Despite the presumably high molecular and cellular heterogeneity of ILD, common protein regulations are observed, even across organ boundaries. The surprisingly high prevalence of MZB1-positive plasma B cells in tissue fibrosis warrants future investigations regarding the causative role of antibody-mediated autoimmunity in idiopathic cases of organ fibrosis, such as idiopathic pulmonary fibrosis.

Antibodies are central effectors of the adaptive immune response, widespread used therapeutics, but also potentially disease-causing biomolecules. Antibody folding catalysts in the plasma cell are incompletely defined. Idiopathic pulmonary fibrosis (IPF) is a fatal chronic lung disease with increasingly recognized autoimmune features. We found elevated expression of FK506-binding protein 11 (FKBP11) in IPF lungs where FKBP11 specifically localized to antibody-producing plasma cells. Suggesting a general role in plasma cells, plasma cell-specific FKBP11 expression was equally observed in lymphatic tissues, and in vitro B cell to plasma cell differentiation was accompanied by induction of FKBP11 expression. Recombinant human FKBP11 was able to refold IgG antibody in vitro and inhibited by FK506, strongly supporting a function as antibody peptidyl-prolyl cis-trans isomerase. Induction of ER stress in cell lines demonstrated induction of FKBP11 in the context of the unfolded protein response in an X-box-binding protein 1 (XBP1)-dependent manner. While deficiency of FKBP11 increased susceptibility to ER stress-mediated cell death in an alveolar epithelial cell line, FKBP11 knockdown in an antibody-producing hybridoma cell line neither induced cell death nor decreased expression or secretion of IgG antibody. Similarly, antibody secretion by the same hybridoma cell line was not affected by knockdown of the established antibody peptidyl-prolyl isomerase cyclophilin B. The results are consistent with FKBP11 as a novel XBP1-regulated antibody peptidyl-prolyl cis-trans isomerase and indicate significant redundancy in the ER-resident folding machinery of antibody-producing hybridoma cells.

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Background Wide complex tachycardia (WCT) associated with syncope as manifestation of an underlying, life-threatening arrhythmia might potentially be the harbinger of sudden cardiac death. Identifying the etiology of a WCT is imperative to provide appropriate treatment and prevent recurrence. Case summary We report the case of a 22-year-old male who had been experiencing hemodynamically significant wide complex tachycardia (WCT) leading to syncope at the age of 13 years. As the patient and the family rejected an electrophysiological (EP) study, he had received an implantable cardioverter defibrillator (ICD) for secondary prevention. After seven years experiencing multiple shocks, the patient finally gave consent to an EP study which identified a left-sided accessory atrioventricular pathway that was successfully ablated during the same procedure. Discussion The differential diagnosis of WCT might be challenging and includes both ventricular and supraventricular tachycardias. In young patients without structural heart disease experiencing WCT, an EP study should be offered before ICD implantation to make a final diagnosis with the potential to provide definitive treatment.