Complex regional pain syndrome (CRPS) is a painful condition affecting one or more extremities of the body, marked by a wide variety of symptoms and signs that are often difficult to manage because the pathophysiology is incompletely understood. Thus, diverse treatments might be ineffective. A recent report revealed the presence of autoantibodies against differentiated autonomic neurons in CRPS patients. However, it remained unclear how the antibodies act in the development of CRPS. We therefore aimed to characterize these antibodies and identify target antigens. Functional properties of affinity-purified immunoglobulin G of control subjects or CRPS patients were assessed using a cardiomyocyte bioassay. Putative corresponding receptors were identified using antagonistic drugs, and synthesized peptide sequences corresponding to segments of these receptors were used to identify the target epitopes. Chinese hamster ovary cells were transfected with putative receptors to ensure observed binding. Further, changes in the intracellular Ca(2+) concentration induced by agonistic immunoglobulin G were measured using the Ca(2+)-sensitive fluorescent dye fura-2 assay. Herein, we demonstrate the presence of autoantibodies in a subset of CRPS patients with agonistic-like properties on the β(2) adrenergic receptor and/or the muscarinic-2 receptor. We identified these autoantibodies as immunoglobulin G directed against peptide sequences from the second extracellular loop of these receptors. The identification of functionally active autoantibodies in serum samples from CRPS patients supports an autoimmune pathogenesis of CRPS. Thus, our findings contribute to the further understanding of this disease, could help in the diagnosis in future, and encourage new treatment strategies focusing on the immune system.
BACKGROUND AND PURPOSEThe aim of this study was to clarify the mechanisms by which hydrogen sulphide (H2S) affects ion secretion across rat distal colonic epithelium.
EXPERIMENTAL APPROACHChanges in short-circuit current induced by the H2S-donor, sodium hydrosulphide (NaHS; 10 mmol·L
KEY RESULTSNaHS had a biphasic effect on overall currents across the basolateral membrane: an initial inhibition followed by a secondary stimulation. Both a scilliroside-sensitive action on the Na
CONCLUSIONS AND IMPLICATIONSATP-sensitive and Ca
2+-dependent basolateral K + conductances, the basolateral Na + -K + -pump as well as Ca 2+ transporters were involved in the action of H2S in regulating colonic ion secretion. [Ca 2+
Abbreviations
Hydrogen sulfide (H2S) is a well-known environmental chemical threat with an unpleasant smell of rotten eggs. Aside from the established toxic effects of high-dose H2S, research over the past decade revealed that cells endogenously produce small amounts of H2S with physiological functions. H2S has therefore been classified as a “gasotransmitter.” A major challenge for cells and tissues is the maintenance of low physiological concentrations of H2S in order to prevent potential toxicity. Epithelia of the respiratory and gastrointestinal tract are especially faced with this problem, since these barriers are predominantly exposed to exogenous H2S from environmental sources or sulfur-metabolising microbiota. In this paper, we review the cellular mechanisms by which epithelial cells maintain physiological, endogenous H2S concentrations. Furthermore, we suggest a concept by which epithelia use their electrolyte and liquid transport machinery as defence mechanisms in order to eliminate exogenous sources for potentially harmful H2S concentrations.
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