Phosphorylated p38 mitogen-activated kinase in patients with pemphigus vulgaris: a case–controlled study

Abstract

Background Although the exact pathogenic mechanisms leading to blister formation in pemphigus vulgaris (PV) have not been fully elucidated, intracellular signaling following antibody binding has been found to be necessary for inducing cell-cell dissociation. The phosphorylated p38 mitogen-activated protein kinase (P38 MAPK) signaling pathway plays a major role in the modulation of immune-mediated inflammatory responses and therefore has been linked with several autoimmune diseases. Studies showed that activation of P38 MAPK plays a role in the acantholytic process in PV through changes in the quaternary structure and cytoskeletal rearrangements. Objective To determine the levels of p38 MAPK and its substrate [MAP kinase-activated protein kinase 2 (MAPKAPK2)] in the peripheral blood mononuclear cells of patients with PV in relation to both the clinical score and the antidesmoglein 3 antibodies. Patients and methods This study included 25 Egyptian patients with PV and 25 healthy controls, who were recruited from Cairo University Hospitals. Detailed history was documented, and the severity of the diseases was determined by pemphigus disease area index score in each patient. Blood samples were obtained from all participants. Then, determination of the expression of p38 MAPK and its substrate MAPKAPK2 on peripheral mononuclear cells was done using flow cytometry, with measurement of antidesmoglein 3 antibody using enzyme-linked immunosorbent assay technique. Results We detected that P38 MAPK and MAPKAPK2 were upregulated in patients with PV in comparison with controls (P=0.024 and P=0.002, respectively). There was a positive correlation between the anti-Dsg3 antibodies and P38 MAPK (r=0.591, P=0.004) and between disease severity (pemphigus disease area index score) and P38 MAPK (r=0.617, P=0.002) as well. Conclusion This study concluded that P38 MAPK and its substrate MAPKAPK2 have a role in the pathogenesis of PV. Moreover, P38 MAPK can be used as a marker for disease activity follow-up, as it was correlated with both disease severity and autoantibody level.

Keywords

• acantholysis
• autoantibody
• desmoglein
• pemphigus vulgaris
• signaling pathways