MCP-1 is believed to be identical to JE, a gene whose expression is induced in mouse fibroblasts by platelet-derived growth factor. However, the human homolog that has been best characterized as CCL2 was first purified from human cell lines on the basis of its monocyte chemoattractant properties.

CCL2 is the first discovered human CC chemokine. Located on chromosome 17 (chr.17, q11.2), human MCP-1 is composed of 76 amino acids and is 13 kDa in size. MCP belongs to a family composed of at least four members (MCP-1, −2, −3, and −4). The sequence homology between CCL2 and other family members is high and varies between 61% for CCL8 and CCL4, and 71% for CCL7.

In the Journal of Neuroinflammation study Ousseny Zerbo and colleagues from Kaiser Permanente Northern California and the University of California at Davis, CA measured cytokine and chemokine concentrations in archived neonatal blood specimens maintained by the California Department of Public Health, and from the Early Markers for Autism (EMA) population-based, nested case-control study. Newborn blood specimens were obtained by the heel-stick method, usually within 24 to 48 hours of birth.

The researchers found elevated levels of MCP-1 and decreased levels of RANTES in the newborn blood of children subsequently diagnosed with autism.

This appears to be substantiated by a recent study using amniotic fluid and reporting elevated levels of MCP-1 for children who were later diagnosed with autism.

Interestingly, MCP-1 has been implicated in neuroinflammation related to diseases characterized by neuronal degeneration. In addition, it appears to contribute to brain development and heterologous desensitization, and to influence neurotransmitter systems and pathways such as opioids, cannabinoids, etc.

Thus, if replicated in future studies, these observations may indicate that cytokine/chemokine profiling and immune system’s assessment in the first few days of life may help in the early identification of particular neurodevelopmental trajectories.

Source: J Neuroinflammation, 2014, 11:113. doi: 10.1186/1742-2094-11-113.
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