Implementation of X-ray fluorescence microscopy for investigation of elemental abnormalities in Amyotrophic Lateral Sclerosis

The abnormalities of metallochemical reactions may contribute to the pathogenesis of Amyotrophic Lateral Sclerosis (ALS). In the present work, an investigation of the elemental composition of the gray matter, nerve cells and white matter from spinal cord tissues representing three ALS cases and five non-ALS controls was performed. This was done with the use of the synchrotron microbeam X-ray fluorescence technique (micro-SRXRF). The following elements were detected in the tissue sections: P, S, Cl, K, Ca, Fe, Cu, Zn and Br. A higher accumulation of Cl, K, Ca, Zn and Br was observed in the nerve cell bodies than in the surrounding tissue. Contrary to all other elements, Zn accumulation was lower in the white matter areas than in the gray matter ones. The results of quantitative analysis showed that there were no general abnormalities in the elemental accumulation between the ALS and the control group. However, for individual ALS cases such abnormalities were observed for the nerve cells. We also demonstrated differences in the elemental accumulation between the analyzed ALS cases

Immune checkpoints and rheumatic diseases : what can cancer immunotherapy teach us?

The recent success of immune checkpoint blockade in cancer therapy illustrates the importance of the inhibitory receptors cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) and programmed cell death protein 1 (PD1) in the regulation of antitumour immune responses. However, blocking signalling by these inhibitory immune checkpoint receptors is also associated with substantial inflammatory effects that can resemble autoimmune responses, which is consistent with the role of these receptors in protecting the host from excessive inflammation. The human genome encodes over 300 inhibitory receptors, which represent as many opportunities to modulate inflammation in a disease-specific and tissue-specific manner. We argue that rheumatologists and oncologists should join forces to study these inhibitory immune molecules. An improved understanding of these immune checkpoints will enable both fields to make progress in exploiting inhibitory immune receptors therapeutically. In this Review, we discuss data from studies reporting the adverse inflammatory effects of cancer therapies that target immune checkpoints. We discuss the potential implications of these findings on the biological understanding of autoimmune rheumatic diseases and highlight therapeutic strategies that could be used to target inhibitory receptors for the treatment of these conditions