Identification of unique molecular heterogeneity of human CD79, the signaling component of the human B cell antigen receptor (BCR), and synergistic potentiation of the CD79-targeted therapy of B cell tumors by co-targeting of CD79a and CD79b.

We identified unique molecular heterogeneity of CD79 of human B cell antigen receptor (BCR) that may open a new approach to the ongoing CD79b-targeted therapy of B cell tumors. The primary purpose of the present study is to gain new information valuable for the enhanced CD79-targeted therapy. The molecular heterogeneity of CD79 was identified by sequential immunoprecipitation of BCR by use of anti-CD79b monoclonal antibody (mAb) SN8 and anti-CD79a mAb SN8b. SN8 is the antibody component of polatuzumab vedotin, an anti-CD79b antibody drug conjugate, that has been widely used for therapy of diffuse large B-cell lymphoma (DLBCL). The sequential immunoprecipitation shows that anti-CD79b mAb will be able to react only with a subgroup of CD79 molecules while anti-CD79a mAb will react with another subgroup of CD79 molecules; CD79 is a disulfide-linked heterodimer of CD79a and CD79b. Therapeutic study of SCID mice bearing human B-cell tumor shows synergistic potentiation by co-targeting CD79b and CD79a. Furthermore, simultaneous targeting of PD-1 strongly potentiates CD79a/CD79b-targeted therapy of B cell tumors. Flow cytometry analyses of CD79a/CD79b on malignant B cells of patients may provide a method for selection of the candidate patients for the CD79a/CD79b dual targeting therapy.

Optimal cut-off point of waist circumference for the diagnosis of metabolic syndrome in Japanese subjects.

Metabolic syndrome (MetS) has been redefined by a new criterion in Japan, in which waist circumference cut-off points, that is 85 cm for men and 90 cm for women, are used; however, objections are rising against this criterion. The present study examined the criterion for waist circumference to predict the accumulation of the components of MetS. In the present study, we used data for 5972 Japanese people who received annual health examinations, and 621 men (16.3%) and 51 women (2.4%) were diagnosed as having MetS. A cut-off point as a predictor for two or more components of MetS was evaluated by the sensitivity/specificity and a receiver operating characteristic analysis. The optimal point of waist circumference was estimated as being approximately 84 cm for men and 80 cm for women. We therefore recommend revising the cut-off value for the criterion of MetS in women according to our results and studies from other investigators. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00020.x, 2010).