Dermal dendritic cell number correlates with serum autoantibody titers in Brazilian pemphigus foliaceus patients

Abstract

Pemphigus foliaceus (PF) is an autoimmune bullous disease endemic in Brazil. Since serum IL-12 is increased in patients with PF and Langerhans cells (LC) produce IL-12, we titrated serum autoantibodies by indirect immunofluorescence, and quantified epidermal dendritic cells, known as LC, and dermal dendritic cells (DC). Biopsies of blistering lesions were obtained from 22 patients, 13 of whom were submitted to biopsy of both injured and of apparently healthy skin. The control groups consisted of skin from 8 cadavers and from 12 women submitted to breast plastic surgery. LC and DC were identified with anti-CD1a antibody and quantified by morphometric analysis. LC number in the lesion and in apparently healthy skin from PF patients was similar to that of both control groups. DC number in the injured skin (median = 0.94 DC/mm basement membrane) was higher than that of the cadaver group (median = 0.13 DC/mm basement membrane). In the 13 patients with biopsies of both injured and apparently healthy skin, LC and DC were present in larger numbers in the lesion. There was a direct correlation between DC number in the lesion of the PF group and serum autoantibody titers. This correlation was not observed for LC number. The increased number of DC in the lesion, as well as its direct correlation with serum autoantibody titers suggest the participation of DC in the pathogenesis of PF. The relationship between increased DC number and IL-12 in PF needs to be clarified.

Mast cells, Mast/Stem Cell Growth Factor receptor (c-kit/cd117) and IgE may be integral to the pathogenesis of endemic pemphigus foliaceus

“…All EPF patients fulfilled the established criteria for PF in Colombia [4,5] and in Brazil [2,3]. As controls, we utilized 30 skin biopsies from healthy individuals from the El Bagre endemic area (without any history of an atopic disorder).…”

“…The roles of IgG autoantibodies and complement in lesional EPF skin has been previously documented [1][2][3][4][5][6][7].…”

“…Endemic pemphigus foliaceus (EPF) is an autoimmune blistering skin disease presenting in well-defined geographic regions [1][2][3][4][5][6][7]. The roles of IgG autoantibodies and complement in lesional EPF skin has been previously documented [1][2][3][4][5][6][7].…”

Individual and epistatic effects of genetic polymorphisms of B-cell co-stimulatory molecules on susceptibility to pemphigus foliaceus

“…45 Interestingly, there is an increased number of dendritic cells in endemic PF lesions and this correlates with serum antibody titers. 46 Thereby, according to the results of functional studies, the À1C allele may increase expression of CD40 on keratinocytes and contribute to the pathogenesis of PF. The consistency of the associations or trends observed for GD, MS and PF is compatible with a minor effect of the CD40 genetic variability on autoimmune disease susceptibility.…”

Glucocorticoid Sensitivity and Proinflammatory Cytokines Pattern in Pemphigus

“…The pathophisiological mechanisms of acantholysis in endemic PF remain unclear despite of several studies [9][10][11]. While pemphigus is an antibody mediated disease, the role of T cells in its pathogenesis is being increasingly recognized [12].…”