Table 1.
Figure 1.
The sera obtained from the patients with t-CIDP, MADSAM and DADS disrupted the BNB.
(A) – (D) Effects of the sera obtained from patients with three different phenotypes of chronic inflammatory demyelinating polyneuropathy (CIDP) on the protein levels of claudin-5 and occludin in the FH-BNBs, as determined using a Western blot analysis. The cells were exposed to sera from either patients with typical CIDP (t-CIDP) (A), multifocal acquired demyelinating sensory and motor neuropathy (MADSAM) (B) or distal acquired demyelinating symmetric neuropathy (DADS) (C) or healthy volunteers (D). (E) The sera obtained from the patients with t-CIDP, MADSAM neuropathy and DADS neuropathy decreased the protein ratio of claudin-5 to actin proteins in the FH-BNBs compared to that observed following exposure to the sera from the healthy volunteers. The decrease in the claudin-5 levels in the FH-BNBs was greater after incubation with the sera obtained from the t-CIDP patients than after that with the sera from the patients with MADSAM and DADS. (F) There were no significant differences between the patients with the three different phenotypes of CIDP and the healthy controls regarding the occludin protein levels in the FH-BNBs. (G) The effects of the sera on the transendothelial electrical resistance (TEER) values in the FH-BNBs were also evaluated. Adding sera obtained from the patients with t-CIDP, MADSAM neuropathy or DADS neuropathy resulted in decreased TEER values in the FH-BNBs in comparison with that observed in the cells treated with the sera obtained from the healthy volunteers. Markedly decreased TEER values in FH-BNBs were also observed in the FH-BNBs following incubation with the sera obtained from the t-CIDP patients compared to that noted in the cells incubated with sera from patients with MADSAM or DADS neuropathy. The TEER values were decreased following exposure to the sera obtained from the patients with DADS neuropathy compared to that observed after exposure to the sera obtained from the patients with MADSAM neuropathy. The bars indicate the mean level in each group. Control: non-conditioned DMEM containing 20% FBS. t-CIDP: conditioned medium with 10% sera obtained from patients with t-CIDP diluted with non-conditioned DMEM containing 10% FBS. MADSAM: conditioned medium with 10% sera obtained from patients with MADSAM diluted with non-conditioned DMEM containing 10% FBS. DADS: conditioned medium with 10% sera obtained from patients with DADS diluted with non-conditioned DMEM containing 10% FBS. Normal: conditioned medium with 10% sera obtained from a healthy volunteer diluted with non-conditioned medium of DMEM containing 10% FBS.
Figure 2.
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.
Figure 3.
Associations between the CSF parameters and BNB disruption 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 cerebrospinal fluid (CSF) parameters, including the CSF protein level (A), IgG index (B) and albumin ratio (Q Alb) (C) in the patients with CIDP. A lower ratio of claudin-5 to actin proteins was significantly associated with a higher Q Alb.
Figure 4.
Correlation between the electrophysiological findings and BNB disruption in the patients with CIDP.
Associations between the claudin-5 to actin protein ratios and the TEER values in the FH-BNBs following exposure to sera and the electrophysiological findings of the median nerve, including the distal nerve latency (A), conduction velocity (B), compound muscle action potential (CMAP) (C), terminal latency index (TLI index) (D) and presence of conduction block (E) or abnormal temporal dispersion (F) in the patients with CIDP. A lower TEER value was highly associated with slower motor nerve conduction and the presence of abnormal temporal dispersion.