Tadeusz P. Chorzelski

IgA anti‐endomysium antibody. A new immunological marker of dermatitis herpetiformis and coeliac disease

The recently described IgA anti‐endomysial antibodies (IgA‐EmA) are directed against the intermyofibril substance of the smooth muscle, which may correspond either to a reticulin‐like structure or a surface component of smooth muscle fibrils. These antibodies occurred in about 80% of sera of thirty‐eight patients with dermatitis herpetiformis (DH), in about 70% of twenty‐eight patients with coeliac disease and in about 20% of nine patients with other enteropathies. IgG class anti‐gliadin antibodies (AGA) also occur in each of these diseases. Both antibodies were detected on monkey oesophagus by immunofluorescence. The IgA‐EmA could not be detected in 122 control sera from patients with other gut or skin diseases, including fifteen cases with ulcerative colitis and fifteen cases with linear IgA bullous dermatosis (LABD). The presence and the titre of IgA‐EmA and AGA paralleled the severity of the jejunal changes in patients with coeliac disease.

Scl 70 antibody—a specific marker of systemic sclerosis

Scl 70 antibodies were tested for in 107 patients with systemic sclerosis: 68 with acrosclerosis and 39 with diffuse scleroderma. Anticentromere antibodies (ACA) and other antinuclear antibodies (ANA) were tested for by indirect immunofiuorescence on HEp‐2 cells. Positive results for Scl 70 antibodies were obtained in 77percnt; of cases of diffuse scleroderma and 44percnt; of acrosclerosis. ACA and Scl 70 antibodies were found to be mutually exclusive. If acrosclerosis cases positive for anticentromere antibodies are excluded, the percentage of acrosclerosis cases positive for Scl 70 was 63percnt;. ACA were found to be a marker of a benign, abortive subset of acrosclerosis with almost no cutaneous involvement (CREST), whereas Scl 70 did not discriminate between acrosclerosis and diffuse scleroderma. On HEp‐2 cells Scl 70 positive sera gave a characteristic, fine speckled, almost homogeneous nuclear staining pattern.

IMMUNOSUPPRESSANTS IN THE TREATMENT OF PEMPHIGUS

The results are presented of parenteral treatment with methotrexate (12·5 mg. twice a week) in 19 cases of various forms of pemphigus; small doses of corticosteroids (usually 8–32 mg. daily) were given in addition. Two other cases, both of pemphigus erythematosus, were treated with azathioprine.

Chronic ulcerative stomatitis associated with a specific immunologic marker

Four elderly women with chronic oral ulcerations are described. The lesions are chronic, erosive, or ulcerative; occur on the gingival, buccal, or lingual mucosa; and may occur in the form of desquamative gingivitis. The histopathologic findings are nondiagnostic. The disease is refractory to local and systemic corticosteroids, but treatment with hydroxychloroquine may be effective. Both in vivo binding to the oral mucosa and skin of a stratified epithelium-specific antinuclear antibody and high titers of these antibodies in serum are markers of this disease, which we refer to as chronic ulcerative stomatitis associated with stratified epithelium-specific antinuclear antibody.

Autoimmunity in psoriasis

SummaryThe stratum corneum (SC) antibodies are present in all human sera as seen by indirect immunofluorescent (IF) staining. They appear to bind in vivo to the stratum corneum of psoriatic lesions. They fix complement in vitro in a two step complement IF test system using either anti C4 or anti C3 conjugates as indicators. IF tests with proper controls showed that the SC antigen in psoriatic scales is coated not only with IgG but in a majority of the lesions also with complement. In the present studies in fully developed lesions complement was detectable in 88% of the specimens studied and in about 50% of very fresh linear lesions of unintentional Köbner type. These as well as some previously published observations afford indirect evidence for the participation of SC antibodies and the ensuing fixation of complement in the development of psoriatic lesions.ZusammenfassungAntikörper gegen Stratum corneum (SC) befinden sich in Seren aller Menschen und können mittels der indirekten Immunofluorescenzmethode festgestellt werden. In Psoriasis-Herden scheinen sie in vivo im Stratum corneum fixiert zu sein. Sie fixieren Komplement in vitro, was man durch Komplement-Fixierungs-Tests unter Benutzung von anti C4 oder anti C3 Konjugaten beweisen kann. IF-Teste mit unterschiedlichen Kontrollen haben aufgezeigt, daß Stratum corneum als Antigen in Psoriasis-Läsionen nicht nur von IgG, sondern in der Mehrheit der Veränderungen auch von Komplement umgeben ist. In völlig entwickelten Läsionen wurde das Komplement in 88% der Biopsien festgestellt, weniger häufig — in ungefähr 50% — in sehr frühen linearen Hautveränderungen vom Typ des zufälligen Köbnerschen Phänomens. Diese und frühere Beobachtungen erbrigen einen indirekten Beweis, daß Antikörper SC an der Entstehung der Psoriasisherde teilnehmen, und die Komplementfixierung hier von Bedeutung sein könnte.

THE SCOPE AND LIMITATIONS OF THE IMMITNOFLUORESCENCE METHOD IN THE DIAGNOSIS OF LUPUS ERYTHEMATOSUS

Immunofluorescence studies were made in 51 cases of rosacea and 8 cases of telangiectasia of various origins. Immunoglobulins were found—as in LE—at the epidermal‐dermal junction in 35 of the cases of rosacea and in all telangiectasias, irrespective of their origin. The need for great caution in the interpretation of biopsy studies of facial lesions is stressed. Detection of immunoglobulins at the epidermal‐dermal junction in clinically normal skin is, however, very important for the diagnosis of SLE

IgA anti-endomysial antibodies in dermatitis herpetiformis: correlation with jejunal morphology, gluten-free diet and anti-gliadin antibodies

Circulating IgA‐class anti‐endomysium antibodies (EmA) can be detected by indirect immunofiuorescence on monkey oesophagus sections. We found EmA in 22 (76%) of 29 patients with dermatitis herpetiformis (DH) on a normal, gluten‐containing diet. The highest frequency (100%) of EmA was observed in patients with sub‐total villous atrophy. IgA‐class antigliadin antibodies (AGA) were found using an ELISA method in 59% of 29 DH patients and in 86% of those with sub‐total villous atrophy. There was a significant correlation between EmA litres and AGA levels in individual patients.

Linear IgA bullous dermatosis of adults.

The skin disorder designated as linear IgA bullous dermatosis (LABD), identified in 1979 (l), had been for many years a matter of controversy. This controversy was due mainly to its clinical diversity, as some cases closely resemble dermatitis herpetiformis (DH), some cases are indistinguishable from bullous pemphigoid (BP), and still other cases combine features of both (2). No wonder that some authors considered this disease as DH or its variety (3 6), others as BP (7,8), and yet others as intermediate or mixed forms of DH and BP (2,9). In support of the relationship with DH were the skin immune deposits of immunoglobulin A (IgA) class and, as a rule, a dramatic response to sulfones. Supporting the relationship with BP were the linear pattern of IgA deposits along the basement membrane zone (BMZ) and, occasionally, the concomitant presence of complement in the same distribution (1,2,9). Furthermore, at least in some cases, the ultrastructural depositions of IgA, in the lamina lucida, similar to that in BP, suggested some relationship between LABD and BP (10 12). In a proportion of cases of LABD, the linear IgA deposits are found below the basal lamina (12-14) or in both locations (6,11,12,15). The main difference from BP is the IgA-class skin deposits, papillary microabscesses in the histology, and, as a rule, a good response to sulfones. The most important reason for separation of LABD from DH is that LABD is not associated with gluten-sensitive enteropathy and, as could be expected, a glutenfree diet is not effective treatment for LABD (16). Recognition of LABD as a distinct entity, despite the clear-cut differences from DH and BP, took a long time until more data on immunoelectron microscopy, serology, genetics,

Sensitivity and specificity of IgA-class antiendomysial antibodies for dermatitis herpetiformis and findings relevant to their pathogenic significance

The specificity and sensitivity of the recently reported IgA-class antiendomysial antibody test for gluten-sensitive enteropathy were evaluated in four double-blind studies involving the sera of fifty-seven patients with dermatitis herpetiformis who were not on a gluten-free diet and ninety-seven assorted control sera. The control sera provided by the four centers included the sera of nineteen patients with dermatitis herpetiformis and two with celiac disease who were on a gluten-free diet, the sera of five normal subjects with human lymphocyte antigens (B8 locus), the sera of thirteen patients with linear IgA bullous dermatosis, and fifty-eight other control sera, mostly from patients with other bullous diseases and other dermatoses. The frequency of IgA antiendomysial antibody in these coded studies was zero of ninety-seven control sera and thirty-four of fifty-seven sera (60%) from patients with dermatitis herpetiformis who were not on a gluten-free diet. The pathogenic role of IgA antiendomysial antibodies in dermatitis herpetiformis and celiac disease is suggested not only by their high degree of disease sensitivity and specificity but also by their formation in response to gluten challenge, their appearance before gut changes, and the in vitro binding of gliadin to the antiendomysial antibody antigen sites. These and other findings in this study and in the literature suggest that gluten-sensitive enteropathy is immunologically mediated and that IgA antiendomysial antibodies play a significant pathogenetic role.

Studies on etiologic factors in pemphigus.

A survey of 234 cases of pemphigus yielded three observations which suggest that different forms of pemphigus may have different etiologies.