Mouse IgG1 Lambda Isotype Control Antibody [Alexa Fluor® 700]

Objective. To analyze the structure, specificity, and in vivo pathogenetic potential of 2 human anticardiolipin (aCL) monoclonal antibodies (MAb). Methods. Human aCL IgG MAb were generated from hybridized Epstein-Barr virus-induced B cell lines from a healthy subject (MAb 519) and from a patient with primary antiphospholipid syndrome (MAb 516). Studies of antigen-binding specificity and analysis of Ig V-gene mutations were carried out. The MAb were independently injected into mated female BALB/c mice, and their effect on pregnancy outcome was compared with that of MAb 57, a highly mutated and antigen-selected human IgG1 lambda rabies virus antibody. Results. Both MAb 519 and MAb 516 utilized minimally mutated V(H)DJ(H) and V(kappa)J(kappa) gene segments and bound cardiolipin and other anionic phospholipids in the absence of beta(2)-glycoprotein I (beta(2)-GPI). The mice injected with aCL MAb displayed a significantly higher rate of fetal resorption and a significant reduction in fetal and placental weight as compared with those injected with MAb 57. These findings were accompanied by a finding of placental human IgG deposition and necrosis in the aCL MAb-treated animals. Conclusion. The results of this study indicate that human aCL IgG that are beta(2)-GPI independent can induce pathology.

Guselkumab (Tremfya (TM)) is a human monoclonal IgG1 lambda antibody being developed by Janssen Biotech, Inc. that has been approved in the USA as a treatment for moderate-to-severe plaque psoriasis. Guselkumab inhibits the binding of interleukin 23 (IL-23) to its cell surface receptor, disrupting the type 17 helper T cell/IL-17 pathway. This article summarizes the milestones in the development of guselkumab leading to this first approval for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.