1.Distribution and significance of IgG subclasses of anti-CCP antibodies in sera from patients with rheumatoid arthritis
Jun LI ; Jiaxi CHEN ; Yimin SHEN ; Mengsha XIANG ; Chunlong WU ; Bo SHEN
Chinese Journal of Laboratory Medicine 2015;(8):548-551
Objective To evaluate the distribution and significance of IgG subclasses of anti-cyclic cirullinated peptide antibody (anti-CCP) in sera from patients with rheumatoid arthritis (RA).Methods A total of 83 patients with RA at the Department of Endocrinology of Taizhou Hospital , 51 disease controls and 50 healthy controls during the period from August 2012 to June 2013 were enrolled.The total serum IgG and IgG subclasses of anti-CCP antibodies were detected by antigen specific enzyme linked immune-sorbent assay( ELISA ).The prevalence and relative amount of IgG subclasses were calculated and compared.Statistical analysis was performed by χ2 test and Kruskal-Wallis H test.Results The positive rates of IgG subclasses of anti-CCP were anti-IgG 71.1%(59/83), anti-IgG1 78.3%(65/83), anti-IgG2 26.5%(22/83), anti-IgG3 60.2%(50/83), anti-IgG4 74.7%(62/83) respectively.The diagnostic value of anti-CCP-IgG1, anti-CCP-IgG3 and anti-CCP-IgG4 alone or combined (AUC =0.818-0.901),compared with anti-CCP-IgG(AUC=0.857), had no significant difference(Z=0.028-0.045,P>0.05).The DAS28 score of anti-CCP-IgG1(DAS28 =6.5), and anti-CCP-IgG4(DAS28 =6.5)positive in patients with RA were significantly higher than those in negative groups (DAS28=4.5,4.6)(U=396.0,427.5,P<0.01).The T28(T28=4.0,4.0)and SW28(SW28=4.0,4.0) results of CCP-IgG1and CCP-IgG4 positive in patients with RA were significantly higher than those in negative groups (T28=3.0,3.0,SW28 =3.0,3.0)(U=377.5,406.0,255.5,286.5,P<0.05).Conclusions The distribution of IgG subclasses of anti-CCP in sera from patients with RA was predominantly anti-CCP-IgG1, anti-CCP-IgG3 and anti-CCP-IgG4 associated with RA disease activity.However , whether joint detection of IgG subclasses can replace conventional anti -CCP is questionable.
2.Progress on pharmacokinetic study of antibody-drug conjugates.
Jianjun GUO ; Ran GAO ; Tengfei QUAN ; Lingyu ZHU ; Ben SHI ; Yongyue ZHAO ; Jing ZHU ; Mengsha LI ; Haizhi BU
Acta Pharmaceutica Sinica 2015;50(10):1203-9
Antibody-drug conjugate (ADC) is a new class of therapeutics composed of a monoclonal antibody and small cytotoxin moieties conjugated through a chemical linker. ADC molecules bind to the target antigens expressed on the tumor cell surfaces guided by the monoclonal antibody component. The binding ADC molecules can be internalized and subsequently the toxin moieties can be released within the tumor cells via chemical and/or enzymatic reactions to kill the target cells. The conjugation combines the merits of both components, i.e., the high target specificity of the monoclonal antibody and the highly potent cell killing activity of the cytotoxin moieties. However, such complexities make the pharmacokinetic and metabolic studies of ADCs highly challenging. The major challenges should include characterization of absorption, distribution, metabolism and excretion, investigation of underlying mechanisms, assessment of pharmacokinetic- pharmacodynamic relationship, and analytical method development of ADC drugs. This review will discuss common pharmacokinetic issues and considerations, as well as tools and strategies that can be utilized to characterize the pharmacokinetic and metabolic properties of ADCs.