IgD/FcδR is involved in T-cell acute lymphoblastic leukemia and regulated by IgD-Fc-Ig fusion protein.

T-cell acute lymphoblastic leukemia (T-ALL) has a poor prognosis as a result of severe immunosuppression and rapid tumor progression with resistance to conventional chemotherapy. Excessive IgD may play a role in T cell activation via IgD Fc receptor (FcδR). Here we aimed to investigate the effects of IgD in T-ALL and demonstrated the potential benefit by targeting IgD/FcδR in T-ALL patients with IgD-Fc-Ig fusion protein. In T-ALL patients' blood samples and cell lines, the level of IgD, the percentage of FcδR expressing cells and the binding affinity were determined by flow cytometry. T cell viability, proliferation and apoptosis were analyzed. A mouse xenograft model was used to evaluate the in vivo effect of IgD-Fc-Ig, an IgD-FcδR blocker. The levels of serum IgD and FcδR were abnormally increased in part of T-ALL patients and IgD could induce over-proliferation and inhibit apoptosis of T-ALL cells in vitro. FcδR was constitutively expressed on T-ALL cells. IgD-Fc-Ig showed similar binding affinity to FcδR and selectively blocked the stimulation effect of IgD on T-ALL cells in vitro. In vivo study exhibited that IgD-Fc-Ig may also have therapeutic benefit. IgD-Fc-Ig administration inhibited human T-ALL growth and extended survival in xenograft T-ALL mice. In conclusion, this work supports the idea of targeting IgD/FcδR in T-ALL patients with excessive IgD. IgD-Fc-Ig fusion protein might be a potential biological drug with high selectivity for T-ALL treatment.

IgD enhances the release of neutrophil extracellular traps (NETs) via FcδR in rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disorder affecting primarily the joints. Neutrophils and the release of neutrophil extracellular traps (NETs) contribute to the pathogenesis of RA. However, IgD, which was abnormally higher in RA, has not been studied for its pathological role in neutrophil activation and NETs formation. To investigate the effects of IgD on neutrophil activation and NETs formation via IgD receptor (FcδR), we collect peripheral blood of RA patients and established adjuvant-induced arthritis (AA) rat model. We found that the expression of FcδR on neutrophils was significantly higher in RA patients compared with healthy controls. As a specific marker of NETs, the level of citrullinated histone H3 was positively correlated with sIgD and FcδR in RA patients. IgD enhances the release of NETs and promotes the proliferation of fibroblast-like synoviocytes (FLS) from RA patients by activating neutrophils. As a competitive FcδR blocker, IgD-Fc-Ig fusion protein could significantly reduce NETs formation and FcδR expression on neutrophils in vitro. In vivo, IgD-Fc-Ig could restrain IgD-induced neutrophil activation and NETs formation, thus inhibited FLS proliferation in AA rats. Data presented here demonstrate that neutrophils could be triggered by IgD to release NETs and take part in FLS proliferation in RA patients with excessive IgD. Blocking IgD-FcδR could inhibit neutrophil activation and NETs formation, and represent an additional attractive novel therapeutic strategy for the treatment of RA.

In situ diagnostic analysis of the XVIII century Madonna della Lettera panel painting (Messina, Italy).

The scientific investigation of the techniques employed by the artist, such as composition of the paints, color palette, and painting style represents a fundamental pre-requisite in order to develop proper conservation and restoration strategies. In this context, the combined use of non-destructive, non-invasive in situ image and chemical analyses was here successfully employed for the investigation of the XVIII century Madonna della Lettera panel painting from the ancient Basilian abbey of Santa Maria di Bordonaro in Messina (Italy). The used techniques were visible, infrared (IR) and false-color infrared (FCIR) photography, X-ray radiography, X-ray fluorescence (XRF) and Raman spectroscopy. The goal was to obtain accurate information on materials and techniques originally used and possible later interventions, with particular regard to the nature of the painting materials. From the results, details of the artwork useful for restoration and conservation procedures were revealed. The identification of most of the artist's palette was also achieved: Prussian blue for blue color, lead white for white, umber for the brown, cinnabar for the red, and carbon black for the black color. The composition of different preparatory substrates was also investigated. The obtained results, other than constituting a crucial step for future restoration works, can be at the same time useful for the dating of the painting, that does not report the date and the artist's signature.