Ultrastructural binding sites of endomysium antibodies from sera of patients with dermatitis herpetiformis and coeliac disease.

The ultrastructural binding sites of endomysium antibodies, specific serological markers of gluten sensitive enteropathy, were investigated in the rabbit oesophagus using the immunogold technique. Endomysium antibodies from sera of patients with dermatitis herpetiformis and with coeliac disease bound in an identical manner in a non-fibrillar material closely associated with fine collagenous-reticulin fibrils and also with similar fibrils connecting smooth muscle cells and elastic tissue in the endomysial connective tissue. These observations suggest that IgA antibodies in sera from patients with dermatitis herpetiformis and coeliac disease recognise a common antigen in an amorphous component associated with the reticular connective tissue of oesophageal lamina muscularis mucosae and thus confirm the probable identity of IgA class endomysium and jejunal antibodies.     

In vivo targeting of intestinal and extraintestinal transglutaminase 2 by coeliac autoantibodies

BACKGROUND: IgA class serum autoantibodies against type 2 (tissue) transglutaminase (TG2) bind to both intestinal and extraintestinal normal tissue sections in vitro, eliciting endomysial, reticulin, and jejunal antibody reactions. It is not known whether similar binding also occurs in coeliac patients in vivo, and may thereby contribute to disease manifestations. AIMS: To investigate intestinal and extraintestinal coeliac tissues for the presence of in vivo bound TG2 specific IgA and its relation to small intestinal mucosal atrophy. PATIENTS: We investigated jejunal samples with normal villous morphology from 10 patients with developing coeliac disease who subsequently progressed to a flat lesion, from 11 patients with dermatitis herpetiformis, and from 12 non-coeliac controls. Six extrajejunal biopsy samples (liver, lymph node, muscle, appendix), obtained based on independent clinical indications from patients with active coeliac disease, were also studied. METHODS: Double colour immunofluorescent studies for in situ IgA, TG2, and laminin were performed. IgA was eluted from tissue sections and tested for TG2 specificity by enzyme linked immunosorbent assay and indirect immunofluorescence. RESULTS: IgA (in one IgA deficient case IgG) deposition on extracellularly located TG2 was detected in jejunal and extrajejunal specimens of all coeliac patients, and also in seven of 11 dermatitis herpetiformis patients, of whom two had no circulating endomysial antibodies. IgA eluted from extraintestinal coeliac tissues was targeted against TG2. CONCLUSIONS: Coeliac IgA targets jejunal TG2 early in disease development even when endomysial antibodies are not present in the circulation. Extraintestinal target sites of coeliac IgA further indicate that humoral immunity may have a pathogenetic role.     

Endomysium antibodies in coeliac disease: an improved method.

The ultra structural binding sites of endomysium antibodies have been studied on human umbilical cord tissue. The sensitivity and specificity of IgA endomysium antibodies were compared with recently described methods using basement membrane of smooth muscle of monkey oesophagus. Thirty adults affected by coeliac disease (10 in remission) and 75 healthy adult controls with normal intestinal mucosa (35 false antigliadin positive) were investigated. Sensitivity and correlation of endomysium antibodies with total villous atrophy in untreated coeliac disease patients were 100% on the human umbilical cord smooth muscles, and only 90% on the muscular layer of primate oesophagus. Indirect immunofluorescence was superior to peroxidase staining in detecting these IgA antibodies. The easy availability and enhanced testing sensitivity of the umbilical cord is an advance towards a better diagnostic tool for coeliac disease.     

Missing endomysial and reticulin binding of coeliac antibodies in transglutaminase 2 knockout tissues

BACKGROUND: Autoantibodies against transglutaminase 2 (TG2) are thought to be responsible for the endomysial (EMA), reticulin (ARA), and jejunal antibody (JEA) tissue binding of serum samples from coeliac patients but the exclusive role of TG2 in these staining patterns has not yet been established. AIMS: To evaluate whether antigens other than TG2 contribute to EMA/ARA/JEA reactions. PATIENTS: Serum samples from 61 EMA/ARA/JEA positive untreated patients with coeliac disease, 40 dermatitis herpetiformis patients, and 34 EMA/ARA/JEA negative non-coeliac controls were tested. METHODS: TG2 knockout (TG2-/-) and wild-type mouse oesophagus, jejunum, liver, and kidney sections, and TG2-/- sections coated with human recombinant TG2 were used as substrates in single and double immunofluorescent studies for patient IgA binding and tissue localisation of TG2, fibronectin, actin, and calreticulin. RESULTS: None of the patient serum samples elicited EMA, ARA, or JEA binding in TG2-/- morphologically normal tissues. In contrast, 96 of 101 gluten sensitive patient samples (95%) reacted with wild-type mouse tissues and all 101 reacted in EMA/ARA/JEA patterns with TG2-/- mouse tissues coated with human TG2. Serum IgA binding to TG2-/- smooth muscle cells was observed in low titres in 31.1%, 27.5%, and 20.5%, and to TG2-/- epithelium in 26.3%, 5.0%, and 8.8% of coeliac, dermatitis herpetiformis, and control samples, respectively. These positivities partly colocalised with actin and calreticulin but not with TG2 or fibronectin. CONCLUSIONS: EMA/ARA/JEA antibody binding patterns are exclusively TG2 dependent both in coeliac and dermatitis herpetiformis patients. Actin antibodies are responsible for some positivities which are not part of the EMA/ARA/JEA reactions.     

RETICULIN ANTIBODY IN CHILDREN WITH MALABSORPTION

40 children with coeliac disease were retrospectively studied for reticulin antibody by indirect immunofluorescence. Prior to gluten withdrawal 27 (68%) had antibody in their sera. In some cases antibody titre fluctuated according to gluten withdrawal and provocation. In 20 cases of malabsorption syndrome with cow's milk intolerance, histologically and clinically indistinguishable from coeliac disease, reticulin antibody was not detected. When positive, the reticulin-antibody test should be of clinical value in differential diagnosis. 2 of the reticulin-antibody-positive cases of coeliac disease lacked IgA in their sera. The antibody was found in 4 out of 23 children lacking IgA but with normal jejunal structure.     

Dermatitis herpetiformis: diagnosis, diet and demography

We describe a long term study of 76 patients with dermatitis herpetiformis. Unlike patients with coeliac disease, where the peak incidence was during the first and fourth decades, no dermatitis herpetiformis patients presented in the first decade; also, there was a male preponderance in dermatitis herpetiformis which contrasts with the excess of females in coeliac disease. The apparent prevalence of dermatitis herpetiformis was 11 per 100 000 in our population; approximately one fifth of that of coeliac disease. Jejunal villous atrophy was present in 78% of our dermatitis herpetiformis patients, and a single jejunal biopsy was as effective at detecting this as the multiple biopsy technique. A majority of patients were able to stop, or radically reduce their dapsone or sulphapyridine treatment after the institution of a gluten free diet. Spontaneous remission of the skin lesion occurred in only two patients not receiving a gluten free diet. Gastric parietal or thyroid antibodies were detected in 38% of patients, and three cases of thyroid disease and two cases of pernicious anaemia were detected. Lymphoma developed in two patients, one being intestinal in origin. We conclude that a gluten free diet is of therapeutic benefit in dermatitis herpetiformis and that spontaneous remission is uncommon in those not on a diet. Despite patchiness of the enteropathy, a single jejunal biopsy is quite adequate to diagnose the presence of upper intestinal villous atrophy.     

Antibodies to recombinant human tissue-transglutaminase in coeliac disease: Diagnostic effectiveness and decline pattern after gluten-free diet

BACKGROUND/AIMS: To assess the sensitivity and specificity of IgA and IgG tissue-transglutaminase antibodies assay, the pattern of antibody decline after gluten withdrawal and their modifications with reference to dietary compliance. SUBJECTS: We studied sera from 143 untreated coeliac children and adolescents (8.8+/-6.1 years), 212 sera from 97 of those patients after gluten withdrawal, and 64 control subjects with non-coeliac intestinal disorders (6.8+/-4.8 years). METHODS: Samples were tested for IgA and IgG class tissue-transglutaminase antibodies by radiobinding assay, using human-derived tissue-transglutaminase, and for IgA anti-endomysium antibodies by indirect immunofluorescence on monkey oesophagus. RESULTS: Untreated coeliac patients had significantly higher titres of IgA and IgG tissue-transglutaminase antibodies than controls (p<0.00001); the diagnostic sensitivity was 95.8% and 99.3%, respectively, and the specificity was 95.3%. Three patients with selective IgA deficiency were positive for IgG tissue-transglutaminase antibodies. The concordance rate between IgA tissue-transglutaminase antibodies and anti-endomysium antibodies was 98.1%. Patients on gluten-free diet showed a significant decrease in IgA and IgG tissue-transglutaminase antibodies with respect to untreated patients (p<0.0001). Tissue-transglutaminase was more sensible than anti-endomysium antibodies to detect small amounts of gluten intake when the compliance was poor. CONCLUSIONS: The recombinant human tissue-transglutaminase antibodies assay is a highly sensitive and specific test for diagnosis of coeliac disease, and it is useful in monitoring the compliance to gluten-free diet.     

Antibodies to gliadin in adult coeliac disease and dermatitis herpetiformis

Antibodies to gliadin, searched for by indirect immunofluorescence and a micro-ELISA, were detected in 16 (64%) of 25 sera from patients with adult coeliac disease and in 13 (45%) of 29 with dermatitis herpetiformis. Although the sensitivity of the two tests was relatively low in the whole groups, it increased when only cases with severe jejunum abnormalities were considered (93% for coeliac disease and 81% for dermatitis herpetiformis). A significant correlation was found between antigliadin antibodies and the severity of jejunum damage in both diseases. Moreover, most coeliac and dermatitis herpetiformis patients with antigliadin antibodies were on normal diet. The specificity of the tests was 100% for the immunofluorescence and fairly good for the micro-ELISA, as only 5 (11%) of the 46 disease control patients (Crohn's disease, ulcerative colitis) were positive for antigliadin antibodies. R1-reticulin antibody test was equally specific but less sensitive in both groups. We conclude that antigliadin antibodies are useful in the diagnosis of patients with active adult coeliac disease and dermatitis herpetiformis with gluten-sensitive enteropathy. Moreover, the two tests make it possible to monitor the compliance to gluten-free diet in both diseases.     

Wheat starch-containing gluten-free flour products in the treatment of coeliac disease and dermatitis herpetiformis. A long-term follow-up study

BACKGROUND: We investigated whether wheat starch-based gluten-free products are safe in the treatment of gluten intolerance. METHODS: The study involved 41 children and adults with coeliac disease and 11 adults with dermatitis herpetiformis adhering to a gluten-free diet for 8 years on average. Thirty-five newly diagnosed coeliac patients at diagnosis and 6 to 24 months after the start of a gluten-free diet and 27 non-coeliac patients with dyspepsia were investigated for comparison. Daily dietary gluten and wheat starch intake were calculated. Small-bowel mucosal villous architecture, CD3+, alphabeta+, and gammadelta+ intraepithelial lymphocytes, mucosal HLA-DR expression, and serum endomysial, reticulin, and gliadin antibodies were investigated. RESULTS: Forty of 52 long-term-treated patients adhered to a strict wheat starch-based diet and 6 to a strict naturally gluten-free diet; 6 patients had dietary lapses. In the 46 patients on a strict diet the villous architecture, enterocyte height, and density of alphabeta+ intraepithelial lymphocytes were similar to those in non-coeliac subjects and better than in short-term-treated coeliac patients. The density of gammadelta(+)cells was higher, but they seemed to decrease over time with the gluten-free diet. Wheat starch-based gluten-free flour products did not cause aberrant upregulation of mucosal HLA-DR. The mucosal integrity was not dependent on the daily intake of wheat starch in all patients on a strict diet, whereas two of the six patients with dietary lapses had villous atrophy and positive serology. CONCLUSION: Wheat starch-based gluten-free flour products were not harmful in the treatment of coeliac disease and dermatitis herpetiformis.     

Fc receptor function and circulating immune complexes in gluten sensitive enteropathy--possible significance of serum IgA.

The capacity to clear IgG containing immune complexes from the circulation was studied in patients with coeliac disease (n = 13), dermatitis herpetiformis (n = 8), and coeliac disease with concomitant serum IgA deficiency (n = 4). A small group of patients with active ulcerative colitis (n = 4) was included as a bowel disease control group. Clearance was estimated by measuring the disappearance rate of a bolus dose of intravenously injected IgG coated autologous erythrocytes. The mean T1/2 of clearance was prolonged in both coeliac disease (86 (24) minutes) and dermatitis herpetiformis (111 (35) minutes), compared with healthy subjects (20 (5) minutes) and coeliac patients with concomitant serum IgA deficiency (T1/2 = 17 (6) minutes). Patients with ulcerative colitis had a prolonged clearance, with a T1/2 of 195 (63) minutes. Values of circulating immune complexes were measured by four assays; C1q binding and C3, IgG, and IgA containing immune complexes. C1q binding immune complexes were detected only in IgA deficient gluten sensitive enteropathy. Patients with coeliac disease and dermatitis herpetiformis had higher values of C3, IgG, and IgA containing immune complexes than control subjects and serum IgA deficient patients with coeliac disease. The clearance rate was inversely correlated to the amount of immune complexes for the subgroups of gluten sensitive enteropathy.     

3 The humoral immune system in coeliac disease

IgA is transported into intestinal secretions to perform exclusion of luminal antigens. The prerequisites are antigen sampling by the Peyer's patch M cells, antigen processing by antigen-presenting cells, and presentation of antigenic peptides by HLA class II molecules to immunocompetent T cells. The basis for intestinal immunity is the maturation cycle of specifically primed T and B cells from the gut-associated lymphoid tissue via mesenteric lymph nodes and peripheral blood back to the intestinal lamina propria. In coeliac disease, patients are sensitized against gluten and serum gliadin antibodies are often detected. Gliadin antibodies are also found in other gastrointestinal diseases, other disorders and in healthy individuals not carrying the coeliac disease-specific DQA/DQB alleles. On the other hand, serum reticulin and endomysium autoantibodies are both sensitive and highly disease-specific. Positivity in patients with normal jejunal morphology indicates latency of coeliac disease. These tissue autoantibodies are directed against fibroblast-derived extracellular matrix proteins. The immune system is involved in the amplification and perpetuation of the abnormalities of the intestinal mucosa in coeliac disease. The role of antibody in the pathogenesis remains unknown. The author hypothesizes gluten-triggered autoimmune mechanism to be operative.     

HLA association with dermatitis herpetiformis is accounted for by a cis or transassociated DQ heterodimer.

HLA-DR, DQ, and DP restriction fragment genotyping was undertaken in 23 dermatitis herpetiformis patients and 53 healthy control subjects. HLA-DQw2 was present in 100% of patients with dermatitis herpetiformis (23 of 23) versus 40% of control subjects (21 of 53). Significant secondary associations occurred with HLA-DR3 (91% of patients versus 28% of control subjects) and DPw1 (39% of patients versus 11% of control subjects). Dermatitis herpetiformis and coeliac disease thus share an identical HLA class II association. It is likely that HLA class II genes directly influence the immune responses leading to mucosal damage in both diseases. The strongest candidate for disease susceptibility to dermatitis herpetiformis is DQw2. The HLA molecule most likely to be involved in coeliac disease is a specific DQ alpha/DQ beta heterodimer, encoded in cis arrangement in DR3 haplotypes or in trans arrangement in a DR5, 7 genotype. Our data on dermatitis herpetiformis patients fits this model perfectly. All these patients are capable of expressing this molecule, which may be responsible for the gluten sensitive enteropathy seen in a subgroup of patients with dermatitis herpetiformis and coeliac disease.     

Elevation of IgG antibodies against tissue transglutaminase as a diagnostic tool for coeliac disease in selective IgA deficiency

BACKGROUND: IgA serum autoantibodies against tissue transglutaminase (tTG) have an established diagnostic value in coeliac disease, and high efficacy tests are widely available for their detection. However, serological evaluation of IgA deficient subjects is still difficult. AIMS: To evaluate the diagnostic potential of IgG class anti-tTG autoantibodies measured quantitatively using an enzyme linked immunosorbent assay (ELISA) compared with immunofluorescent detection of coeliac autoantibodies. PATIENTS: We tested serum samples from 325 IgA deficient subjects, including 78 patients with coeliac disease, 73 disease controls, and 174 blood donors. METHODS: IgG antibodies against human recombinant tTG were measured with an ELISA. IgG antiendomysium antibodies (EMA) were assayed by indirect immunofluorescence on human jejunum and appendix sections. RESULTS: The IgG anti-tTG ELISA had a sensitivity of 98.7% and a specificity of 98.6%, and the correlation with IgG EMA titres was high (r(s)=0.91). One coeliac patient, initially negative in all autoantibody tests, displayed both IgG anti-tTG antibodies and IgG EMA during later gluten exposure. IgG anti-tTG antibodies and EMA titres showed significant decreases (p<0.001) in treated patients. The frequency of IgG anti-tTG autoantibody positivity was 9.8% among IgA deficient blood donors and 11 of the 12 positive subjects with known HLA-DQ haplotypes carried DQ2 or DQ8 alleles. CONCLUSIONS: IgG anti-tTG and IgG EMA autoantibody tests are highly efficient in detecting coeliac disease in IgA deficient patients. The high prevalence of coeliac antibodies among symptom free IgA deficient blood donors who also carry coeliac-type HLA-DQ genes indicates that all IgA deficient persons should be evaluated for coeliac disease.     

Selective IgA Deficiency and Coeliac Disease

Twenty-five children and adults with concomitant coeliac disease and selective IgA deficiency are described. IgG-class reticulin antibodies were positive in 94%. The clinical course of coeliac disease did not differ from that of patients with normal serum IgA level. Patients with IgA deficiency also had other concomitant diseases, especially autoimmune diseases. Patients with selective IgA deficiency have at least a tenfold risk of coeliac disease compared with the population in general.     

Mutagenesis of the catalytic triad of tissue transglutaminase abrogates coeliac disease serum IgA autoantibody binding

BACKGROUND AND AIMS: Tissue transglutaminase (tTG) is an autoantigen in coeliac disease and the related disorder, dermatitis herpetiformis. The detection of autoantibodies directed against tTG is a highly specific marker of coeliac disease; however, it is unclear if there is a role for these autoantibodies in the disease process. The aim of this study was to investigate whether the catalytic triad of tTG is targeted by coeliac disease autoantibodies. METHODS: A full-length wild-type recombinant tTG and a novel site-directed mutagenic variant lacking the catalytic triad were produced in Escherichia coli. Serum samples from 61 biopsy-proven coeliac disease and 10 dermatitis herpetiformis patients were tested for their recognition of both antigens in enzyme-linked immunosorbent assay. RESULTS: Although IgA autoantibodies from sera of patients with coeliac disease and dermatitis herpetiformis bound wild-type tTG well, a dramatic decrease in binding to the mutant tTG was observed with a mean reduction of 79% in coeliac disease and 58% in dermatitis herpetiformis samples. IgG anti-tTG antibodies did not show a similar pattern of reduction, with no overall difference in recognition of the wild-type or mutant tTGs. CONCLUSIONS: These results suggest that the IgA anti-tTG response in coeliac disease and dermatitis herpetiformis is focused on the region of tTG responsible for its transamidation and deamidation reactions, whereas the IgG response may target other regions of the enzyme.     

Coeliac Disease: Frequent Occurrence After Clinical Onset of Insulin-dependent Diabetes Mellitus

Coeliac disease was searched for in a series of 776 children with newly diagnosed IDDM. During the follow-up of 2 to 3 years from diagnosis, reticulin and gliadin antibodies were measured, and a jejunal biopsy was performed in those cases with high levels of antibodies; 19 children were identified with coeliac disease, giving the prevalence of 2.4 %. In only one case had coeliac disease been diagnosed before IDDM. Nine patients with proven coeliac disease were negative for antibodies when IDDM was diagnosed, but became positive within 24 months. All patients found to have coeliac disease were positive for IgA reticulin antibodies, but only 12 of 18 (67 %) showed a high level of IgA gliadin antibodies. Of the 18 patients genotyped for HLA DR locus, 14 (78 %) were positive for DR3 and 10 (56 %) were positive for DR4. DQB1*0201 allele was present in 17 of 18 patients (94 %). Coeliac disease in children with IDDM tends to develop soon after diabetes is diagnosed. Routine screening for coeliac disease is recommended repeatedly during the first years after the diagnosis of IDDM.     

Malignancy and survival in dermatitis herpetiformis: a comparison with coeliac disease.

BACKGROUND--Dermatitis herpetiformis is a lifelong, gluten sensitive skin disease. Patients with dermatitis herpetiformis, similar to patients with coeliac disease not adhering to a gluten free diet, seem to have increased risk for lymphoma. AIMS--This study looked at the occurrence of malignancy and survival of patients with dermatitis herpetiformis and compared the results with those seen in patients with coeliac disease or in the general population. PATIENTS--A total of 305 adult patients with dermatitis herpetiformis diagnosed at the University Hospital of Tampere in 1970-1992 were studied. Most patients started a gluten free diet and at the end of the study 93% of the patients were adhering to the diet. A control group comprised 383 adult patients with coeliac disease, 81% of them adhered to a gluten free diet, 6% had a normal diet, and in 13% the diet history remained unknown. METHODS--The occurrence of malignant diseases and survival of the patients were assessed up to the end of 1993. Standardised incidence ratios (SIR) with 95% confidence intervals were used for the malignant diseases. The survival of the patients was compared with that of the general population. RESULTS--Thirteen (4.3%) patients with dermatitis herpetiformis developed 14 malignant disorders during the follow up (SIR 1.25; 95% confidence intervals 0.68 to 2.09). A non-Hodgkin's lymphoma occurred in four patients with dermatitis herpetiformis, significantly more than expected (SIR 10.3; 2.8-26.3). Thirteen (4.3%) patients with dermatitis herpetiformis died during the follow up but there was no increased general mortality. In coeliac disease, 13 (3.4%) patients developed malignancy (SIR 1.16; 0.62 to 1.97), 31 (8.1%) patients died but the survival rate did not differ from that in the general population. CONCLUSIONS--The incidence of non-Hodgkin's lymphoma was significantly increased in patients with dermatitis herpetiformis. The results also confirm that the patients with dermatitis herpetiformis treated mainly with a gluten free diet have no increased general mortality.     

Selective IgA deficiency and coeliac disease.

Twenty-five children and adults with concomitant coeliac disease and selective IgA deficiency are described. IgG-class reticulin antibodies were positive in 94%. The clinical course of coeliac disease did not differ from that of patients with normal serum IgA level. Patients with IgA deficiency also had other concomitant diseases, especially autoimmune diseases. Patients with selective IgA deficiency have at least a tenfold risk of coeliac disease compared with the population in general.     

Activation of Genes for Superoxide Dismutase,Interleukin-1ß, Tumor Necrosis Factor-a,and Intercellular Adhesion Molecule-1 during Healing of Ischemia-Reperfusion-Induced Gastric Injury

The diagnostic sensitivity and specificity of IgA endomysium antibodies (EmA) and IgA gliadin antibodies (AGA) for coeliac disease (CD) were studied in Swedish children. Indirect immunofluorescence was used for demonstration of EmA and the diffusion-in-gel enzyme-linked immunosorbent assay method for AGA. Serum samples were collected and analysed from 77 consecutive children undergoing small-intestinal biopsy on recognized clinical indications. The diagnostic sensitivity for CD was 98.1% for EmA and 86.5% for AGA. The specificity of the two tests was 92.7% for EmA and 92.7% for AGA in paediatric patients. In addition, 115 sera from control children showed 2.6% positive for EmA and (1.9% positive for AGA.     

In patients with dermatitis herpetiformis distribution of transglutaminase in cutaneous tissue does not differ from controls

BACKGROUND: Dermatitis herpetiformis may be regarded as the cutaneous counterpart of coeliac disease. These conditions are related to the ingestion of gluten and both are characterised by circulating antibodies against tissue transglutaminase. AIMS: To study the distribution of tissue transglutaminase in the skin of dermatitis herpetiformis patients and controls, and to investigate whether the dermal IgA deposits, diagnostic for dermatitis herpetiformis, are related to tissue transglutaminase expression in the skin. METHODS: A series of 11 patients with dermatitis herpetiformis had a 4 mm punch biopsy taken from the uninvolved perilesional skin. A group of 16 controls, undergoing surgical removal of benign nevi, gave perilesional skin. Biopsies were covered with OCT and frozen at -80 degrees C. After washing, skin biopsy sections were incubated with an IgG anti-tissue transglutaminase mouse monoclonal antibody. After washing, sections were incubated with anti-mouse IgG. RESULTS: The anti-tissue transglutaminase monoclonal antibody specifically recognised the basal epidermal cells. This staining was no different between patients and controls. CONCLUSION: Our results suggest that tissue transglutaminase can be recognised in the basal epidermal layer both of patients with dermatitis herpetiformis and controls. Since this distribution does not correspond to the distribution of dermal IgA deposits, it is concluded that dermatitis herpetiformis dermal IgA deposits are not due to antibodies directed against cutaneous tissue transglutaminase.