Identification of galectin-3 as an autoantigen in patients with IgG4-related disease.

BACKGROUND: The antigenic trigger that drives expansion of circulating plasmablasts and CD4+ cytotoxic T cells in patients with IgG4-related disease (IgG4-RD) is presently unknown. OBJECTIVE: We sought to sequence immunoglobulin genes from single-cell clones of dominantly expanded plasmablasts and generate recombinant human mAbs to identify relevant antigens in patients with IgG4-RD by using mass spectrometry. METHODS: Paired heavy and light chain cDNAs from dominant plasmablast clones were expressed as mAbs and used to purify antigens by using immunoaffinity chromatography. Affinity-purified antigens were identified by using mass spectrometry and validated by means of ELISA. Plasma levels of the antigen of interest were also determined by using ELISA. RESULTS: mAbs expressed from the 2 dominant plasmablast clones of a patient with multiorgan IgG4-RD stained human pancreatic tissue sections. Galectin-3 was identified as the antigen specifically recognized by both mAbs. Anti-galectin-3 autoantibody responses were predominantly of the IgG4 isotype (28% of the IgG4-RD cohort, P = .0001) and IgE isotype (11% of the IgG4-RD cohort, P = .009). No significant responses were seen from the IgG1, IgG2, or IgG3 isotypes. IgG4 anti-galectin-3 autoantibodies correlated with increased plasma galectin-3 levels (P = .001), lymphadenopathy (P = .04), total IgG level increase (P = .05), and IgG4 level increase (P = .03). CONCLUSION: Affinity chromatography using patient-derived mAbs identifies relevant autoantigens in patients with IgG4-RD. IgG4 galectin-3 autoantibodies are present in a subset of patients with IgG4-RD and correlate with galectin-3 plasma levels. The marked increases in levels of circulating IgG4 and IgE observed clinically are, at least in part, caused by the development of IgG4- and IgE-specific autoantibody responses.

Hematopoietic Stem Cells in Wound Healing Response.

Significance: Emerging evidence has shown a link between the status of hematopoietic stem cells (HSCs) and wound healing responses. Thus, better understanding HSCs will contribute to further advances in wound healing research. Recent Advances: Myeloid cells such as neutrophils and monocyte-derived macrophages are critical players in the process of wound healing. HSCs actively respond to wound injury and other tissue insults, including infection and produce the effector myeloid cells, and a failing of the HSC response can result in impaired wound healing. Technological advances such as transcriptome at single-cell resolution, epigenetics, three-dimensional imaging, transgenic animals, and animal models, have provided novel concepts of myeloid generation (myelopoiesis) from HSCs, and have revealed cell-intrinsic and -extrinsic mechanisms that can impact HSC functions in the context of health conditions. Critical Issues: The newer concepts include-the programmed cellular fate at a differentiation stage that is used to be considered as the multilineage, the signaling pathways that can activate HSCs directly and indirectly, the mechanisms that can deteriorate HSCs, the roles and remodeling of the surrounding environment for HSCs and their progenitors (the niche). Future Directions: The researches on HSCs, which produce blood cells, should contribute to the development of blood biomarkers predicting a risk of chronic wounds, which may transform clinical practice of wound care with precision medicine for patients at high risk of poor healing.

Cross-Linkable Fluorene-Diphenylamine Derivatives for Electrochromic Applications.

Multicolor electrochromic systems based on heat cross-linkable arylamine-substituted fluorene derivatives, FD and FDOMe, are reported. These derivatives with pendant vinyl groups have been synthesized by the Buchwald-Hartwig amination reaction and were well-characterized using various analytical and spectroscopic techniques such as NMR, ESI-MS, and single-crystal X-ray diffraction analysis. FD and FDOMe exhibited thermally activated cross-linking above their melting temperatures, which was confirmed through absorption, differential scanning calorimetry (DSC), FT-IR, and wide-angle X-ray diffraction (WAXD) techniques. Cross-linked FD films (FD-X) on ITO showed two reversible redox peaks at 0.74 and 0.91 V (versus Ag/AgCl) that correspond to the formation of radical cations and dications, respectively. The corresponding redox peaks were observed at 0.6 and 0.8 V for cross-linked FDOMe films (FDOMe-X). Spectroelectrochemical studies of the electrochromic films on ITO revealed multicolor electrochromism of FD-X (colorless-yellow-dark cyan) and FDOMe-X (colorless-brick red-blue) with a color contrast of ∼44% at 485 nm for FD-X and ∼63% at 500 nm for FDOMe-X and good switching stability between the neutral and oxidized states (>300 cycles) with low switching voltages (<0.9 V for the first oxidation and <1.3 V for the second oxidation). Furthermore, fabrication of electrochromic devices using FD-X and FDOMe-X on FTO substrate with PMMA-based solid electrolyte was demonstrated, where the devices exhibited reasonably low switching time between the redox states (<30 s) with good optical contrast.