The Role Of Btk/NF-?B Signaling Pathway And Related Cytokines In The Pathogenesis Of Optic Neuromyelitis Spectrum Disease

Objective:1.To understand the changes in the acute phase of NMOSD patients,the levels of Btk,NF-?B,PI3 K,Ikk and CXCL2 and CXCL12 mRNA in mononuclear cells(PBMCs)of NMOSD patients were detected,and to explore the correlation between the four indicators of Btk pathway and CXCL2 and CXCL12.Combined with EDSS score,the correlation between CXCL2 and CXCL12 mRNA and disease severity was explored.2.The levels of IL-6,CXCL2 and CXCL12 in peripheral blood serum of NMOSD patients were detected and compared with the healthy control group.The correlation between the above indicators and the severity of the disease was discussed in combination with EDSS score.3.To investigate the correlation between serum AQP4-Ab positivity,antibody level and the number of involved segments in spinal cord MRI in NMOSD patients.Methods:From January 2018 to January 2019,33 patients admitted to the department of neurology of the Second Hospital of Hebei Medical University in the acute phase of NMOSD were selected as the experimental group,and 33 healthy patients with matching gender and age were selected as the control group.EDSS score,spinal cord MRI and blood AQP4-Ab were measured in the enrolled NMOSD patients.The levels of Btk,NF-?B,PI3 K,Ikk,CXCL2 and CXCL12 in PBMCs were detected by PCR.The levels of IL-6,CXCL2 and CXCL12 in peripheral serum were detected by ELISA and compared with those in healthy subjects.Results:1.The levels of Btk,NF-?B,PI3 K,Ikk mRNA in the NMOSD group were significantly higher than those in the control group;2.CXCL2 mRNA and serum levels and in the NMOSD group were significantly higher than those in the control group,with statistically significant differences.CXCL12 mRNA and serum levels in the NMOSD group were significantly higher than those in the control group,with statistically significant differences.There was a significant positive correlation between the mRNA levels of Btk,NF-?B,PI3 K and Ikk and the mRNA levels of CXCL2 and CXCL12.CXCL2 mRNA level was positively correlated with EDSS score.There was no linear correlation between EDSS score and CXCL12 mRNA,CXCL2 and CXCL12 serum levels;3.Serum IL-6 level in the NMOSD group was similar to that in the control group,and the difference was not statistically significant;4.Compared with AQP4-Ab negative patients,AQP4-Ab positive patients in the acute phase of NMOSD had more spinal cord involvement segments,and the difference was statistically significant.There was no linear correlation between the titer of AQP4-Ab antibody and the number of spinal cord involved segments.Conclusion:1.The Btk/NF-?B signaling pathway may be involved in the pathogenesis of NMOSD;2.CXCL2 and CXCL12 may be involved in the inflammatory course of NMOSD and are associated with kinases in the Btk/NF-?B signaling pathway,suggesting that they are involved in signal transduction in this pathway;CXCL2 may be an observational factor for disease severity,which needs to be further validated;3.Whether serum IL-6 is involved in the pathogenesis of NMOSD still needs to be further verified;4.The number of spinal cord involved segments in the acute phase of NMOSD patients may be correlated with positive blood AQP4-Ab,and the titer does not predict the number of spinal cord involved segments.