ARTICLE
Sir,
Showing some clinical, morphological and immunological similarities,
both herpes gestationis (HG) and bullous pemphigoid (BP), which are autoimmune
skin disorders forming subepidermal blisters, are suspected as having
common pathogenic mechanisms [1]. However, HG and BP reveal a histopathological
difference: the existence of basal cell degeneration on light microscopy
in HG but not in BP [2]. This suggests that the degree of basal cell damage
in HG is higher than that in BP. We have reported a case of HG in this
journal [3]. We immunohistochemically compared the HG case to BP cases
using two anti-keratin antibodies to cytokeratin 5 (CK5) and cytokeratin
14 (CK14), which are basal cell-specific keratins.
Formalin-fixed and paraffin-embedded sections
of normal skin, a case of HG (case 1) and seven cases of BP (cases 2 to
8) listed in Table I were
examined with anti-keratin antibodies: MNF116 (Dako, CA) and LL002 (Neomarkers,
CA). The former reacts to cytokeratins 5, 6, 8, 17 and 19, and the latter
reacts to CK14. Deparaffinized sections were incubated in 1% H2O2/methanol
for 10 min to block endogenous peroxidase activity. Pretreatments with
0.1% trypsin at 37š C for 15 min and microwaving for 5 x 3 min were
performed for staining with MNF116 and LL002 respectively. They then were
stained by the avidin-biotin-complex system.
In normal epidermis, basal cells reacted strongly
to MNF116 and LL002. Suprabasal cells showed less MNF116 staining and
no reaction to LL002. In an area without blisters in case 1, MNF116 stained
almost all of the keratinocytes, and LL002 stained basal and immediately
suprabasal cells, whereas in the blister area, the basal cells, including
the cells with vacuolization reacted strongly to these antibodies, and
the staining in the suprabasal layers was reduced (Figs. 1A
and B). In addition, only MNF116 strongly stained the
granular layers in this area (Fig. 1A).
Both areas with and without blisters of all BP cases revealed a positive
reaction to MNF116 on the basal and suprabasal cells (Fig.
1C). LL002 stained the basal and immediately suprabasal cells
in cases 2 to 4 (Fig. 1D).
Only basal cells were positive to LL002 in cases 5 to 8 (Fig.
1E).
Although LL002, which reacts specifically to
CK14, stains only basal cells in the formalin-fixed and paraffin-embedded
sections of normal epidermis, CK14 expression on suprabasal keratinocytes
with the regional inflammation is considered to be caused by a non-specific
response to locally produced hyperproliferative stimuli [4]. Among the
cytokeratins which react to MNF116, CK5 is the most abundant in basal
cells. The positive MNF116 reaction on suprabasal cells in inflammatory
skin diseases is considered to indicate the expression of CK5 which is
a pair cytokeratin of CK14, although cytokeratins 6 and 17 are also expressed
in keratinocyte hyperproliferation [5].
The positive reaction on suprabasal cells in
the present cases demonstrated the change of cytokeratin expression due
to inflammation. Only in case 1, was the reduced staining on suprabasal
cells revealed in the area with blisters, despite a positive reaction
on the suprabasal cells in the surrounding area. This phenomenon demonstrates
the reduced CK5 and CK14 expression, which is caused by the degeneration
of proliferative basal cells in HG. It supports the notion that the degree
of basal cell damage in HG is higher than that in BP. Although four out
of seven BP cases showed a negative reaction to LL002 on suprabasal cells,
this staining pattern was seen in the areas with and without blisters.
We think that the epidermis in these BP cases were not stimulated sufficiently
for CK5 and CK14 expression on suprabasal cells in formalin-fixed and
paraffin-embbeded sections.
REFERENCES
1. Giudice GJ, Emery DJ, Zelickson BD, Anhalt GJ, Liu Z, Diaz LA. Bullous
pemphigoid and herpes gestationis autoantibodies recognize a common non-collagenous
site on the BP180 ectodomain1. J Immunol 1993; 151: 5742-50.
2. Hertz KC, Katz SI, Maize J, Ackerman AB. Herpes gestationis. A clinicopathologic
study. Arch Dermatol 1976; 112: 1543-8.
3. Hirose M, Akiyama T, Ichiki Y, Satoh S, Izumi T, Seishima M, Kitajima
Y. Herpes gestationis: time course of the change in antibody titer after
abortion. Eur J Dermatol 1997; 7: 134-6.
4. Perkins W, Campbell I, Leigh IM, Mac Kie RM. Keratin expression in
normal skin and epidermal neoplasms demonstrated by a panel of monoclonal
antibodies. J Cutan Pathol 1992; 19: 476-82.
5. Leigh IM, Navsaria H, Purkis PE, Mcka IA, Bowden PE, Riddle PN. Keratins
(K16 and K17) as markers of keratinocyte hyperproliferation in psoriasis
in vivo and in vitro. Br J Dermatol 1995; 133: 501-11.
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