Pain in autoimmune inflammatory myopathies: a scoping review.

BACKGROUND: Pain is considered a priority for research by adult patients with autoimmune inflammatory myopathy (AIM) and their families. Our aim was to review the literature for studies reporting on pain in adult AIM and to summarise their findings. METHODS: A scoping review was conducted searching for studies in PubMed and MEDLINE including more than five adult patients with AIM and assessing pain using a patient-reported outcome measure. Study population characteristics, pain measurement and clinical correlates of pain were extracted using a standardised protocol. RESULTS: The search strategy identified 2831 studies with 33 meeting inclusion criteria. Most studies used visual analogue scales (n=14) and/or the Medical Outcomes Study 36-Item Short Form Bodily Pain Scale (n=17). Frequency of pain and/or myalgias ranged from 64% to 100%. Subjects with AIM had significantly more pain than the general population and comparable pain to other chronic rheumatic diseases. Insufficient results were available to identify significant clinical correlates of pain in AIM. CONCLUSION: This review suggests that the burden of pain in AIM is considerable. Still, due to the heterogeneity and low quality of the evidence, significant knowledge gaps persist. Studies are needed to characterise pain trajectories of patients with AIM.

Serine Is an Essential Metabolite for Effector T Cell Expansion.

During immune challenge, T lymphocytes engage pathways of anabolic metabolism to support clonal expansion and the development of effector functions. Here we report a critical role for the non-essential amino acid serine in effector T cell responses. Upon activation, T cells upregulate enzymes of the serine, glycine, one-carbon (SGOC) metabolic network, and rapidly increase processing of serine into one-carbon metabolism. We show that extracellular serine is required for optimal T cell expansion even in glucose concentrations sufficient to support T cell activation, bioenergetics, and effector function. Restricting dietary serine impairs pathogen-driven expansion of T cells in vivo, without affecting overall immune cell homeostasis. Mechanistically, serine supplies glycine and one-carbon units for de novo nucleotide biosynthesis in proliferating T cells, and one-carbon units from formate can rescue T cells from serine deprivation. Our data implicate serine as a key immunometabolite that directly modulates adaptive immunity by controlling T cell proliferative capacity.

Role of Rho-GTPases and their regulatory proteins in glomerular podocyte function.

Podocytes play a critical role in maintaining glomerular permselectivity. It has been long recognized that their intricate actin-based structures are tightly associated with their normal function; however, the precise mechanisms by which podocytes form and maintain their complex structure had been poorly understood until the intensive investigations on podocyte biology began in 1998, triggered by the breakthrough discovery of nephrin. This review summarizes the recent discoveries of the molecular mechanisms by which the actin cytoskeleton is regulated in podocytes. A particular focus will be on the role of the Rho-family of small GTPases, represented by RhoA, Rac1, and Cdc42. Rho-GTPases are known for their versatile cellular functions, most importantly for the actin regulatory roles. We will also discuss the potential roles of the 3 groups of proteins known to regulate Rho-GTPases, namely GTPase-activating proteins, guanine nucleotide exchange factors, and guanine nucleotide dissociation inhibitors.