Rabbit Anti-CD19 monoclonal antibody, clone KG100-0

Factors contributing to hematopoietic recovery following chimeric antigen receptor (CAR) T-cell therapy have not been well studied. In an analysis of 83 patients with hematologic malignancies treated with CAR T-cell therapy, we describe patterns of hematopoietic recovery and evaluate potentially associated factors. We included patients who received axicabtagene ciloleucel (n = 30) or tisagenlecleucel (n = 10) for B-cell lymphoma, CD19-28z CAR T therapy for B-cell acute lymphoblastic leukemia (NCT01044069; n = 37), or B-cell maturation antigen targeting CAR T cells for multiple myeloma (NCT03070327; n = 6). Patients treated with CAR T cells who had not progressed, died, or received additional chemotherapy had "recovered" (per definition in Materials and methods section) hemoglobin, platelet, neutrophil, and white blood cell counts at rates of 61%, 51%, 33%, and 28% at month 1 postinfusion and 93%, 90%, 80%, and 59% at month 3 postinfusion, respectively. Univariate analysis showed that increasing grade of immune effector cell-associated neurological syndrome (ICANS), baseline cytopenias, CAR construct, and higher peak C-reactive protein or ferritin levels were statistically significantly associated with a lower likelihood of complete count recovery at 1 month; a similar trend was seen for cytokine release syndrome (CRS). After adjustment for baseline cytopenia and CAR construct, grade >= 3 CRS or ICANS remained significantly associated with the absence of complete count recovery at 1 month. Higher levels of vascular endothelial growth factor and macrophage-derived chemokines, although not statistically significant, were seen patients without complete count recovery at 1 month. This remains to be studied further in larger prospective studies.

Regulatory B cells (Bregs) are unique subpopulations of B cells with immune-regulating or immune-suppressing properties and play a role in peripheral tolerance. Due to the current limitations of human Breg studies among periodontal diseases, in the present study, we tried to analyze the change in circulating Bregs, pro-inflammatory, and anti-inflammatory cytokines in patients with periodontitis. Peripheral blood from 55 patients with stage 2 periodontitis and 20 healthy controls was analyzed using flow cytometry to evaluate the frequency of CD19(+)CD24(+)CD38(+)Breg cells. ELISA was used to assess the serum levels of the pro-inflammatory cytokines, including interleukins (IL)-1 beta, IL-6, TNF-alpha, and anti-inflammatory cytokines including IL-10, IL-35, and TGF-beta. Increased proportions of Breg cells were observed in patients with stage 2 periodontitis compared to controls. Serum levels of cytokines were significantly higher in patients with periodontitis compared to controls. A significant positive correlation was observed between the frequencies of Breg cells and IL35 levels, IL10 levels, and TGF-beta. In conclusion, our results suggest that the increase in peripheral Breg cells and serum cytokine levels among periodontitis patients seems to be closely associated with disease progression, a possible link between periodontitis, and systemic inflammatory process.