| Part ? The distribution of serum anti-AQP4 antibody in NMOSD and related diseases determined by cell-based assayAim:To explore the distribution of anti-aquaporin 4(AQP4)antibody and autoantibodies in neuromyelitis optica spectrum disorders(NMOSD)and related diseases,such as multiple sclerosis(MS),clinically isolated syndrome(CIS),and non-organ specific autoimmune disease(NOSA),and to evaluate the value of anti-AQP 4 antibody and autoantibodies in diagnosing NMOSD.Methods:The clinical profiles of 344 patients were collected in this study,including 104 patients with NMOSD,59 patients with MS,45 patients with CIS,52 patients with systenuc lupus erythematosus(SLE),22 patients with Sjogren Syndrome(SS),and 62 patients with other neurological diseases(OND)such as cerebral infarction,spinal cord infarction,encephalitis,facial neuritis,and etc.The levels of serum anti-AQP4 antibody in patients were detected using cell-based indirect immunofluorescence.The demographic distribution,data of diseases,the positive rate of anti-AQP4 antibody,the first index event,and the distributions of autoantibodies and complements were compared between groups.The diagnistic value of anti-AQP4 antibody and autoantibodies for N-MOSD was evaluated usingreceive operating characteristic curve(ROC).Results:The positive rate of anti-AQP4 antibody was obviously higher in NMOSD group(91.3%)than that in SS group(4,5%)and SLE group(3.8%)(P=0.000).The serum anti-AQP4 antibody was undetectable in MS group,CIS group,and OND group(P=0.00).However,the positive rate of antinuclear antibodies in NMOSD group was significantly lower than that in SS group(95.5%)and SLE group(92.3%)(P=0.00).The positive rate of anti-Ro52 antibody was lower in 36 patients with N-MOSD(34.6%)than that in SS patients(95.5%)(P=0.00).The positive rate of anti-SSA antibody was clearly lower in 27 patients with NMOSD(26%)than that in SS patients(95.5%)and SLE patients(61.5%)(P=0.00).The positive rate of anti-SSB antibody was lower in 9 patients with NMOSD than that in SS patients(40.9%)and SLE patients(25%)(P=0.00;P=0.01).The area under the curve(AUC)of serul anti-AQP4 antibody was 0.95(P=0.00),while the AUC of serum anti-Ro52 antibody was 0.6(P=0.00).However,the AUC values of the other autoantibodies have no statisticallysignificance,suggesting that the specificity and sensitivity of these autoantibodies were not significant in the diagnosis of NMOSD.Conclusion:The autoantibosies and anti-AQP4 antibody widely distributed in patients with NMOSD.In particular,the anti-AQP4 antibody and anti-Ro52 antibody were featured by high sensitivity and specifivity in diagnosing NMOSD.Part ? The correlative study on NMOSD complicated with autoantibodiesAim:To collect the clinical data of NMOSD patients with or without anti-AQP4 antibody and autoantibodies,and to further analyze the clinical characteristics of each group.Methods:According to the results of anti-AQP4 antibody and autoantibody detection,104 NMOSD patients were divided into four groups:anti-AQP4 antibody(-)and autoantibodies(-)group(double-negative group),anti-AQP4 antibody(+)and autoantibodies(-)group(anti-AQP4 antibody positive group),anti-AQP4 antibody(-)and autoantibodies(+)group(autoantibodies positive group),and anti-AQP4 antibody(+)and autoantibodies(+)group(double-positive group),among which the number of anti-AQP4 antibody(-)and autoantibodies(+)group was zero.The data were compared between groups about the sex ratio,onset age,first index event,recurrence frequency,annual rate of recurrence,EDSS scores for peak and final follow-up,time for EDSS score reaching 6,clinical manifestations(signs and symptoms),serum autoantibodies,complements,thyroid function and related antibodies,cerebrospinal fluid change,changes detected by MRI,VEP,drug treatment,and etc.The Kaplan-Meier curves were drawn for analyzing the cumulative probability of survival for NMOSD with anti-AQP4 antibody with/without autoantibodies at the first reccurrence and the stage with EDSS score of 6.Results:1.Double-positive group was composed of 56 patients with a sex ratio(1:13)different from single-positive group(11/28,P=0.00).The interval of the first recurrence was shorter in single-positive group(1-52 months)than that in double-negative group(2-79 months)and double-positive group(8-120 months)(P=0.02;P=0.03).The annual rate of recurrence was 71.8%after the first episode in single-positive group,which was higher than that in double-negative group(33.3%)and double-positive group(50%,P=0.03;P=0.03).The average annual rate of recurrence in double-negative group(ranging from 0.22 to 0.52 with an average of 0.35)was lower than that in single-positive group(ranging from 0.13 to 4 with an average of 0.67)and double-positive group(ranging from 0.11 to 2.4 with an average of 0.59)(P=0.05;P=0.03).The EDSS score in single-positive group during the final follow-up ranged from 0 to 8.5 with an average of 2.99,which was higher than that in double-positive group(ranging from 0 to 5 with an average of 2.01)(P=0.01).The differential of the EDSS score in single-positive group during the peak and final follow-up varied from 0 to 6.5 with an average of 2.23,which was lower than that in double-positive group(ranging from 0 to 6 with an average of 3.27)(P=0.00).2.The level of cerebrospinal fluid glucose in double-negative group(ranging from 2.6 to 5.3 mmol/L with an average of 3.8 mmol/L)was higher than that in single-positive and double-positive groups(P=0.05;P=0.01).3.The median value of thyroglobulin antibody in double-positive group was 3.6 IU/mL(ranging from 0.1 to 2523 IU/mL),which was obviously higher than that in single-positive group(P=0.02).The median value of C3 in double-positive group(ranging from 0.37 to 1.26 g/L with an average of 0.88 g/L)was lower than that in single-positive group(ranging from 0.7 to 1.77 g/L with an average of 1.01 g/L)(P=0.01).The median value of C4 in double-positive group(ranging from 0.03 to 0.27 g/L with an average of 0.15 g/L)was lower than that in single-positive group(ranging from 0.07 to 0.71 g/L with an average of 0.21 g/L)(P=0.01).4.The positive rate of antinuclear antibodies in double-positive group(82.1%)was higher than that in double-negative group(0%)and single-positive group(0%)(P=0.00;P=0.00).The positive rate of anti-Ro52 antibody in double-positive group(64.3%)was higher than that in double-negative group(0%)and single-positive group(0%)(P=0.00;P=0.00).The positive rate of anti-SSA antibody in double-positive group(48.2%)was higher than that in double-negative group(0%)and single-positive group(0%)(P=0.00;P=0.00).The positive rate of anti-SSB antibody of 9 patients in double-positive group(16.1%)was higher than that in single-positive group(0%)(P=0.00).5.Three patients had a headache in double-negative group,with a higher frequency(44.4%)than that in double-positive group(10.7%,P=0.01).Eighteen patients developed ophthalmalgia in double-positive group,with a higher frequency(32.1%)than that in single-positive group(10.3%,P=0.01).6.The brainmagnetic resonance imaging(MRI)showed no abnormal lesions in NMOSD patients in double-negative group,with an incidence rate of 0%that was lower in single-positive group(46.2%)and double-positive group(46.4%)(P=0.02;P=0.01).7.The proportion of patients treated with intravenous gamma globulin needles was 33.3%,which was higher than that in double-positive group(14.3%)(x2=4.84,P=0.03).8.The survival curve analysis demonstrated that the cumulative probability of survival of patients scored 6 for EDSS in double-positive group was clearly lower than that in the other two groups(x2=14.593,P=0.00).9.The survival curve analysis implied that the cumulative probability of first recurrence in single-positive group was higher than that in the other two groups(x2=7.627,P=0.022).Conclusion:The recurrence risk and disabled cumulative probability were higher in NMOSD patients with positive serum AQP4 antibody but not autoantibodies than those other groups.The annual rate of recurrence was obviously increased in NMOSD patients with positive serum anti-AQP4 antibody,which was independent of autoantibodies.Besides,intracranial lesions occurred more commonly in these patients than in patients with negative serum anti-AQP4 antibody.Part ? The correlative study on NMOSD complicated with NOSAAim:To compare the differences in the clinical features between NMOSDwithout NOSA and NMOSD complicated with NOSA,and to investigate the risk factors for the progression of NMOSD complicated with NOSA.Methods:According to whether was complicated with NOSA,104 NMOSD patients were divided into two groups:NMOSD without NOSA(i.e.NMOSD group)and NMOSD with NOSA(i.e.NMOSD+NOSA group).The relevant profiles of two groups were compared(same as Part ?).The multivariate logistic regression analysis was conducted to identify the risk factors for the progression of NMOSD+NOSA.The ROC curves were drawn for evaluating the value of anti-AQP4 antibody and autoantibodies in diagnosing NMOSD+NOSDA.Results:1.NMOSD+NOSA group were composed of 0 males and 22 females,a sex ratio(0:22)that was significantly lower than that in NMOSD group(16:66,P=0.02).The EDSS score of NMOSD+NOSA patients during the final follow-up ranged from 0 to 4 with an average of 1.48,which was lower than that of NMOSD patients(ranging from 0 to 6.5 with an average of 2.7)(t=583.5,P=0.01).In the first index event of NMOSD+NOSA patients,postpolar symptoms,such as nausea,emesis,hiccup,and etc.,appeared in 2 patients with a occurrence rate of 9.1%,which was lower than that in NMOSD patients(13.4%,P=0.02).2.The cerebrospinal fluid pressure,white blood cell counts,protein abundance,chloride levels,glucose levels,IgG index,and 24-hour intrathecal synthesis rate were similar between both groups(P>0.05).3.The median value of T4 in NMOSD+NOSA patients(ranging from 4.15 to 16 pmol/L)was 10.27 pmol/L,which was higher than that in NMOSD patients(ranging from 0 to 2509 pmol/L with a median of 0.9 pmol/L,P=0.02).Besides,the levels of C3 and C4 were lower in NMOSD+NOSA group than in NMOSD group(P=0.02).4.The positive rates of anti-nuclear antibody,anti-Ro52 antibody,anti-SSA antibody,anti-SSB antibody,and anti-dsDNA antibody were higher in NMOSD+NOSA than in NMOSD group(2.4%,P=0.02).5.The incidence rates of ophthalmodynia,dry eye,xerostomia,erythema,arthralgia,baldness,dental ulcer,and nephropathy in NMOSD+NOSA group were significantly higher than those in NMOSD group(P=0.00).6.The brain MRI examinations showed subcortical white matter lesions in deep cerebral hemispheres in 5 cases of N-MOSD+NOSA with an incidence rate of 22.7%,which was higher than that in NMOSD group(8%,P=0.02).7.The rate of hydroxychloroquine administration in NMOSD+NOSA patients was 22.7%,which was higher than that in NMOSD patients(0%,P=0.00).The rate of cyclophosphamide administration in NMOSD+NOSA patients was 22.7%,which was higher than that in NMOSD patients(1.2%,P=0.00).8.Multivariate logistic regression analysis revealed that variables like anti-SSA antibody and anti-Ro52 antibody were statistically different,suggesting that anti-SSA antibody and anti-Ro52 antibody were independent risk factors for the progression into NMOSD+NNOSA(P=0.00).9.The AUC of serum anti-SSA antibody was 0.88 with 95%Cl of 0.79-0.97(P=0.00).The AUC of serum anti-Ro52 antibody was 0.86 with 95%Cl of 0.77-0.94(P=0.00).Conclusion:NMOSD patients complicated with NOSA developed clinical signs and symptoms relevant to both diseases,among which Accumulation of the last neurological disabilityislower in NMOSD complicated with NOSA than in simple NMOSD.Autoantibodies were characteristic of high sensitivity and specificity in diagnosing NMOSD complicated with NOSA.Anti-SSA antibody and anti-Ro52 antibody were especially sensitive and specific in the diagnosis of NMOSD+NOSA and thus were considered as important independent risk factors for the progression into NMOSD+NOSA. |
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