Clinical Cohort And Glycoanalysis Of Immunoglobulin G Of Neuropsychiatric Lupus

Part Ⅰ:Exploring the risk factors and prognosis of transverse myelitis in systemic lupus erythematosusPurpose:We aimed to describe the clinical characteristics and outcomes of patients with transverse myelitis(TM)as a rare manifestation in systemic lupus erythematosus(SLE)and explore the risk factors and prognosis of SLE-related TM(SLE-TM).Methods:We conducted a retrospective case-control and cohort analysis.All patients with SLE-TM(58 patients)and 232 with SLE without TM,as a control group,were admitted to Peking Union Medical College Hospital between January 1993 and May 2021.Factors associated with the presence of SLE-TM and its prognosis were assessed using logistic regression and Cox proportional hazard models.Results:Multivariate analysis revealed that positive anti-Ro/Sjogren’ s syndrome A(anti-Ro/SSA)(<0.01)and increased erythrocyte sedimentation rate(ESR)(p<0.01)were associated with SLE-TM.Regarding prognosis,methylprednisolone(MP)pulse therapy within 2 weeks of onset(adjusted hazard ratio(AHR),2.12;95%confidence interval(CI),1.06-4.23;p=0.03)was associated with short-term neurological improvement.An American Spinal Injury Association Impairment Scale(AIS)grades of A,B,or C at onset(AHR,0.12;95%CI 0.05-0.28;p<0.001)and hypoglycorrhachia(AHR,0.29;95%CI,0.13-0.65;p<0.01)were associated with a short-term non-improved outcome.Conclusions:The positive anti-Ro/SSA antibodies and increased ESR may be associated with the presence of SLE-TM.An initial presentation with severe myelitis and hypoglycorrhachia appear to be predictors of a poor neurological outcome.Early steroid pulse therapy may improve the prognosis.Part Ⅱ:Relapse rates and risk factors for unfavorable neurological prognosis of transverse myelitis in systemic lupus erythematosus:A systematic review and meta-analysisBackground:Transverse myelitis(TM)is a rare but severe systemic lupus erythematosus(SLE)manifestation.To date,the prognostic factors for SLEassociated TM have been far less well-studied.There are also controversial data on the association of antiphospholipid antibodies(aPLs),Systemic Lupus Erythematosus Disease Activity Index(SLEDAI)score,decreased complement levels and longitudinal extensive transverse myelitis(LETM)with the outcome of TM.We aimed to review the potential prognostic factors and integrate relapse rates of observational studies for SLE-associated TM.Method:To review the prognosis for SLE-associated TM,relevant articles published up to July 30,2021,were comprehensively and systematically identified from PubMed,EMBASE and Web of Science databases.Five studies encompassing 283 patients with SLE-related TM were included in this meta-analysis;raw data were obtained from three studies.Results:The risk factors for unfavorable neurological outcome included demographic features,clinical characteristics,laboratory data,among which a grade of A,B or C.on the AIS at the onset of TM was associated with poor prognosis(OR:56.05,95%CI:6.29-499.25,P<0.001).The presence of hypoglycorrhachia was also correlated with a worse prognosis(OR:10.78,95%CI:3.74-31.07,P<0.001).No noticeable correlation was revealed between a poor outcome and positive aPLs and different aPLs profiles(anticardiolipin antibody[aCL],anti-β2-glycoprotein I[anti-β2GPI],lupus anticoagulant[LA]).The pooled 1-,3-and 5-year relapse rates were 22%(95%CI:0.13-0.31),34%(95%CI:0.22-0.47)and 36%(95%CI:0.14-0.58),respectively.No significant publication bias was found.Conclusion:A grade of A,B,or C on the AIS at initial TM and the presence of hypoglycorrhachia were found to be related to a worse prognosis in patients with SLE-associated TM.Notably,aPLs and different aPLs profiles may not suggest poor neurological outcome.The long-term relapse rate of patients with SLE-associated TM was relatively high.We recommend that treatment be stratified based on the initial severity of myelitis.For patients with severe myelitis,early intensive therapy may be initiated as soon as possible.Part Ⅲ:Predicting risk of neuropsychiatric involvements in systemic lupus erythematosusBackground:Neuropsychiatric systemic lupus erythematosus(NPSLE)is an important complication of systemic lupus erythematosus(SLE).We aimed to establish and validate a nomogram to predict the presence of NPSLE in patients with SLE.Methods:A multicenter,longitudinal cohort study was undertaken from January 2003 to May 2022.Data on 9606 consecutively evaluated patients diagnosed as having SLE was prospectively collected.Factors included in the nomogram were determined by Cox proportional hazard analysis and least absolute shrinkage and selection operator based on the training set.The accuracy and discriminative ability of developed models was evaluated by Harrell concordance index(C-index),and calibration curve.Its clinical utility was also evaluated using decision curve analysis(DCA),X-tile analysis and Kaplan-Meier curve,respectively in an independent validation set.Results:169 patients(1.76%)developed NPSLE during a median follow-up of 13.0 months(interquartile range,5.0-27.0 months).Of all included patients,6,777 and 2,829 patients were randomly divided into the training and validation groups,respectively.The final prediction model included 4 clinical features(age>30 years old at diagnosis,gender,renal disorder,elevated ESR)and 3 autoantibodies(anti-rRNP antibody positivity,ACL antibody positivity,LA antibody positivity).A 5-year and 10-year NPSLE probability-predictive nomogram was established.In the training and validation cohort,C-index were 0.78(95%CI,0.72-0.84)and 0.70(95%CI,0.61-0.79),respectively.Moreover,DCA also demonstrated that the nomogram was clinical beneficial.Additionally,participants were considered to have different risk levels of NPSLE presence based on the nomogram score(low-risk(<83),moderate-risk(83～)and high-risk(≥146))Conclusion:The nomogram achieved an optimal prediction of NPSLE in lupus patients.The risk for an individual patient to harbor NPSLE could be predicted by using this model,which can lead to a routine clinical assessments and rational therapeutic choice.Part Ⅳ:IgG glycosylation profiling of systemic lupus erythematosus with lectin microarrayBackground:Immunoglobulin G(IgG)glycosylation could modulate immunological effector functions and has been highly valued as potential disease biomarkers and therapeutic targets in systemic lupus erythematosus(SLE).Therefore,our study aimed to characterize the glycosylation profiles of serum IgG in patients with SLE.Methods:We used lectin microarrays containing 56 types of lectins to detect the glycan levels of serum IgG in 194 patients with SLE,100 patients with other autoimmune diseases(including 40 primary sjogren’s syndrome(pSS)and 60 rheumatoid arthritis(RA))used as disease controls(DCs),and 100 health controls(HCs).Differentially altered glycosylation patterns between SLE and control groups as well as between SLE subgroups were identified and further validated by lectin blot.Receiver-operating characteristic(ROC)curve analysis was used to assess the changes in serum IgG glycosylation profiles of SLE and controls.Results:The results revealed that the glycan level of galactose(binding PNA)was significantly increased and that the glycan level of GalNAc(binding Black bean crude)was significantly decreased in lupus patients compared to health controls and disease controls(all p<0.01).These differences were validated by lectin blot.For each lupus subgroup,glycan levels of IgG galactose(binding GHA)and GalNAc(binding CSA)were increased in neuropsychiatric lupus patients compared to the lupus patients without major organ involvement(all p<0.05).A higher binding level of CSA(preferred GalNAc)and a lower binding level of DSL(preferred GlcNAc)in the pulmonary arterial hypertension in lupus groups were compared to those without major organ involvement(p<0.05).The glycan level of galactose(binding PNA)was significantly increased in lupus nephritis patients compared to those without major organ involvement(p=0.02)Moreover,PNA levels exhibited a potential for discriminating patients with SLE from patients with pSS,with the cut-off value of PNA levels(1.2),an area under the curve of 0.775(p<0.001),a sensitivity of 92.8%,and a specificity of 65.0%.Conclusions:SLE patients showed disease-specific serum IgG glycosylation alterations.Aberrant galactose and GalNAc glycosylation might provide potential diagnostic value.Abnormal glycans may provide new insights into the role in SLE pathogenesis and its progression.