Basal cell destruction of herpes gestationis and bullous pemphigoid

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.