Journal of Dermatological Science 28 (2002) 219 – 226
Lack of involvement of P-glycoprotein (P-gp) in pemphigus
patients with poor response to steroid therapy
Hortensia de la Fuente
a,1
, Lourdes Baranda
b,2
, Martha I. Herna ´ndez
a
,
Bertha Torres-Alvarez
b
, Luis Llorente
c
, Esther Layseca
a
,
Roberto Gonza ´lez-Amaro
a,
*
a
Department of Immunology, Facultad de Medicina, U.A.S.L.P., Ae. V. Carranza 2405, 78210 San Luis Potosı ´, S.L.P., Mexico
b
Hospital Central Ignacio Morones Prieto, San Luis Potosı ´, S.L.P., Mexico
c
Instituto Nacional de Ciencias Me ´dicas y Nutricio ´n Salador Zubira ´n, Mexico, D.F., Mexico
Received 10 September 2001; received in revised form 19 November 2001; accepted 19 November 2001
Abstract
A small but significant fraction of pemphigus patients do not show an adequate response to steroid therapy.
P-glycoprotein (or P-gp) is a cell membrane efflux pump that expels drugs, including glucocorticoids, from the cytosol
to the extracellular medium. An increased expression and/or function of P-glycoprotein in lymphoid cells could
decrease the intracellular concentration of glucocorticoids, diminishing its therapeutic effects. The aim of this work
was to assess the expression and activity of P-glycoprotein in the mononuclear cells (MNC) from pemphigus patients
with good and poor response to steroid therapy. We studied 20 patients with pemphigus vulgaris, eight of them
classified as poor responders and 12 as good responders to steroid therapy. The expression and activity of
P-glycoprotein by MNC were quantified by flow cytometry, and P-glycoprotein mRNA levels were determined by a
semi-quantitative RT-PCR technique. We found that the expression of P-glycoprotein at both mRNA and protein
levels was similar in pemphigus patients with good and poor response to steroid therapy. Similar results were obtained
regarding P-glycoprotein activity. P-glycoprotein does not seem to be involved in the poor response to steroid
treatment seen in some pemphigus patients. It is important to investigate additional mechanisms that could account
for the glucocorticoid resistance seen in some pemphigus patients. © 2002 Elsevier Science Ireland Ltd. All rights
reserved.
Keywords: Lymphocytes; Multidrug resistance; Glucocorticoids; Bullous diseases
www.elsevier.com/locate/jdermsci
1. Introduction
Before the onset of corticosteroid therapy, most
patients with pemphigus vulgaris rapidly died.
Nowadays, the mortality rate in this autoimmune
disease has been reduced to 5–15% due to treat-
* Corresponding author. Tel./fax: +52-444-817-7706.
E-mail address: rgonzale@uaslp.mx (R. Gonza ´lez-Amaro).
1
This author contributed equally to this work.
2
This author contributed equally to this work.
0923-1811/02/$ - see front matter © 2002 Elsevier Science Ireland Ltd. All rights reserved.
PII:S0923-1811(01)00169-4