Biomarkers related to bullous pemphigoid activity and outcome

Abstract

Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease of the skin. Investigation of the BP-associated pathophysiological processes during the last decades showed that the generation of autoantibodies directed against the hemidesmosome proteins BP180 and BP230, a hallmark of the BP-associated autoimmune response, leads to the recruitment of inflammatory immune cells at the dermal-epidermal junction, and subsequently to the release of a large amount of inflammatory molecules involved in blister formation. Analysis in transversal and longitudinal studies of autoantibodies and inflammatory molecules production both at the time of diagnosis and under treatment was mainly performed within the serum but also in the blister fluid. Some autoimmune or inflammatory molecules expression was related to the presence of clinical signs, while others were mere bystanders. In this review, we focused on the autoimmune and inflammatory molecules that have been identified as potential biomarkers of BP development and outcome. K E Y W O R D Sautoantibodies, autoimmunity, bullous pemphigoid, cytokines, inflammation

Recent advances in the understanding and treatment of pemphigus and pemphigoid

“…Studies showing that antibodies targeting areas outside of NC16A had less capacity to deplete COL17 on keratinocytes than antibodies targeting NC16A suggest that the pathogenicity of autoantibodies in BP could be epitope dependent 61, 62 . Recent studies have offered some biomarkers for more efficient diagnosis and prediction of prognosis in pemphigoid 63, 64 .…”

New insights into pemphigoid diseases

“…Clinical investigations also include identification and validation of biomarkers for diagnosis, disease activity and severity, as well as prognostic markers for disease outcome. As BP180 is a molecule with multiple epitopes that may be responsible for different clinical manifestations, the resulting inflammatory processes are also associated with quantitative and qualitative modifications within the cytokines and the proteases profiles involved in the pathophysiological processes …”

Commentary on ‘Changing prevalence of diabetes mellitus in bullous pemphigoid: it is the dipeptidyl peptidase‐4 inhibitors’

“…2) encoding the O-glucosyltransferase 1 enzyme. 7 No mutation was found in KRT5, POFUT1 or PSENEN genes. In the epidermis, O-glucosyltransferase 1 is closely related to the Notch pathway, 4 a key regulator of epidermis maturation by controlling proliferation and differentiation of keratinocytes and melanocytes.…”

“…In the epidermis, O-glucosyltransferase 1 is closely related to the Notch pathway, 4 a key regulator of epidermis maturation by controlling proliferation and differentiation of keratinocytes and melanocytes. 7,8 Indeed, the transfer of glucose by POGLUT1 to the extracellular domain of the Notch receptors is essential for receptor activation. 7 O-glucosyltransferase 1 has two major domains, the N-terminal domain (residues 1-180) and C-terminal domain (residues 181-349), which together form the enzymatic binding site.…”

“…7,8 Indeed, the transfer of glucose by POGLUT1 to the extracellular domain of the Notch receptors is essential for receptor activation. 7 O-glucosyltransferase 1 has two major domains, the N-terminal domain (residues 1-180) and C-terminal domain (residues 181-349), which together form the enzymatic binding site. 4 The p.Arg272* nonsense mutation is located in the C-terminal domain and results in a truncated form of POGLUT1 with partial loss of the C-terminal domain (including the essential Arg279 involved in binding the UDP-glucose substrate) and complete loss of the C-terminal helix (residues 350-384) stabilizing the two domains.…”