Diagnostic value of anti-mutated citrullinated vimentin antibody in rheumatoid arthritis / 中国现代医生

Objective To investigate the clinical diagnostic value of anti-cyclic citrullinated peptide(CCP)antibody,anti-mutated citrullinated vimentin(MCV)antibody and 25-hydroxyvitamin D[25-(OH)D]in rheumatoid arthritis(RA)patients.Methods A total of 466 patients with RA who were admitted the Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University from August 2016 to November 2021 were included in RA group,100 patients with other autoimmune diseases and metabolic diseases without RA were included in non-RA group,100 healthy subjects were included in control group.Serum anti-CCP antibody,anti-MCV antibody and 25(OH)D were detected in three groups.Receiver operating characteristic curve was drawn to analyze the diagnostic efficacy of anti-CCP antibody,anti-MCV antibody and 25(OH)D in RA.The correlation between anti-MCV antibody and clinical indexes in RA patients was analyzed.Results Serum anti-MCV antibody and anti-CCP antibody in RA group were significantly higher than those in non-RA group and control group(P<0.05).The serum 25(OH)D level in RA group was significantly lower than that in control group(P<0.05).The area under the curve(AUC)of anti-CCP antibody,anti-MCV antibody and 25(OH)D for the diagnosis of RA were 0.74,0.81 and 0.75,respectively.The AUC for the combined diagnosis of RA was 0.90,the sensitivity was 83.70%,and the specificity was 82.40%.Anti-MCV antibody was positively correlated with erythrocyte sedimentation rate and C-reactive proten(r=0.66,0.64,P<0.05),and negatively correlated with complement C3 and C4(r=-0.69,-0.62,P<0.05).Conclusion Anti-CCP antibody,anti-MCV antibody and 25(OH)D have good sensitivity and specificity for the diagnosis of RA,and anti-MCV antibody was helpful for the diagnosis of the disease activity.

An ultrapotent RBD-targeted biparatopic nanobody neutralizes broad SARS-CoV-2 variants

The wide transmission and host adaptation of SARS-CoV-2 have led to the rapid accumulation of mutations, posing significant challenges to the effectiveness of vaccines and therapeutic antibodies. Although several neutralizing antibodies were authorized for emergency clinical use, convalescent patients derived natural antibodies are vulnerable to SARS-CoV-2 Spike mutation. Here, we describe the screen of a panel of SARS-CoV-2 receptor-binding domain (RBD) targeted nanobodies (Nbs) from a synthetic library and the design of a biparatopic Nb, named Nb1-Nb2, with tight affinity and super wide neutralization breadth against multiple SARS-CoV-2 variants of concern. Deep-mutational scanning experiments identify the potential binding epitopes of the Nbs on the RBD and demonstrate that biparatopic Nb1-Nb2 has a strong escape resistant feature against more than 60 tested RBD amino acid substitutions. Using pseudovirion-based and trans-complementation SARS-CoV-2 tools, we determine that the Nb1-Nb2 broadly neutralizes multiple SARS-CoV-2 variants, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), Lambda (C.37), Kappa (B.1.617.1) and Mu (B.1.621). Furthermore, a heavy chain antibody is constructed by fusing the human IgG1 Fc to Nb1-Nb2 (designated as Nb1-Nb2-Fc) to improve its neutralization potency, yield, stability and potential half-life extension. For the new Omicron variant (B.1.1.529) that harbors unprecedented multiple RBD mutations, Nb1-Nb2-Fc keeps a firm affinity (KD < 1.0x10-12 M) and strong neutralizing activity (IC50 = 0.0017 nM). Together, we developed a tetravalent biparatopic human heavy chain antibody with ultrapotent and broad-spectrum SARS-CoV-2 neutralization activity which highlights the potential clinical applications.

Estimation of bias on result of self-developed biochemical test system / 临床检验杂志

Objective To inquire into the clinical acceptability of self-developed biochemical test system by comparing the results and bias estimation with the traceable assay system.Methods According to the requests of National Committee for Clinical Laboratory Standards (NCCLS) EP-9A, comparison test and bias estimation for self-developed test system and traceable Roche reference system (HITACHI 7180) were performed by using patient's sera. The self-developed system was set up as axle Y, the traceable Roche assay system as axle X and 1/2 CLIA (%) was used as the acceptable judge standard.Results The relationship of LDL-C between self-developed system and comparison system was inferior, so the results of LDL-C as well as the low values of HDL-C were of low acceptability. The comparabilities of results of ALT, urea, creatinine, TC, ApoA1 and ApoB were acceptable.Conclusion The self-developed test system must compare with traceable assay system, and estimate its clinical acceptability. The regression equation Y=bX+a can be used to correct the bias of test result.