Immunoglobulins at the dermal-epidermal junction in lupus erythematosus: ultrastructural investigations

Summary The ultrastructural localization of immunoglobulins bound in vivo in LE skin was investigated by means of an electron microscopic immuno-peroxidase method. Three patients, one with SLE and two with CDLE, were studied. Immunoglobulins were demonstrated in a junctional zone which included the basal lamina and the most superficial layer of the subjacent dermis, one to two micra in width. The immunoglobulins were seen on the lamina, in the ground substance and on the fibrous components of his zone. A coating of collagen fibers by immunoglobulins was observed, as were, occasionally, immunoglobulin deposits in the microfibril-areas of elastic fibers.Immediately below the basal lamina the immunoglobulins formed irregular aggregates of various size. They also extended beyond the lamina and coated the plasma membrane of basal cells. This immunoglobulin coat was consistently found on the half desmosomes.There were no significant differences in the localization patterns of immunoglobulins in SLE and CDLE lesions. In CDLE skin the immunoglobulin positive zone was wider, the deposits were heavier and the irregular immunoglobulin aggregates were larger and more numerous. Reduplications of the basal lamina also exhibited immunoglobulin deposits.It is concluded from various observations that these immunoglobulins are, at least in part, bound to antigenic sites within the junctional zone. It is hypothesized that the immunochemical staining patterns obtained in LE lesions are due both to antibasement membrane zone antibodies specifically bound to antigens in this region and to immune complexes nonspecifically deposited in the tissue.

---

Zusammenfassung Die ultrastrukturelle Lokalisation der in vivo in LE-Läsionen gebundenen Immunglobuline wurde mittels einer elektronenmikroskopischen Immun-Peroxidase-Methode untersucht (1 Patient mit SLE, 2 Patienten mit CDLE). Immunoglobuline wurden in der dermo-epidermalen Junctionszone sowie in einem Bereich, der die Basallamina und einen 1–2 µ breiten, daruntergelegenen Streifen des papillären Bindegewebes umfaßt, nachgewiesen. Die Globuline sind innerhalb dieser Zone an der Basallamina, in der Grundsubstanz und an den Bindegewebsfasern lokalisiert. Kollagenfasern sind von einer Globulinhülle umgeben, elastische Fasern weisen gelegentlich Globulinablagerungen im Bereich ihrer Mikrofibrillen auf.Knapp unterhalb der Basallamina bilden die Immunglobuline unregelmäßige Aggregate unterschiedlicher Größe. Sie erstrecken sich aber auch über die Basallamina hinaus bis an die Plasmamembran der Basalzellen, an deren Oberfläche sie mantelförmige Ablagerungen bilden. Diese Immunglobulinschicht findet sich regelmäßig an der Oberfläche der Halbdesmosomen.Zwischen den Ablagerungen bei SLE und CDLE bestehen keine grundsätzlichen Unterschiede. In CDLE-Läsionen ist die Immunglobulin-positive Zone allerdings breiter, die Ablagerungen sind dichter und die Aggregate zahlreicher und größer. Reduplikationen der Basallamina sind ebenfalls von Immunglobulinen markiert.Es wird aus einer Reihe von Beobachtungen geschlossen, daß diese Immunglobuline, zumindest z.T., an antigene Strukturen in der Junctionszone gebunden sind.Das immunocytochemische Reaktionsmuster von LE-Läsionen kommt offenbar sowohl durch Antikörper gegen die Basalmembran-Region, die an Antigene in der Junctionszone gebunden werden, als auch durch unspezifisch abgelagerte Immunkomplexe zustande.

---

---

Supported, in part, by Fonds zur Förderung der wissenschaftlichen Forschung, Wien, and Schering AG, Berlin.     

The significance of an IgM band at the dermoepidermal junction

We studied 190 patients with an IgM band at the dermo-epidermal junction demonstrated by direct immunofluorescence. In 55% of patients the final diagnosis was lupus erythematosus, 49% discoid lupus erythematosus, and 6% systemic lupus erythematosus. In 45% of patients the presence of an IgM band was associated with a number of other diagnoses. The finding of an IgM band at the dermo-epidermal junction in a cutaneous biopsy is not sufficient evidence to make a diagnosis of lupus erythematosus without supporting clinical, histological and serological evidence.     

The dermoepidermal junction in skin diseases]

Dermatological conditions characterized by dermo-epidermal separation, basal lamina discontinuity, multiplication, and thickness variability, and/or irregularity of the subepidermal space are discribed. Pathological changes of the dermo-epidermal junction are considered to be destructive or reproductive. Both may appear in combination. Destructive processes may be relfected by dermo-epidermal separation. Epidermal cells and/or dermal connective tissue appear degenerated. Thickening of the lamina may occur by reactive hyperproduction or by precipitation of pathological materials. Reproductive processes of the junction originate in the epidermal cells and are reflected in multilayering of the basal lamina. Interruption of the lamina and irregularity of the subepidermal space often precede these phenomena.     

Characterization of the inflammatory infiltrate and expression of endothelial cell adhesion molecules in lupus erythematosus tumidus

Lupus erythematosus tumidus (LET) is a disease with characteristic clinical and histopathologic features that has not always been considered a subset of cutaneous lupus erythematosus (CLE). Although LET was first mentioned in the literature in 1930, it has rarely been documented, and immunohistochemical studies have never been performed. The aim of the present study was to characterize the inflammatory infiltrate and to analyze the expression of endothelial cell adhesion molecules in skin specimens from patients with LET and to compare the results with those from patients with other variants of CLE, such as discoid lupus erythematosus (DLE) and subacute cutaneous lupus erythematosus (SCLE). Cryostat sections of lesional skin specimens from ten patients with LET demonstrated an infiltrate composed of more than 75% CD4+, CD8+, and HLA-DR+ cells. Interestingly, CD45RO+ cells, in contrast to CD45RA+ cells, were the prevailing inflammatory cell population. Compared with skin specimens from patients with DLE and SCLE, the mean expression of CD4+ and CD8+ cells was higher (but not significantly so) in LET, and no differences were observed with the other three antibodies. Furthermore, in contrast to controls, intercellular adhesion molecule-1, vascular adhesion molecule-1, E-selectin, and P-selectin showed the same expression pattern in skin specimens from patients with DLE, SCLE, and LET. In conclusion, the inflammatory infiltrate of LET primarily consists of CD4+/CD8+ lymphocytes. Furthermore, expression of endothelial cell adhesion molecules was equally upregulated in LET compared with the expression in DLE and SCLE, suggesting a similar immunopathomechanism of these subtypes of CLE.     

Vascular changes of chronic lupus erythematosus

Summary Vascular changes in the course of chronic lupus erythematosus were mainly characterized by a large, yet varying degree of proliferation of endothelial cells. In all cases examined the presence of tubular forms similar to paramyxoviruses was noted.The vascular basal membrane was noted to be either widened, segmentally separated or absent in places. Collagen fibres in these cases adhered directly to the endothelial cells.In the nuclei of endothelial cells of the infiltrate, nuclear bodies could be observed. In area surrounding capillaries oval concentrations of fibrilles 80 Å in diameter were noticed.

---

Zusammenfassung Die wesentliche Proliferation des Endothels von verschiedener Intensität ist beim chronischen Lupus erythematodes für die beobachteten Gefäßveränderungen bezeichnend.In allen untersuchten Fällen wurden die paramyxovirusähnlichen tubulären Strukturen aufgewiesen. Die Basalmembran unterlag Veränderungen in Form teilweiser Erweiterung und Zerspaltung oder herdartiger Atrophie. In diesen Fällen liegen die kollagen Fasern unmittelbar an den Endothelien.In den Kernen des Endothels und den Zellinfiltrationen traten oft nuclear bodies auf. In der Umgebung der Capillaren war das Vorhandensein scharf begrenzter, ovaler Fibrillenanhäufungen mit ca. 80 Å Durchmesser bemerkbar.

     

Immunohistochemistry of ultrastructural changes in scarring lupus erythematosus

Background. The various clinical types of lupus erythematosus (LE) show an essentially similar histological picture, and the subsets of LE cannot easily be distinguished by histology alone. However, there is an important clinical difference: lesions of discoid LE (DLE) cause scarring, particularly on the scalp, whereas lesions of subacute and acute LE heal without scarring. The focal thickening of the basement membrane zone (BMZ) in DLE lesions represents an important histopathological finding, and there is little known about the nature of these alterations at the BMZ level. Aim. To investigate BMZ alterations in the basement membrane zone (BMZ) in cutaneous LE (CLE) by immunohistochemistry. Methods. Skin biopsies from 30 patients with CLE [DLE and subacute CLE (SCLE)] and from 10 controls were studied using antibodies to cytokeratin 5, cytokeratin 14, bullous pemphigoid (BP)180, BP230, plectin, laminin 5, collagen IV and collagen VII. Results. There was increased expression of components of the lamina lucida, lamina densa and anchoring fibrils in active DLE, whereas expression was normal in SCLE and control tissues, and in areas of scarring in DLE. In addition, higher expression of the hemidesmosome‐associated antigens (BP230 and plectin) was found in active DLE. The expression of other antigens was similar in all tissues examined. Conclusions. These alterations in the BMZ suggest that the BMZ may react in a different way in active DLE than in SCLE, and that the BMZ may remodel in different ways. These immunohistochemical differences may provide a new method of histological differentiation between the various LE subtypes.     

Coexistence of extensive calcification and membrano-cystic changes in lupus erythematosus panniculitis associated with systemic lupus erythematosus

We report a case of lupus erythematosus panniculitis with long-standing systemic lupus erythematosus. The patient developed widespread calcification and membrano-cystic changes in the subcutaneous tissue. There have been no reports of the coexistence of calcification and membrano-cystic changes in the literature. The mechanism for the coexistence of the calcification and membrano-cystic changes might be due to the degenerative changes in fat cells from local circulatory disturbance.     

Lipomembranous changes associated with systemic lupus erythematosus

Lipomembranous changes are distinctive histopathological findings, which include the presence of cystic cavities lined by crenulated, hyaline membranes in adipose tissue. It is likely that ischaemia is fundamental to the development of these lesions, and that lipomembranes are formed from the products of degenerating fat cell membranes by some unknown mechanism. Such changes may be seen, although rarely, in many types of subcutaneous inflammatory processes. However, an association with systemic lupus erythematosus (SLE) is rare. We report a patient with SLE who had the histological features of lipomembranous changes associated with vasculopathy.     

Unexpected diminished innervation of epidermis and dermoepidermal junction in lichen amyloidosus

Background  Lichen amyloidosus is a localized, chronic, pruritic skin disease characterized by deposition of amyloid in the papillary dermis. The pathogenesis of the pruritus of lichen amyloidosus is largely unknown.
Objectives  To determine any change in the nerve fibre density in lichen amyloidosus lesions as an explanation for itch.
Methods  Using an antibody to protein gene product (PGP) 9.5, the immunohistochemical analysis of the skin biopsies of 30 Hispanic patients with clinicopathologically proven lichen amyloidosus and of 11 healthy Hispanic controls matched for age, sex and site was performed.
Results  Unexpectedly, the mean amount of PGP9.5 stain, a measure for nerve fibre amount, for the healthy controls was higher than the lichen amyloidosus group both in the epidermis ( P  <   0·0019) and dermoepidermal junction ( P  <   0·0064). No change was observed in the papillary dermis. Furthermore, the proportion of area covered by PGP9.5 showed a significant decrease in the epidermis ( P  <   0·0024) and dermoepidermal junction ( P  <   0·0075) in lichen amyloidosus compared with healthy controls. Age, gender and body site were found not to be influencing factors in nerve fibre amounts in lichen amyloidosus samples.
Conclusions  We speculate that the severe pruritus observed in lichen amyloidosus might be the result of the hypersensitivity of the remaining nerve fibres as a response to an unexplained neurodegeneration of the absent nerve fibres.     

Different patterns of soluble adhesion molecules in systemic and cutaneous lupus erythematosus

Abstract Circulating isoforms of cellular adhesion molecules (CAMs) have been described recently, and elevated levels of certain sCAMs have been reported in various inflammatory diseases such as systemic lupus erythematosus (SLE). There are previously no reports on sCAMs in cutaneous LE. Sera from 61 patients with LE: systemic (SLE: n= 24), chronic cutaneous (discoid LE, DLE: n= 19) or subacute cutaneous (SCLE: n= 8), chronic biologically false positive (CBFP) reactors for syphilis (n= 10) and 32 controls were examined for sICAM-1, sVCAM-l and sE-Se-lectin with specific ELISA kits. Protocol forms were reviewed. We found significantly elevated levels of sE-Selectin in patients with DLE and widespread cutaneous symptoms, and a correlation between active cutaneous disease as well as polymorphous light eruption (PLE) and elevated levels of sE-Selectin. In contrast, patients with systemic LE did not have elevated levels of sE-Selectin, but in concordance with earlier reports, sICAM-1 and sVCAM-l levels were elevated compared to controls in SLE. as well as in SCLE patients, which has not been reported previously. Since activated endothelial cells are the only source for E-Selcetin, the elevated sE-Selectin level in patients with widespread and active cutaneous disease suggests a more important role for endothelial cells in the pathogenesis of cutaneous LE than previously assumed.     

PUVA-induced blisters, complement deposition, and damage to the dermoepidermal junction

We followed the course of 56 patients receiving psoralen plus long-wave ultraviolet light (PUVA) therapy. Nonhemorrhagic blisters developed on clinically normal skin on the limbs of seven patients. Seeming to be related to friction and trauma, the blisters form as a result of damage to the basal and suprabasal layers. Perilesional skin specimens from all blistered patients contained granular deposits of C3 at the dermoepidermal junction, around the upper dermal blood vessels, or at both sites. The average time for initiation and complete formation of suction blisters was measured in 51 patients at different stages during the course of PUVA treatment. Blister separation was in the lamina lucida, with the pemphigoid antigen in the roof while the blister floor contained the lamina densa, laminin, and type IV collagen. This impaired dermoepidermal adhesion was a general phenomenon that occurred in all PUVA-treated patients. The mechanism remains to be determined.