The Antigen Presenting Potential of CD21(low) B Cells
FRONTIERS IN IMMUNOLOGY
Authors: Reincke, Marlene E.; Payne, Kathryn J.; Harder, Ina; Strohmeier, Valentina; Voll, Reinhard E.; Warnatz, Klaus; Keller, Baerbel
Abstract
Human CD21(low) B cells are expanded in autoimmune (AI) diseases and display a unique phenotype with high expression of co-stimulatory molecules, compatible with a potential role as antigen-presenting cells (APCs). Thus, we addressed the co-stimulatory capacity of naive-like, IgM-memory, switched memory and CD27(neg)IgD(neg) memory CD21(low) B cells in allogenic co-cultures with CD4 T cells. CD21(low) B cells of patients with AI disorders expressed high levels of not only CD86, CD80, and HLA-DR (memory B cells) but also PD-L1 ex vivo and efficiently co-stimulated CD4 T cells of healthy donors (HD), as measured by upregulation of CD25, CD69, inducible co-stimulator (ICOS), and programmed cell death protein 1 (PD-1) and induction of cytokines. While the co-stimulatory capacity of the different CD21(low) B-cell populations was over all comparable to CD21(pos) counterparts of patients and HD, especially switched memory CD21(low) B cells lacked the increased capacity of CD21(pos) switched memory B-cells to induce high expression of ICOS, IL-2, IL-10, and IFN-gamma. Acknowledging the limitation of the in vitro setting, CD21(low) B cells do not seem to preferentially support a specific T-h effector response. In summary, our data implies that CD21(low) B cells of patients with AI diseases can become competent APCs and may, when enriched for autoreactive B-cell receptors (BCR), potentially contribute to AI reactions as cognate interaction partners of autoreactive T cells at sites of inflammation.
Rapid Antiretroviral Therapy (ART) Initiation at a Community-Based Clinic in Jackson, MS
AIDS RESEARCH AND THERAPY
Authors: Gomillia, Courtney E. Sims; Backus, Kandis V.; Brock, James B.; Melvin, Sandra C.; Parham, Jason J.; Mena, Leandro A.
Abstract
Background: Rapid antiretroviral therapy (ART), ideally initiated within twenty-four hours of diagnosis, may be crucial in efforts to increase virologic suppression and reduce HIV transmission. Recent studies, including demonstration projects in large metropolitan areas such as Atlanta, Georgia; New Orleans, Louisiana; San Francisco, California; and Washington D.C., have demonstrated that rapid ART initiation is a novel tool for expediting viral suppression in clinical settings. Here we present an evaluation of the impact of a rapid ART initiation program in a community-based clinic in Jackson, MS. Methods: We conducted a retrospective chart review of patients who were diagnosed with HIV at Open Arms Healthcare Center or were linked to the clinic for HIV care by the Mississippi State Department of Health Disease Intervention Specialists from January 1, 2016 to December 31, 2018. Initial viral load, CD4+ T cell count, issuance of an electronic prescription (e-script), subsequent viral loads until suppressed and patient demographics were collected for each individual seen in clinic during the review period. Viral suppression was defined as a viral load less than 200 copies/mL. Rapid ART initiation was defined as receiving an e-script for antiretrovirals within seven days of diagnosis. Results: Between January 1, 2016 and December 31, 2018, 70 individuals were diagnosed with HIV and presented to Open Arms Healthcare Center, of which 63 (90%) completed an initial HIV counseling visit. Twenty-seven percent of patients were provided with an e-script for ART within 7 days of diagnosis. The median time to linkage to care for this sample was 12 days and 5.5 days for rapid ART starters (p < 0.001). Median time from diagnosis to viral suppression was 55 days for rapid ART starters (p = 0.03), a 22 day decrease from standard time to viral suppression. Conclusion: Our results provide a similar level of evidence that rapid ART initiation is effective in decreasing time to viral suppression. Evidence from this evaluation supports the use of rapid ART initiation after an initial HIV diagnosis, including same-day treatment.