Predictors of use and improvement in glycemic indices after initiating continuous glucose monitoring in real world: Data from Saudi Arabia

Background and aimsTo identify predictors of use and benefit from continuous glucose monitoring (CGM) in people with type 1 diabetes (T1D).MethodsPredictors of CGM use and changes in glycemic indices and other clinical parameters after initiating intermittently-scanned CGMs were examined in 116 individuals with T1D living in Saudi Arabia. Participants were categorized based on frequency of CGM sensor scanning at month 6 into: Frequent users (≥10 scans/day) and infrequent users (<10 scans/day).ResultsFrequent CGM users had an improvement in time in range (TIR) and time above range (TAR) at months 6 and 12; whereas infrequent users had comparable improvements but only at month 12. Individuals with baseline TIR <50% had a significant improvement in TIR and TAR; whereas those with baseline TIR ≥50% had a significant improvement only in time below range (TBR). Baseline TIR <50% and higher frequency of scans were predictive of improvement in TIR at month 6 (OR: 4.84, p <0.01, 1.05, p= 0.04; respectively); whereas baseline TBR was the only predictor of improvement in TBR (OR:1.24,p < 0.01). Being a woman, higher number of scans/day during the first 2 weeks of CGM use, and having a lower A1C at baseline predict being a frequent scanner at month 6 (OR: 2.81, p=0.04; 1.12, p <0.01; and 0.73, p <0.01; respectively).ConclusionsImprovement in glycemic control with CGM use can be predicted by: number of scans per day and baseline TIR and TBR in people with T1D.     

Characterization of human decidual mast cells and establishment of a culture system

Background

Although rodent decidual mast cells (MCs) reportedly play an important role in implantation and placenta formation, the characterization of human decidual MCs has been not well clarified. The aims of this study were to investigate the distribution and characteristics of MCs in human decidua and to establish a culture system for decidua-derived MCs.

Interplay between immune responses to HLA and non-HLA self-antigens in allograft rejection

Recent studies strongly suggest an increasing role for immune responses against self-antigens (Ags) which are not encoded by the major histocompatibility complex in the immunopathogenesis of allograft rejection. Although, improved surgical techniques coupled with improved methods to detect and avoid sensitization against donor human leukocyte antigen (HLA) have improved the immediate and short term function of transplanted organs. However, acute and chronic rejection still remains a vexing problem for the long term function of the transplanted organ. Immediately following organ transplantation, several factors both immune and non immune mechanisms lead to the development of local inflammatory milieu which sets the stage for allograft rejection. Traditionally, development of antibodies (Abs) against mismatched donor HLA have been implicated in the development of Ab mediated rejection. However, recent studies from our laboratory and others have demonstrated that development of humoral and cellular immune responses against non-HLA self-Ags may contribute in the pathogenesis of allograft rejection. There are reports demonstrating that immune responses to self-Ags especially Abs to the self-Ags as well as cellular immune responses especially through IL17 has significant pro-fibrotic properties leading to chronic allograft failure. This review summarizes recent studies demonstrating the role for immune responses to self-Ags in allograft immunity leading to rejection as well as present recent evidence suggesting there is interplay between allo- and autoimmunity leading to allograft dysfunction.     

Contributions of B cells to lupus pathogenesis

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies. This review summarizes first the results obtained in the mouse that have revealed how B cell tolerance is breached in SLE. We then review the B cell subsets, in addition to the autoAb producing cells, which contribute to SLE pathogenesis, focusing on marginal zone B cells, B-1 cells and regulatory B cells. Finally, we review the interactions between B cells and other immune cells that have been implicated in SLE, such as dendritic cells, macrophages, neutrophils and T cells.     

Regions recognized on the light chain of botulinum neurotoxin type A by T lymphocytes of SJL and BALB/c mice primed with inactivated toxin

Lymph node cells (LNC) from SJL (H-2^s) and BALB/c (H-2^d) mice primed once with inactivated botulinum neurotoxin type A (BoNT/A) were examined for their T-cell responses to each of 32 synthetic overlapping peptides (19 residues each, L1–L32) that encompass the entire L chain (residues 1–448) of BoNT/A. LNC of SJL gave strong responses to 6 regions on, L2 (residues 15–23), L10/11/12 (127–173), L19 (253–271) and L21 (281–299), and moderate to weak responses to L9 (113–131), L14/15 (183–215) and L27 (365–383). In BALB/c, LNC gave a substantial T-cell response only against peptide L12 (residues 155–173), and responded very weakly to 9 other peptides. The results were compared with the recognition profiles determined previously in these two strains after multiple BoNT/A injections. Overall responses to the L-chain peptides of T cells in later profiles were found to be somewhat weakened in SJL and stayed essentially at a similar level in BALB/c, although responses to BoNT/A increased. In SJL, response to L10 (127–145) remained the highest in the later profile. Strong responses against L12 (155–173) observed in both strains at early stage were reduced to an insignificant level. Cross-reactivity to tetanus neurotoxin by BoNT/A-specific T cells was observed in SJL but not in BALB/c. Design of an effective synthetic peptide vaccine will require incorporation of both T cell- and Ab-recognition elements of the BoNT molecule. Significance and possible implications of these results on BoNT/A-specific T-cell responses of BoNT-treated patients are discussed.     

Effects of intracellular antibodies to cGMP on responses of cortical neurons of awake cats to extracellular application of muscarinic agonists

Intracellular injection of specific antibody to cyclic 3',5'-guanosine monophosphate (cGMP-Ab) produced substantial decreases in input resistance (Rm) selectively in neurons of the motor cortex that had responded with increased resistance to prior application of muscarinic agents. Intracellular injection of nonspecific immunoglobulins (IgG) did not produce this effect. (Some nonspecific effects on spike production occurred in cells given IgG or cGMP-Ab.) The decrease in Rm may be interpreted as being consequential to a reduction in baseline amounts of active cGMP due to binding of cGMP with the injected antibody. In cells which demonstrated a prior increase in Rm following extracellular application of the muscarinic agonist, aceclidine, or acetylcholine, injection of antibody to cGMP also resulted in suppression of the increase in Rm to subsequent applications of these muscarinic agents. Some increases in firing rate to these agents continued to be observed after injection of cGMP-Ab. The results support the hypothesis that cGMP mediates effects of muscarinic neurotransmission on the conductances of neurons of the motor cortex of awake cats. Intracellular injection of antibodies to specific cellular elements is shown to be feasible in cortical neurons of awake cats and may prove a useful adjunct to future studies of neurotransmitter mechanisms.     

A focused salivary gland infection with attenuated MCMV: an animal model with prevention of pathology associated with systemic MCMV infection

While the salivary gland has been recognized as an important effector site of the common mucosal immune system, a useful model for studying anti-viral salivary gland immune responses in vivo and for exploring the role of the salivary gland within the common mucosal system has been lacking. Murine cytomegalovirus (MCMV) is a beta-herpesvirus that displays a strong tropism for the salivary gland and produces significant morbidity in susceptible mice when introduced by intraperitoneal (i.p.) inoculation. This study tested the hypothesis that MCMV morbidity and pathology could be reduced by injecting the virus directly the submandibular salivary gland (intraglandular (i.g.)), using either in vivo derived MCMV or the less virulent, tissue-culture-derived MCMV (tcMCMV). Peak salivary gland viral titers were completely unaffected by infection route (i.p vs. i.g.) after inoculation with either MCMV or tcMCMV. However, i.g. tcMCMV inoculation reduced viremia in all systemic tissues tested compared to i.p. inoculation. Furthermore, systemic organ pathology observed in the liver and spleen after i.p. inoculation with either MCMV or tcMCMV was completely eliminated by i.g. inoculation with tcMCMV. Cellular infiltrates in the salivary glands, after i.p. or i.g. inoculation were composed of both B and T cells, indicating the potential for a local immune response to occur in the salivary gland. These results demonstrate that a focused MCMV infection of the salivary gland without systemic organ pathology is possible using i.g. delivery of tcMCMV.     

Traumatic brain injury stimulates hippocampal catechol-O-methyl transferase expression in microglia

Outcome following traumatic brain injury (TBI) is in large part determined by the combined action of multiple processes. In order to better understand the response of the central nervous system to injury, we utilized an antibody array to simultaneously screen 507 proteins for altered expression in the injured hippocampus, a structure critical for memory formation. Array analysis indicated 41 candidate proteins have altered expression levels 24h after TBI. Of particular interest was catechol-O-methyl transferase (COMT), an enzyme involved in metabolizing catecholamines released following neuronal activity. Altered catecholamine signaling has been observed after brain injury, and may contribute to the cognitive dysfunctions and behavioral deficits often experienced after TBI. Our data shows that COMT expression in the injured ipsilateral hippocampus was elevated for at least 14 d after controlled cortical impact injury. We found strong co-localization of COMT immunoreactivity with the microglia marker Iba1 near the injury site. Since dopamine transporter expression has been reported to be down-regulated after brain injury, COMT-mediated catecholamine metabolism may play a more prominent role in terminating catecholamine signaling in injured areas.