Estimation of (IgA) anti-gliadin, anti-endomysium and tissue transglutaminase in the serum of patients with psoriasis

Studies have indicated an association between psoriasis and coeliac disease (CD), an immune-mediated gluten-dependent enteropathy; however, the precise relationship between psoriasis and CD remains controversial. We aimed to assess the prevalence of the CD-associated IgA antibodies antigliadin antibody (AGA), tissue transglutaminase (tTG) and antiendomysium antibody (EMA) in patients with psoriasis. In total, 41 patients with psoriasis and 41 healthy controls were enrolled in this study. Blood samples were taken from all participants, and screened for AGA, tTG and EMA. We found a significantly higher level of AGA in patients with psoriasis than in controls, but levels of tTG and EMA were not significant. There was also a significantly higher prevalence of AGA, tTG and EMA in the patient group (34.1%, 34.1% and 14.6%, respectively) than in the control group (2.4%, 22% and 4.9%, respectively). We conclude that the significantly high prevalence of AGA antibodies in patients with psoriasis supports the possibility of a link between psoriasis and gluten-sensitive enteropathies, especially CD.     

IgA class antibodies in dermatitis herpetiformis: reaction with tissue antigens

The mechanism for deposition of IgA in dermatitis herpetiformis (DH) remains unclear. To test the hypothesis that a circulating IgA class antibody in DH patients binds to constituents of normal human skin, we employed the highly sensitive methods of immunoblotting and indirect immunofluorescence. Sera from 64 DH patients, 67 randomly selected normal control subjects, 29 histocompatibility locus antigen (HLA) B8/DR3/DQw2 controls, and 12 psoriatic patients were tested for IgA binding to various substrates, including dermal and epidermal extracts, fibroblast and keratinocyte supernatants, monkey esophagus sections, and whole and saline-split normal human skin sections. Significant differences observed among the groups in the frequency of detectable IgA antibodies reacting with various substrates were as follows: 1) IgA antibodies in 30% of both DH and HLA B8/DR3/DQw2 sera bound to a 60-Kd protein in dermal extracts (p less than 0.25 versus non-HLA matched controls); 2) IgA antiendomysial antibodies were present in 38% of DH patients (predominantly those not on gluten-free diets), whereas both normal control groups had frequencies of 5-10% (p less than 0.025); 3) there was more nonspecific IgA antibody-binding to dermal, epidermal, and bovine proteins in DH and HLA control sera than in normal sera; and 4) IgA antibodies directed against the basement membrane were present with an increased frequency of 25% in both DH and HLA B8/DR3/DQw2 sera (p less than 0.1 versus non-HLA matched controls). Therefore, these results do not support the hypothesis that there is an unique antigen within normal human skin to which IgA antibodies from DH sera bind.     

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.     

IgA antiendomysial antibodies in dermatitis herpetiformis

Sera from 24 patients with dermatitis herpetiformis and 80 control subjects (patients with other bullous diseases, nonbullous dermatoses, and noncutaneous diseases) were studied to determine the usefulness of assay for IgA antiendomysial antibodies (IgA-EMA) in the diagnosis of dermatitis herpetiformis. The overall sensitivity of IgA-EMA for the diagnosis of dermatitis herpetiformis was 79% and the specificity was 96%. When the three patients with dermatitis herpetiformis who were faithfully following gluten-free diets were excluded, the sensitivity was 90% and the specificity was 96%. No patient in the bullous disease control group (including patients with linear IgA bullous dermatosis) had circulating IgA-EMA. One patient, who did not have direct immunofluorescence evidence for dermatitis herpetiformis but had IgA nephropathy, had a positive IgA-EMA result, an interesting association in light of the rare reports of dermatitis herpetiformis in patients with IgA nephropathy and IgA antigliadin antibodies associated with IgA nephropathy. Although direct immunofluorescence testing of skin biopsy specimens remains the most definitive diagnostic test for dermatitis herpetiformis, indirect immunofluorescence assay of serum for IgA-EMA is a minimally invasive study with a high sensitivity and specificity for dermatitis herpetiformis.     

Autoantigens for IgA anti-intercellular antibodies of intercellular IgA vesiculopustular dermatosis

A new disease characterized by the presence of in vivo bound and/or circulating IgA anti-intercellular (IC) antibodies has recently been identified. We propose the term intercellular IgA vesiculopustular dermatosis (IAVPD) for this entity, which seems to be divided clinicopathologically into at least two distinct subtypes: intraepidermal neutrophilic IgA dermatosis (IEN type) and subcorneal pustular dermatosis-like cases (SPD type). Using immunoblot technique, we examined the antigen substances for the IgA anti-IC antibodies in the sera from one Japanese patient with IEN type of IAVPD and three Japanese patients with SPD type. A serum from a patient with IEN type reacted exclusively with a 120-kD protein in both the normal human skin extract and the bovine desmosome sample. Sera from three patients with SPD type reacted specifically with a doublet of 115-kD and 105-kD proteins, which appeared to be identical to desmocollins I and II, well known desmosomal core proteins, in the bovine desmosome sample. IgA antibody from our patients with IAVPD bound to neither pemphigus vulgaris antigen nor pemphigus foliaceus antigen. From these results, we suggest that IAVPD is different from pemphigus and is heterogeneous in terms of the antigens to which IgA autoantibodies bind.     

IgA antineutrophil cytoplasmic antibodies in cutaneous vasculitis

Background  Antineutrophil cytoplasmic antibodies (ANCA) of the IgA isotype have, for the most part, been detected in patients with Henoch–Schönlein purpura (HSP) or inflammatory bowel disease. Objectives  We have evaluated the prevalence of IgA ANCA in a series of patients with different causes of cutaneous vasculitis. Methods  Forty consecutive patients with histologically proven leucocytoclastic vasculitis were included in the study: 18 had systemic vasculitis as well as cutaneous lesions, 10 of whom were diagnosed as having HSP, and 22 had only cutaneous vasculitis (with no identified cause in 10 cases). IgA ANCA were sought by indirect immunofluorescence using ethanol-fixed human neutrophil preparations as the substrate. Results  IgA ANCA were detected in six of 40 patients (15%) (one each with HSP, ulcerative colitis, Sjögren's syndrome, hypergammaglobulinaemia associated with Castelman's disease, erythema elevatum diutinum and bacterial endocarditis). Three of these patients also had IgG ANCA whose target antigen remained unidentified. Conclusions  IgA ANCA are rarely observed in HSP (10%) and can be detected in a wide variety of other cutaneous vasculitides.     

IgA antibodies recognizing LABD97 are predominantly IgA1 subclass.

Linear IgA bullous dermatosis is a rare acquired subepidermal blistering disease of the skin. A recognized antigen in linear IgA bullous dermatosis is a 97-kDa basement membrane zone protein termed LABD97. Previous studies, using immunofluorescent techniques, have suggested that the IgA response is restricted to the IgA1 subclass. We studied the IgA antibody subclasses in the sera of 6 patients that contained circulating IgA antibodies reactive with LABD97. The methods used included direct and indirect immunofluorescence and Western immunoblot. All patients tested had IgA1 anti-LABD97 antibodies detected by all 3 methods. Two patients had IgA2 antibodies detected by direct immunofluorescence. Three patients had IgA2 antibodies on indirect immunofluorescence. Two of these also had anti-LABD97 IgA2 antibodies and 1 had secretory component containing anti-LABD IgA antibodies on Western immunoblot. We conclude that the predominant IgA antibody subclass reactive with LABD97 in LABD is IgA1, although the IgA2 subclass may be involved in some cases.     

Elevation of IgA anti-epidermal transglutaminase antibodies in dermatitis herpetiformis

Background  Dermatitis herpetiformis (DH) is a papulovesicular eruption caused by ingestion of gluten. It is characterized by the deposition of IgA in the dermal papillae. IgA antibodies directed at tissue transglutaminase (TG2) are elevated in gluten-sensitive diseases including DH and coeliac disease (CD). More recently, antibodies directed at epidermal transglutaminase (TG3) were identified in patients with DH, and this may be the dominant autoantigen in this disease.
Objectives  To measure IgA antibodies to TG3 and TG2 in patients with DH and CD, and control populations.
Methods  Serum IgA antibodies against TG2 and TG3 were measured from adults with DH, adults and children with CD, patients with psoriasis, adult Red Cross blood donors, and paediatric controls.
Results  Patients with DH and CD had elevated levels of IgA anti-TG2 antibodies compared with control populations. The levels in the patients with DH and adults with CD were similar. IgA anti-TG2 antibodies were higher in the children with CD compared with adults with DH and CD, and with control populations. Patients with DH and adults with CD had elevated levels of IgA anti-TG3 antibodies compared with children with CD and control populations. There was a trend towards higher levels in the patients with DH compared with adults with CD.
Conclusions  IgA antibodies to TG3 are elevated in patients with DH and adults with CD. The progressive expansion of the epitope-binding profile of IgA antitransglutaminase antibodies in patients with CD may explain the development of DH in patients with undiagnosed CD during their adult life.     

Circulating IgA anti-basement membrane zone antibodies in dermatitis herpetiformis.

Criculating anti-basement membrane zone antibodies of the IgA class were detected in the sera of 2 or 6 dermatitis herpetiformis (DH) patients who had linear in-vivo-bound IgA deposits and in 1 of 42 DH patients who had granular vivo-bound IgA deposits. In the former 2 patients the circulating antibodies were localized ultrastructurally to the identical site where the in vivo-bound antibodies were localized and were bound by antigens in either the lamina lucida or the subbasal lamina anchoring fibril area of the basement membrane zone of normal human skin.     

Linear IgA disease with IgA antibodies directed against 200- and 280-kDa epidermal antigens

We report an 80-year-old man with the lamina lucida type of linear IgA disease, with IgA autoantibodies reactive with 200-kDa and 280-kDa epidermal proteins. The patient presented with widespread bullous lesions on his trunk and extremities without mucosal involvement. Histopathology of lesional skin showed a subepidermal blister with papillary microabscesses of neutrophils and a few eosinophils. Direct immunofluorescence microscopy of perilesional skin showed linear deposits of IgA and C3 at the basement membrane zone. The patient's serum contained IgA autoantibodies that bound exclusively to the epidermal side of 1 mol L-1 NaCl split skin as determined by indirect immunofluorescence microscopy. Circulating IgA autoantibodies to 200- and 280-kDa antigens were detected in the patient's serum by immunoblot analysis using extracts from normal human epidermis and human epidermal keratinocytes. These two antibodies, eluted from individual nitrocellulose membranes, reacted with the epidermal side of 1 mol L-1 NaCl split skin on indirect immunofluorescence microscopy, and bound to hemidesmosomes as determined by immunoperoxidase electron microscopy. This observation suggests the presence of hitherto uncharacterized 200- and 280-kDa hemidesmosomal proteins distinct from BPAG1, BPAG2 and beta4 integrin as target antigens in linear IgA disease.     

Variation in the deposition of the antibodies at different anatomical sites in linear IgA disease of adults and chronic bullous disease of childhood

The diagnosis of linear IgA disease of adults (LAD) and chronic bullous disease of childhood (CBDC) relies upon finding a linear band of IgA at the basement membrane zone on direct immunofluorescence. This study examines the regional variation in antigen expression in the skin of affected individuals. Direct immunofluorescence was performed on biopsies from four different sites in 17 patients with these diseases. In two patients a biopsy from the volar surface of the forearm was negative, but other sites were positive; in the remaining patients there was no variation in antibody expression with site. It is therefore recommended that, if a single diagnostic biopsy is to be taken, the volar surface of the forearm is avoided.     

Drug-induced linear IgA disease with antibodies to collagen VII

Linear IgA disease (LAD) is characterized by circulating and tissue-bound IgA antibodies against heterogeneous antigens in the cutaneous basement membrane zone. In most cases the cause is unknown, but a minority of cases has been drug induced. We report a 76-year-old man who developed an acute blistering eruption following high-dose penicillin treatment for pneumococcal septicaemia. Indirect immunofluorescence demonstrated dermal binding IgA antibodies, and Western blotting of serum showed reactivity with a 250 kDa dermal antigen corresponding to collagen VII of anchoring fibrils. Indirect immunoelectron microscopy showed antibody labelling in the lamina densa and sublamina densa zone. This is one of the few cases of drug-induced LAD in which the target antigen profile has been characterized, and the first in which the antigen has been shown to correspond to collagen VII.     

A case of linear IgA disease in a child with IgA and IgG circulating antibodies directed to BPAg2

A 7-year-old Caucasian girl had multiple bullae on the trunk, upper and lower limbs (Fig. 1a,b) for 10 days. The lesions were large, tense, and asymptomatic, and mucosae were not involved. Laboratory findings were all normal. Histopathology revealed a subepidermal blister containing numerous neutrophils, eosinophils, and fibrin. Direct immunofluorescence of perilesional skin disclosed linear deposition of IgA and slight linear deposits of IgM at the basement membrane zone (Fig. 2). Indirect immunofluorescence on monkey esophagus and on human salt-split skin was negative. Immunoblot assay (IB), performed with an epidermal extract, revealed IgA and IgG antibodies directed to BPAg2 antigen (Fig. 3), while it was negative when performed on dermal extract. Enzyme-linked immunosorbent serologic assay using a commercial kit (MBL, Naka-Ku Nagoya, Japan) with the noncollagenous domain (NC16A) of the BPAg2 antigen was negative for both IgA and IgG. A diagnosis of linear IgA disease (LAD) was made and a treatment with dapsone (50 mg/day) and prednisolone (30 mg/day) was initiated. One month later, lesions had cleared.