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Severity and patterns of blood-nerve barrier breakdown in patients with chronic inflammatory demyelinating polyradiculoneuropathy: correlations with clinical subtypes.

Shimizu F, Sawai S, Sano Y, Beppu M, Misawa S, Nishihara H, Koga M, Kuwabara S, Kanda T - PLoS ONE (2014)

Bottom Line: Furthermore, the severity of BNB disruption after exposure to the sera was associated with higher Hughes grade, lower MRC score, more pronounced slowing of motor nerve conduction in the median nerve and higher frequency of abnormal temporal dispersion.The extent of BNB disruption in the setting of CIDP is associated with clinical disability and demyelination in the nerve trunk.These observations may explain the phenotypical differences between CIDP subtypes.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, Ube, Japan.

ABSTRACT

Objective: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is currently classified into clinical subtypes, including typical and atypical forms (multifocal acquired demyelinating sensory and motor neuropathy (MADSAM) and distal acquired demyelinating symmetric neuropathy (DADS)). The aim of this study was to elucidate the patterns and severity of breakdown of the blood-nerve barrier (BNB) in each CIDP subtype.

Methods: We evaluated the effects of sera obtained from patients with typical CIDP, MADSAM and DADS and control subjects on the expression levels of tight junction proteins and transendothelial electrical resistance (TEER) value in human peripheral nerve microvascular endothelial cells (PnMECs).

Results: The sera obtained from the patients with the three clinical phenotypes of CIDP decreased the amount of claudin-5 protein levels and TEER values in the PnMECs. In addition, the sera obtained from typical CIDP patients more prominently reduced claudin-5 protein levels and TEER values in the PnMECs than did that obtained from the MADSAM and DADS patients. Furthermore, the severity of BNB disruption after exposure to the sera was associated with higher Hughes grade, lower MRC score, more pronounced slowing of motor nerve conduction in the median nerve and higher frequency of abnormal temporal dispersion.

Conclusions: Sera derived from typical CIDP patients destroy the BNB more severely than those from MADSAM or DADS patients. The extent of BNB disruption in the setting of CIDP is associated with clinical disability and demyelination in the nerve trunk. These observations may explain the phenotypical differences between CIDP subtypes.

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Associations between the clinical findings and BNB malfunction in the patients with CIDP.Correlations between the claudin-5 to actin protein ratios and the TEER values in the FH-BNBs following exposure to sera and the clinical parameters in the patients with CIDP. Associations between the claudin-5 to actin protein ratios and TEER values and the Hughes grade (A), duration of disease from onset (B), total Medical Research Council (MRC) scores for four muscle groups (deltoid, wrist extensor, iliopsoas, and tibialis anterior muscles) (C), MRC score for the iliopsoas muscle (D) and response to treatment, including intravenous immunoglobulin (IVIg) and corticosteroids (E). A lower ratio of claudin-5 to actin proteins was significantly associated with a higher Hughes grade, while a lower TEER value significantly correlated with a higher Hughes grade and lower MRC score.
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pone-0104205-g002: Associations between the clinical findings and BNB malfunction in the patients with CIDP.Correlations between the claudin-5 to actin protein ratios and the TEER values in the FH-BNBs following exposure to sera and the clinical parameters in the patients with CIDP. Associations between the claudin-5 to actin protein ratios and TEER values and the Hughes grade (A), duration of disease from onset (B), total Medical Research Council (MRC) scores for four muscle groups (deltoid, wrist extensor, iliopsoas, and tibialis anterior muscles) (C), MRC score for the iliopsoas muscle (D) and response to treatment, including intravenous immunoglobulin (IVIg) and corticosteroids (E). A lower ratio of claudin-5 to actin proteins was significantly associated with a higher Hughes grade, while a lower TEER value significantly correlated with a higher Hughes grade and lower MRC score.

Mentions: We next examined the associations between the clinical, laboratory and electrophysiological findings and the ratio of claudin-5 to actin proteins and/or the TEER values in the FH-BNBs exposed to the sera from the CIDP patients. Consequently, the decrease in either the claudin-5 protein level or TEER value in the FH-BNBs was found to be associated with the clinical severity. In addition, a lower ratio of claudin-5 to actin proteins significantly correlated with a higher Hughes grade (Fig. 2A) and higher Q Alb level (Fig. 3C), while a lower TEER value was significantly associated with a higher Hughes grade (Fig. 2A), lower MRC score (Fig. 2C), particularly in the iliopsoas muscle (Fig. 2D), more pronounced slowing of the motor nerve conduction in the median nerve (Fig. 4B) and higher frequency of abnormal temporal dispersion (Fig. 4F). In contrast, no significant differences were noted between the claudin-5 to actin protein ratio or TEER value and the duration of disease from onset (Fig. 2B), response to immunotherapy (Fig. 2E), concentration of CSF proteins (Fig. 3A), IgG index (Fig. 3B), distal latency (Fig. 4A), conduction block (Fig. 4E) or CMAP amplitude (Fig. 4C) or TLI index (Fig. 4D) in the median nerve.


Severity and patterns of blood-nerve barrier breakdown in patients with chronic inflammatory demyelinating polyradiculoneuropathy: correlations with clinical subtypes.

Shimizu F, Sawai S, Sano Y, Beppu M, Misawa S, Nishihara H, Koga M, Kuwabara S, Kanda T - PLoS ONE (2014)

Associations between the clinical findings and BNB malfunction in the patients with CIDP.Correlations between the claudin-5 to actin protein ratios and the TEER values in the FH-BNBs following exposure to sera and the clinical parameters in the patients with CIDP. Associations between the claudin-5 to actin protein ratios and TEER values and the Hughes grade (A), duration of disease from onset (B), total Medical Research Council (MRC) scores for four muscle groups (deltoid, wrist extensor, iliopsoas, and tibialis anterior muscles) (C), MRC score for the iliopsoas muscle (D) and response to treatment, including intravenous immunoglobulin (IVIg) and corticosteroids (E). A lower ratio of claudin-5 to actin proteins was significantly associated with a higher Hughes grade, while a lower TEER value significantly correlated with a higher Hughes grade and lower MRC score.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4126720&req=5

pone-0104205-g002: Associations between the clinical findings and BNB malfunction in the patients with CIDP.Correlations between the claudin-5 to actin protein ratios and the TEER values in the FH-BNBs following exposure to sera and the clinical parameters in the patients with CIDP. Associations between the claudin-5 to actin protein ratios and TEER values and the Hughes grade (A), duration of disease from onset (B), total Medical Research Council (MRC) scores for four muscle groups (deltoid, wrist extensor, iliopsoas, and tibialis anterior muscles) (C), MRC score for the iliopsoas muscle (D) and response to treatment, including intravenous immunoglobulin (IVIg) and corticosteroids (E). A lower ratio of claudin-5 to actin proteins was significantly associated with a higher Hughes grade, while a lower TEER value significantly correlated with a higher Hughes grade and lower MRC score.
Mentions: We next examined the associations between the clinical, laboratory and electrophysiological findings and the ratio of claudin-5 to actin proteins and/or the TEER values in the FH-BNBs exposed to the sera from the CIDP patients. Consequently, the decrease in either the claudin-5 protein level or TEER value in the FH-BNBs was found to be associated with the clinical severity. In addition, a lower ratio of claudin-5 to actin proteins significantly correlated with a higher Hughes grade (Fig. 2A) and higher Q Alb level (Fig. 3C), while a lower TEER value was significantly associated with a higher Hughes grade (Fig. 2A), lower MRC score (Fig. 2C), particularly in the iliopsoas muscle (Fig. 2D), more pronounced slowing of the motor nerve conduction in the median nerve (Fig. 4B) and higher frequency of abnormal temporal dispersion (Fig. 4F). In contrast, no significant differences were noted between the claudin-5 to actin protein ratio or TEER value and the duration of disease from onset (Fig. 2B), response to immunotherapy (Fig. 2E), concentration of CSF proteins (Fig. 3A), IgG index (Fig. 3B), distal latency (Fig. 4A), conduction block (Fig. 4E) or CMAP amplitude (Fig. 4C) or TLI index (Fig. 4D) in the median nerve.

Bottom Line: Furthermore, the severity of BNB disruption after exposure to the sera was associated with higher Hughes grade, lower MRC score, more pronounced slowing of motor nerve conduction in the median nerve and higher frequency of abnormal temporal dispersion.The extent of BNB disruption in the setting of CIDP is associated with clinical disability and demyelination in the nerve trunk.These observations may explain the phenotypical differences between CIDP subtypes.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, Ube, Japan.

ABSTRACT

Objective: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is currently classified into clinical subtypes, including typical and atypical forms (multifocal acquired demyelinating sensory and motor neuropathy (MADSAM) and distal acquired demyelinating symmetric neuropathy (DADS)). The aim of this study was to elucidate the patterns and severity of breakdown of the blood-nerve barrier (BNB) in each CIDP subtype.

Methods: We evaluated the effects of sera obtained from patients with typical CIDP, MADSAM and DADS and control subjects on the expression levels of tight junction proteins and transendothelial electrical resistance (TEER) value in human peripheral nerve microvascular endothelial cells (PnMECs).

Results: The sera obtained from the patients with the three clinical phenotypes of CIDP decreased the amount of claudin-5 protein levels and TEER values in the PnMECs. In addition, the sera obtained from typical CIDP patients more prominently reduced claudin-5 protein levels and TEER values in the PnMECs than did that obtained from the MADSAM and DADS patients. Furthermore, the severity of BNB disruption after exposure to the sera was associated with higher Hughes grade, lower MRC score, more pronounced slowing of motor nerve conduction in the median nerve and higher frequency of abnormal temporal dispersion.

Conclusions: Sera derived from typical CIDP patients destroy the BNB more severely than those from MADSAM or DADS patients. The extent of BNB disruption in the setting of CIDP is associated with clinical disability and demyelination in the nerve trunk. These observations may explain the phenotypical differences between CIDP subtypes.

Show MeSH
Related in: MedlinePlus