To Investigate The Clinical Characteristics Of Known Antibodies Negative Atypical IIDDs Based On TBA

Background:Idiopathic inflammatory demyelinating diseases(IIDDs)of the central nervous system(CNS)are a large group of autoimmune-related CNS idiopathic diseases characterized by inflammatory loss of myelin.According to the characteristics of clinical manifestations,imaging features,course and therapeutic response to commonly drugs for MS,IIDDs can be divided into typical IIDDs that is,MS and a large group of atypical IIDDs other than MS.New ways of classifying atypical IIDDs centered on pathogenic antibodies such as AQP4-IgG and MOG-IgG have been identified.However,the potential antigenic targets of known antibodies negative atypical IIDDs remain unclear.Tissue based assay(TBA)indirect immunofluorescence is an antibody detection method that is not limited by known antigens,and its clinical significance for detecting unknown antibodies of known antibodies negative atypical IIDDs needs to be deeply explored.Objectives:1.To investigate the sensitivity and specificity of TBA in detecting antibodies associated with IIDDs in the central nervous system.2.To investigate the presence of unknown specific antibodies against CNS myelin in patients with known antibodies negative atypical IIDDs using the TBA.3.To classify and summarize the clinical features of known antibodies negative atypical IIDDs based on detection of TBA.Methods:1.Cerebrospinal fluid(CSF)and serum samples were collected from patients with known antibodies positive atypical IIDDs that detected by CBA,as well as serum and CSF samples from patients with CNS diseases without specific antibody such as non-CNS inflammatory diseases and multiple sclerosis(MS).The antibody expression of those samples was detected by TBA.2.Record and compare the clinical characteristics of patients with atypical IIDDs known to be antibody-negative,AQP4-IgG-positive NMOSD,and MOGAD.3.Serum and CSF samples from patients with known antibodies negative atypical IIDDs are detected by TBA.Patients with known antibodies negative atypical IIDDs will be further classified based on the detection results of TBA and compare the differences of clinical characteristics between different subgroups.Results:1.Ten AQP4-IgG positive samples,6 GFAP-IgG positive samples,and 6 MOG-IgG positive samples were detected by CBA.The expression of the three antibodies was retested by TBA with rat brain tissue as the matrix,and their positive rates were 80%,83.3%,and 0%,respectively;4 AQP4-IgG positive samples,3 GFAP-IgG positive samples,and 5 MOGIgG positive samples were retested with monkey brain tissue,and their positive rates were 75%,66.7%,and 0%,respectively.Fifty-seven CNS non-inflammatory disease samples were detected by TBA with rat brain tissue,of which 44 samples were detected by monkey brain tissue,and the seroprevalences were 30.6%and 29.2%,respectively;the CSF positive rates were 76.2%and 23.8%,respectively,of which the positive rates of neuronal cell-associated antibodies were 66.7%and 4.8%,respectively.Thirty MS samples were examined by TBA with both rat brain tissue and monkey brain tissue,and the seroprevalences were 20.0%and 6.7%,respectively;the CSF positive rates were 73.3%and 33.3%,respectively,of which the neuronal cell-associated antibody positive rates were 60.0%and 6.7%,respectively.It is speculated that the neuronal cell-associated antibodies found in CSF by TBA using rat brain tissue as the matrix may be caused by species differences or antibodies produced secondary to nerve tissue destruction,which are non-pathogenic antibodies and should be considered negative.2.Patients in the known antibodies negative group accounted for 45.3%of atypical IIDDs included in the same period and the females of this group is 58.7%,with prominent brainstem and spinal cord symptoms and less optic nerve symptoms than the other two groups.Patients in the known antibodies negative group had a significantly lower proportion of cortical and subcortical lesions than those in the MOGAD group,while the proportion of lesions in the diencephalon was significantly lower than that in the AQP4-IgG-positive NMOSD group.3.The presence of unknown antibodies was determined in 81.2%of patients with known antibodies negative atypical IIDDs by TBA with rat brain tissue as a matrix.Neuronal cell-associated antibodies account for the vast majority of women,and the monophasic course of the disease is predominant,with localized spinal cord or brainstem symptoms common.The male to female ratio was similar in astrocyte-associated antibody group,commonly with non-monophasic course,and involvement of spinal cord,brainstem,optic nerve and brain was common.Conclusions:1.Neuronal cell-associated antibodies in CSF detected by TBA based on rat brain tissue should be considered negative.The positive rate of this method in detecting serum and cerebrospinal fluid samples from patients with known antibody-positive IIDDs is high,while the positive rate of samples from patients with CNS diseases without specific antibody findings is low,which can be tried to detect unknown antibodies to atypical IIDDs with known antibody-negative,and can guide clinical practice.2.Known antibodies negative atypical IIDDs account for a certain proportion in atypical IIDDs and deserve the attention of clinicians.The male to female ratio of patients in the antibody-negative group is similar,with prominent spinal cord and brainstem symptoms,but optic nerve and diencephalic lesions are rare.3.In most patients with atypical IIDDs who are known to be negative for antibodies,unknown antibodies against astrocytes can be detected by TBA.Neuronal cell-associated antibodies accounted for the vast majority of women,and the monophasic course of the disease was predominant,commonly with localized spinal cord or brainstem symptoms,significantly different from the astrocyte-associated antibody group.17 tables and 53 references...