OCB-positive Group Research Articles

Characteristics of cerebrospinal fluid oligoclonal band in anti-myelin oligodendrocyte glycoprotein (MOG) antibody associated disease

ObjectiveTo analyze the immune parameters of cerebrospinal fluid (CSF) and oligoclonal band (OCB) type in patients with anti-myelin oligodendrocyte glycoprotein (MOG) antibody-associated diseases (MOGAD). MethodsPatients who were seropositive for MOG-IgG and diagnosed with MOGAD according to the diagnosis criteria in the Department of Neurology, Huashan Hospital, Fudan University from December 2020 to June 2022 were retrospectively included in this study. Complete clinical data, blood and cerebrospinal fluid samples were collected from all the participants. Paired serum and CSF MOG-IgG and autoimmune encephalitis antibody were assayed by Cell Based Assay (CBA) based on transfected target antigens. Paired serum and CSF albumin and IgG were detected by turbidimetric scattering method, and OCB was detected by standard operation procedure as described. ResultsA total of 86 patients (44 males and 42 females) with MOGAD were included in this study, with a median age of 30 years (range: 5–82 years). Among all the patients, 73 patients showed OCB type I, 12 patients showed OCB type II, and one patient showed OCB type III. The overall positive rate of CSF-OCB in MOGAD patients was 15.1 %. The 24-h intrathecal synthesis rate of CSF in the OCB-positive group (n = 13) was higher than that in the OCB-negative group [n = 73, 0.62 (0.26) vs 5.11 (13.67), P = 0.003]. Subgroup analysis revealed that the positive rates of CSF-OCB in the single MOG group (n = 61) and the group combined with other antibodies (n = 25) were 14.8 % and 16.0 %, respectively. The incidence of meningoencephalitis (13/61 vs 13/25, P = 0.011) was significantly different between the two groups. The proportion of patients with high (≥1:32) or low (≤1:10) CSF MOG-IgG also showed significant difference in the group combined with other antibodies (P = 0.032). Optic neuritis was more common in the relapse course group (n = 49) than the monophasic course group (n = 37, P < 0.001) No significant diferences of CSF immune parameters were found in the MOG-IgGserum+/CSF− group and the MOG-IgGserum+/CSF + group, and the titer of MOG-IgG in the serum or CSF did not influence CSF immune parameters in different subgroups. ConclusionThe overall positive rate of CSF-OCB in MOGAD patients was 15.1 %. The 24-h intrathecal synthesis rate of cerebrospinal fluid in the OCB-positive group was higher than that in the OCB-negative group. This study illustrated OCB characterization in MOGAD patients, and will shed light on the standardization of OCB test in the study of immune diseases.

Comparing clinical features, severity and prognosis of autoimmune encephalitis and with and without oligoclonal bands.

This study aimed to examine the clinical distinctions among patients diagnosed with autoimmune encephalitis (AE) based on the presence or absence of cerebrospinal fluid (CSF) oligoclonal bands (OCBs). Additionally, it sought to explore the relationship between OCBs and the severity and prognosis of autoimmune encephalitis. A retrospective analysis was conducted on 94 patients diagnosed with AE at the People's Hospital of Zhengzhou University between October 2016 and June 2022. The patients were divided into OCB-positive and OCB-negative groups based on CSF-OCBs. Patient severity at admission was assessed utilizing the Clinical Assessment Scale for Autoimmune Encephalitis (CASE) and the modified Rankin scale (mRS). Additionally, some oligoclonal-positive patients underwent dynamic longitudinal analysis of cerebrospinal fluid test indices. The mRS score was ultimately employed to evaluate patients' short-term prognosis (6 months) and long-term prognosis (at least 12 months) following immunotherapy. Of the 94 patients, 34 (36.2%) belonged to the OCB-positive group, while 60 (63.8%) belonged to the OCB-negative group. The group with anti-n-methyl-d-aspartate receptor (anti-NMDAR) encephalitis exhibited the highest rate of oligoclonal positivity at 27 (49.1%), followed by anti-aminobutyric acid B receptor (GABABR) encephalitis with 4 cases (30.8%), anti-contactin-associated protein-like 2 (CASPR2) encephalitis with 2 cases (20%), and anti-leucine-rich glioma inactivating protein 1 (LGI1) encephalitis with 1 case (6.25%). No statistically significant differences were found between the two groups regarding gender, age, prodromal symptoms, psychiatric disorders, seizures, language disorders, motor dysfunction, cognitive dysfunction, tumor incidence, and magnetic resonance imaging (MRI) abnormalities (p > 0.05). The OCB-positive group exhibited higher rates of autonomic dysfunction, intensive care unit (ICU) admission, CSF leukocytes, and IgG index compared to the OCB-negative group (p < 0.05). Additionally, the OCB-positive group had significantly higher median CASE and mRS scores prior to immunotherapy than the OCB-negative group (p < 0.001 and p < 0.001). Furthermore, in both short-term follow-up and long-term follow-up, the OCB-positive group had a significantly lower proportion of patients with a favorable prognosis compared to the OCB-negative group (50% vs. 71.7, 61.8% vs. 83.3%; p = 0.036, p = 0.002). Autonomic dysfunction, ICU admission, leukocytes in the cerebrospinal fluid, and elevated IgG index are more commonly observed in OCB-positive patients. OCB-positivity has also been linked to the severity and prognosis of AE, making it a potential biomarker. Initial OCB testing aids clinicians in identifying potentially critically ill patients early and monitoring disease progression, thereby optimizing clinical treatment decisions.

Cerebrospinal fluid oligoclonal immunoglobulin gamma bands and long-term disability progression in multiple sclerosis: a retrospective cohort study

Multiple sclerosis (MS) patients with immunoglobulin gamma (IgG) oligoclonal bands (OCB) in the cerebrospinal fluid (CSF) have different genetic backgrounds and brain MRI features compared to those without. In this study, we aimed to determine whether CSF-OCB status is associated with long-term disability outcomes. We used Swedish MS register data on clinically definite MS patients with known OCB status. Date of birth, age at MS onset, and time to sustained Expanded Disability Status Scale (EDSS) milestones 3, 4, and 6; time to conversion to secondary progressive (SP) MS, sex, and immunomodulatory treatment (IMTs) duration were collected. Multivariate Cox regression models were used to investigate the association between OCB status and risk of reaching each milestone. The OCB-positive group reached disability milestones at an earlier time and younger age. OCB-positivity significantly increased the risk of reaching EDSS 3.0 (HR = 1.29, 95% CI 1.12 to 1.48, P < 0.001) and 4.0 (HR = 1.38, 95% CI 1.17 to 1.63, P < 0.001). The OCB-positive group had a 20% higher risk of conversion to SPMS. CSF-OCB presence is associated with higher risk of reaching EDSS milestones and conversion to SPMS. Our findings suggest higher disease modifying effect of OCB presence in the early inflammatory stages of MS.

Kappa Index Versus CSF Oligoclonal Bands in Predicting Multiple Sclerosis and Infectious/Inflammatory CNS Disorders.

Background: Cerebrospinal fluid (CSF) kappa free light chains (KFLC) are gaining increasing interest as markers of intrathecal immunoglobulin synthesis. The main aim of this study was to assess the diagnostic accuracy (AUC) of the kappa index (CSF/serum KFLC divided by the CSF/serum albumin ratio) compared to CSF oligoclonal IgG bands (OCB) in predicting Multiple Sclerosis (MS) or a central nervous system infectious/inflammatory disorder (CNSID). Methods: We enrolled patients who underwent a diagnostic spinal tap throughout two years. KFLC levels were determined using a Freelite assay (Binding Site) and the turbidimetric Optilite analyzer. Results: Of 540 included patients, 223 had a CNSID, and 84 had MS. The kappa index was more sensitive (0.89 versus 0.85) and less specific (0.84 versus 0.89), with the same AUC (0.87) as OCB for MS diagnosis (optimal cut-off: 6.2). Adding patients with a single CSF IgG band to the OCB-positive group slightly increased the AUC (0.88). Likewise, the kappa index (cut-off: 3.9) was more sensitive (0.67 versus 0.50) and less specific (0.81 versus 0.97), with the same AUC (0.74) as OCB, for a CNSID diagnosis. Conclusion: The kappa index and CSF OCB have comparable diagnostic accuracies for a MS or CNSID diagnosis and supply the clinician with useful, complementary information.

Advanced MRI features in relapsing multiple sclerosis patients with and without CSF oligoclonal IgG bands

Oligoclonal IgG bands (OCB) in cerebrospinal fluid (CSF) are important in diagnosis of multiple sclerosis (MS). We evaluated the MRI features of clinically definite MS subjects with and without CSF-OCB. Relapsing MS subjects were recruited from a prospective registry in a university center. CSF-OCB were detected using isoelectric focusing and lgG-specific immunofixation. MRI metrics including brain volumes, lesion volumes and microstructural measures, were analyzed by FMRIB Software Library (FSL) and Statistical Parametric Mapping (SPM). Seventy-five subjects with relapsing MS were analyzed. Forty-four (59%) subjects had an interval MRI at around 1 year. CSF-OCB were detected in 46 (61%) subjects. The OCB-positive group had a higher proportion of cerebellar lesions than the OCB-negative group (23.9% vs. 3.4%, p = 0.057). Except for amygdala volumes which were lower in the OCB-positive group (p = 0.034), other regional brain volumes including the subcortical deep gray matter and corpus callosum were similar. The two groups also showed comparable brain atrophy rate. For DTI, the OCB-positive group showed significantly higher mean diffusivity (MD) value in perilesional normal-appearing white matter (p = 0.043). Relapsing MS patients with and without CSF-OCB shared similar MRI features regarding volumetric analyses and DTI microstructural integrity.

Cerebrospinal fluid and urinary biomarkers in multiple sclerosis

Biomarkers with the potential for longitudinal measurements are needed in multiple sclerosis (MS). Urine is easy to collect, and repeated sampling is possible. 39 paired CSF and urine samples were taken. Oligoclonal bands (OCBs) were measured in CSF. Kappa and lambda free light chain (FLC), neopterin and ubiquitin C-terminal hydrolase-L1 (UCHL1) were measured in CSF and urine. 16/39 samples had OCBs unique to the CSF. CSF FLC levels (P < 0.0001) were higher in OCB-positive subjects, with no difference in urinary FLC. CSF and urinary FLC did not correlate. There were a significant correlation between total CSF FLC and CSF neopterin in MS samples (correlation coefficient = 0.588, P = 0.016) and a strong correlation between CSF lambda FLC and CSF neopterin in MS samples (correlation coefficient = 0.875, P < 0.001). There was a strong correlation between urinary neopterin/creatinine levels and urinary total FLC/protein levels (correlation coefficient = 0.452, P = 0.004). Only three CSF samples (8%) had detectable levels of UCHL1. 18/38 (48%) (8/15 MS and 10/23 control) urine samples had detectable levels of UCLH1. This study confirms the relationship between CSF OCBs and CSF FLCs, highlighting the importance of intrathecal B- and plasma-cell activation in MS. There is a relationship between CSF FLC and CSF neopterin in MS, highlighting the multifaceted immune activation seen in MS. Correlations in the OCB-positive group highlight the multifaceted immune activation seen in MS. Further studies are required to evaluate CSF and urinary biomarkers.

The Significance of HLA DRB1*1501 and Oligoclonal Bands in Multiple Sclerosis: Clinical Features and Disability

The aim of the present study was to determine the value of immunogenetic risk factors and to estimate their relationship with the clinical features and disability status of patients with multiple sclerosis in a Lithuanian population. This was a prospective study of 80 patients with multiple sclerosis. The diagnosis of multiple sclerosis was based on the revised McDonald criteria. Oligoclonal bands (OCBs) of immunoglobulin G (IgG) were tested using isoelectric focusing and IgG specific immunofixation. HLA DRB1 alleles were genotyped using polymerase chain reaction. Of all patients, 55% were positive for OCBs and 56% for HLA DRB1*1501. OCB-positive patients with multiple sclerosis had higher EDSS scores than their OCB-negative counterparts at onset of the disease (3.93±1.21 and 3.36±0.96 points, respectively; P=0.02) and during the last visit (4.31±2.06 and 3.09±1.98 points, respectively; P=0.009). The mean relapse rate was higher in the OCB-positive group compared with OCB-negative group (1.45±0.69 and 0.58±0.64, respectively; P=0.001). OCB-positive patients had higher IgG index compared with OCB-negative patients (P=0.0001). No relationship was found between HLA DRB1*1501 antigen status and the clinical features or EDSS score, and presence or absence of OCB in the present subset of patients with multiple sclerosis. The presence of oligoclonal bands in the cerebrospinal fluid of the patients with multiple sclerosis was associated with the greater number of exacerbations, higher degree of disability, and higher IgG index. There were no significant associations between the presence of HLA DRB1*1501 allele and the clinical symptoms, course of disease, or disability score.

Presence of CSF oligoclonal bands (OCB) is associated with the HLA-DRB1 genotype in a West Australian multiple sclerosis cohort

High-resolution HLA-DRB1 genotyping was performed in 97 OCB-positive and 68 OCB-negative cases with demyelinating disease to determine the influence of HLA-DRB1 alleles on the presence of OCB in a West Australian multiple sclerosis (MS) cohort. Carriage of the HLA-DRB1*1501 allele was associated with both OCB-positive and OCB-negative MS compared with controls, but more strongly with the OCB-positive group, and increased the likelihood of having OCB 2.1-fold with evidence of a dominant dose–effect. The HLA-DRB1*0301 allele was negatively correlated with OCB, with all homozygotes OCB-negative, suggesting a possible recessive protective effect of HLA-DRB1*0301. There was no significant correlation between OCB and the DRB1*04 alleles which have been associated with OCB-negative MS in previous Swedish and Japanese studies. Evidence of allelic interactions was found with HLA-DRB1*1501/*1301 heterozygotes having a reduced frequency of OCB and HLA-DRB1*0301/*0401 heterozygotes all being OCB-negative. These findings confirm the strong association between HLA-DRB1*1501 and OCB which has been found in other populations but indicate that the influence of other HLA-DRB1 alleles varies in different populations. Our study is the first to show that HLA-DRB1 allele interactions and dose–effects influence the frequency of OCB.

HLA-related subpopulations of MS in Japanese with and without oligoclonal IgG bands. Human leukocyte antigen.

Oligoclonal IgG bands (OCB) are present in most patients with MS in Western countries; however, in Japanese MS patients, the OCB-positive rate is not as high. A relationship between immunogenetic backgrounds, namely, human leukocyte antigen (HLA) DR2 and DR4 positivity, and OCB production in MS patients from Hokkaido, the northernmost island of Japan, has been previously suggested by the authors. To investigate the role of OCB in Japanese MS and to verify the interaction between immunogenetic backgrounds and OCB positivity. OCB, DR2(15), and DR4 positivity were studied in 45 patients with newly diagnosed MS. In addition to confirming the authors' previous findings, the clinical and demographic features, MRI findings, OCB positivity, and DRB1*15 and DRB1*04 polymorphisms of an expanded data set of 99 MS patients were investigated by using multivariate analysis. Patients with opticospinal MS (OS-MS) were excluded from this study. A relatively low OCB-positive rate (53.3%), HLA-DR15 association with OCB-positive MS (p = 0.0044), and DR4 association with OCB-negative MS (p = 0.0410) were confirmed. DR15 was not associated with OCB-negative MS. Demographic features, disease course, and disability were similar in the OCB-negative and OCB-positive group, whereas there was a preponderance of women in the OCB-positive group. An independent negative association of DRB1*0405 (p = 0.0021, adjusted odds ratio = 0.21) with OCB positivity was found. MS is heterogeneous in its association with HLA alleles, and based on the immunogenetic differences, the MS patients in this population include at least two HLA-related subpopulations with and without OCB.