Positive frequency of autoantibodies in multiple sclerosis patients Are they associated with therapy?

BACKGROUND： Humoral autoimmunity in patients with multiple sclerosis is often asymptomatic and transient during interferon therapy. OBJECTIVE： To analyze the frequency of positivity to autoantibodies in multiple sclerosis patients and to clarify whether it is modified by immunomodulating therapy. DESIGN： A retrospective study.TIME AND SE＇rrlNG： The study was performed at the Multiple Sclerosis Center, Department of Neurosciences, Salerno Hospital, Italy, between 2005 and 2007. PARTICIPANTS： A total of 169 multiple sclerosis patients were included, 57 males and 112 females Individuals were mainly outpatients and were usually tested yearly for autoantibodies. Patients with previous immunological diseases were excluded from statistical evaluation. METHODS： The frequency of positivity was calculated in patients grouped for gender, multiple sclerosis clinical parameters, magnetic resonance imaging features and disease modifying therapy. A total of 113 patients were treated with beta interferons. MAIN OUTCOME MEASURES： Frequency of positivity to any autoantibody. Prevalences and incidences were calculated.RESULTS： The overall prevalence of autoantibodies within 3 years was 47.3%. In multiple sclerosis patients who were untreated or treated with drugs other than interferons, the prevalence was higher, and greater positivity to autoantibodies was seen in patients treated with interferons [odds ratio （95% confidence interval）, 2.87 （1.5 - 5.2）, P 〈 0.05 - 0.01]. Multiple regression analysis showed a significant association of the positivity to autoantibodies with interferon therapy, rather than gender, relapse or magnetic resonance imaging. CONCLUSION： Interferon therapy is associated with significantly higher frequency of autoantibodies in patients with multiple sclerosis. The differences among the therapies are not influenced by other variables such as gender or clinical pattern.

PTPRC(CD45)C77G突变对撒丁尼亚患者多发性硬化的易感性并无影响

A linkage and association of the CD45 (protein tyrosine phosphatase, receptor type C) C77G polymorphism and multiple sclerosis (MS) has been found in some s tudies but not in others. We analysed the C77G polymorphism in MS patients from the genetically homogeneous population of Sardinia. Using the ransmission disequ ilibrium test, the mutation has been sought in 241 patients and 217 healthy sibs (HS) from singleton MS families and it was found in 5 (2.07%) affected and 3 ( 1.38%) HS from 7 heterozygous parents (1.45%). Transmission of the G77 allele was 71.4%(TDT = 1.3, P = 0.26) in patients and 50%(TDT = 0, P = 1) in HS. Str atifying families according to carriage of MS predisposing (DR+) or not predi sposing(DR ) HLA DR DQ genotype in patients, percentage of G77 transmission t o DR+patients was 33 (TDT = 0.33, P = 0.56, Pc = 1.12), while it was 100 (TDT = 4, P = 0.045, Pc = 0.09) in the DR patients. We concluded that, despite the pr esence of CD45 G77 polymorphism in a few patients who did not carry the HLA DR DQ MS predisposing molecules, CD45 did not contribute to development of the d isease in Sardinian MS.

撒丁人群中HLA区域内基因位点间的相互作用影响多发性硬化症的病程

We examined the influence of alleles at the HLA loci, previously found to be associated with multiple sclerosis (MS) in Sardinia, on the clinical course of the disease in 835 relapsing (R) and 100 primary progressive (PP) patients. Multivariate analysis was carried out on predisposing 0301 or non-associated DPB1 alleles, susceptible or non-associated DRB1-DQB1 haplotypes, both predisposing and non-predisposing, and negatively and non-negatively associated D6S1683 alleles, taking interaction between them into account. Intra-patient analysis showed that the presence of the susceptible or protective D6S1683 allele interacting with predisposing DP 0301 modulated risk of PP disease. These findings suggest that a locus telomeric to HLA class I exerts an effect on alleles at the DPB1 locu s in modulating disease course.