Shadi Rashtak

Comparative Usefulness of Deamidated Gliadin Antibodies in the Diagnosis of Celiac Disease

BACKGROUND & AIMS Serologic tests are used frequently in celiac disease diagnosis. Gliadin antibodies generally lack the accuracy required for proper diagnosis. We evaluated the value of deamidated gliadin antibody measurements in the diagnosis and follow-up evaluation of celiac disease and compared their potential usefulness with that of gliadin and tissue-transglutaminase antibodies. METHODS We tested deamidated gliadin, gliadin, and tissue-transglutaminase-immunoglobulin (Ig)A and -IgG in 216 biopsy-selected subjects including 92 biopsy-proven untreated celiac patients (46% with total villous atrophy and 54% with partial villous atrophy) and 124 biopsy-proven nonceliac controls. Fifty-nine celiac patients also were tested after treatment with a gluten-free diet. Antibodies were measured by commercial enzyme-linked immunosorbent assays. Deamidated gliadin-IgA+G was detected using a conjugate reactive to both isotypes, which gives a positive if either isotype is present. RESULTS The sensitivity, specificity, and accuracy of deamidated gliadin-IgA (74%, 95%, and 86%), deamidated gliadin-IgG (65%, 98%, and 84%), and deamidated gliadin-IgA+G (75%, 94%, and 86%) were superior to gliadin-IgA (63%, 90%, and 79%) (P < .05) and gliadin-IgG (42%, 90%, and 69%) (P < .01), and were similar to tissue-transglutaminase-IgA (78%, 98%, and 90%) before treatment. The sensitivity of IgA isotype for all tests was significantly greater in celiac patients with total villous atrophy compared with those with partial villous atrophy (P < .05). The proportion of positive test results for all tests decreased significantly after treatment (P < .0001). CONCLUSIONS Deamidated gliadin antibody is a better diagnostic test for celiac disease than the conventional gliadin antibody testing; although histopathology remains the gold standard test for diagnosis of celiac patients.

From furuncle to axillary web syndrome: shedding light on histopathology and pathogenesis.

Axillary web syndrome (AWS) is defined as a cord-like structure extending from the axilla to the medial arm following axillary surgery in women with breast cancer. There is only limited literature on the pathogenesis of this syndrome and the etiology of the cord. A 57-year-old man presented with a band-like skin depression and tightness over the medial aspect of his arm extending from the axilla to the antecubital fossa following development of a furuncle in the ipsilateral axilla. Histopathologic examination of the ‘band’ revealed fibroblastic proliferation surrounding the lymphatic vessel which was identified by presence of an obvious valve as well as positive staining for D2-40, a specific marker for lymphatic endothelium. This is the first report of AWS following axillary furunculosis. This case adds to the limited data on the histopathology of AWS, further confirming the etiology of the ‘cord’ to be of lymphatic origin.

Serology of celiac disease in gluten-sensitive ataxia or neuropathy: Role of deamidated gliadin antibody

The role and relevance of deamidated gliadin antibodies specific for celiac disease in gluten-sensitive ataxia/neuropathy is unknown. We investigated the association of celiac-specific serology with gluten-sensitive ataxia/neuropathy, in patients with and without gliadin-induced enteropathy. 51 patients with unexplained ataxia/neuropathy suspected to have gluten sensitivity were included in the study and their serum celiac-specific markers were measured. Deamidated gliadin-IgA (83% vs. 22%), deamidated gliadin-IgG (50% vs. 3%), tissue transglutaminase-IgA (78% vs. 11%), and anti-endomysial-IgA (70% vs. 0%), were significantly more positive in ataxia/neuropathy patients with celiac disease versus those without enteropathy (P<0.001). Our findings suggest that the serological profile of gluten-sensitive ataxia/neuropathy without intestinal involvement lacks the recognition of deamidated gliadin and tissue transglutaminase epitopes.

Celiac sprue: a unique autoimmune disorder

Celiac sprue (CS) is a gluten-sensitive enteropathy with many autoimmune features. CS involves multiple organs through immune and nonimmune processes, and is frequently associated with other autoimmune disorders. This article reviews the co-occurrence of CS with autoimmune disorders of the cutaneous, nervous, endocrine, musculoskeletal, gastrointestinal and cardiovascular systems. The types of autoimmune disorders associated with CS and the prevalence of CS in other autoimmune disorders are also discussed. A brief review of the literature on the potential mechanisms behind these associations and the therapeutic effects of a gluten-free diet for autoimmune comorbidities in CS is also provided.

Spontaneous lupus-like syndrome in HLA-DQ2 transgenic mice with a mixed genetic background

To investigate the role of HLA-DQ2 in the pathogenesis of associated immune disorders, we generated transgenic mice that expressed HLA-DQ2 in the absence of endogenous murine class II molecules (AE0DQ2). These AE0DQ2 mice with a mixed genetic background spontaneously developed skin lesions on their ears, whereas control AE0DQ6 genotype control mice (also with a mixed genetic background) did not. The skin lesions were characterized by deep subepidermal blistering with hydropic degeneration and lymphoid infiltration in the subepidermal area as determined by histopathology. Immunofluorescence analysis revealed thick band-like granular deposition of IgG, IgM, and a thin band of IgA deposition along the basement membrane. AE0DQ2 mice also developed significant and progressive hematuria and proteinuria as compared with the AE0DQ6 mice (p < 0.05). Histopathology showed immune complex deposits in the glomeruli of AE0DQ2 mice. Immunofluorescence analysis showed progressive mesangial and capillary wall deposition of IgA, IgM, IgG and C1q in the kidney. With electron microscopy, the deposits showed a ‘fingerprint’ substructure; and tubuloreticular structures were identified within endothelial cells. Conversely, these changes were not observed in AE0DQ6 mice. Serum anti-double stranded (ds)DNA IgM and IgG levels were also significantly elevated among AE0DQ2 mice compared with AE0DQ6 mice (p < 0.001). In conclusion, AE0DQ2 mice spontaneously develop an autoimmune lupus-like syndrome and are useful model for this disease. It remains to be determined whether genetic admixture played a role in the development of this systemic lupus erythematosus-like syndrome in HLA-DQ2 transgenic mice. Lupus (2010) 19, 815—829.

Does urticaria risk increase in patients with celiac disease? A large population-based cohort study

BACKGROUND Case reports and smaller case-control studies suggest an association between celiac disease (CD) and urticaria but risk estimates have varied considerably across studies and as yet there are no studies on CD and the risk of future urticaria. OBJECTIVE To examine the association between CD and urticaria. METHODS We identified 28,900 patients with biopsy-verified CD (equal to Marsh stage 3) and compared them with 143,397 age- and sex-matched controls with regards to the risk of urticaria and chronic urticaria (duration ≥6 weeks). Hazard ratios (HRs) were estimated using a Cox regression model. RESULTS During follow-up, 453 patients with CD and no previous diagnosis of urticaria developed urticaria (expected n = 300) and 79 of these 453 had chronic urticaria (expected n = 41). The corresponding HRs were 1.51 for any urticaria (95%CI = 1.36-1.68) and 1.92 for chronic urticaria (95%CI = 1.48-2.48). The absolute risk for urticaria in CD was 140/100,000 person-years (excess risk = 47/100,000 person-years). Corresponding figures for chronic urticaria were 24/100,000 person-years and 12/100,000 person-years. Patients with CD were also at increased risk of having both urticaria (odds ratio, OR = 1.31; 95%CI = 1.12-1.52) and chronic urticaria (OR = 1.54; 95%CI = 1.08-2.18) prior to the CD diagnosis. CONCLUSION This study suggests that CD is associated with urticaria, especially chronic urticaria.

Experiences with animal models of dermatitis herpetiformis: A review

Dermatitis herpetiformis (DH) is caused by the consumption of gluten, which is also the trigger for celiac disease. DH is currently considered to be the skin manifestation of celiac disease, as both diseases have some degree of gluten-sensitive enteropathy. The human leukocyte antigens class II genes, DQ2 and DQ8, are tightly associated with both diseases, and there is an increased level of anti-gliadin antibodies in both diseases. Animal models of gluten sensitivity have been used to better understand the pathogenesis of both diseases. This paper describes these different models and discusses how certain elements of these models contribute to the development of DH.

Celiac disease: Diagnosis of celiac disease in pediatric patients

Children and adolescents with untreated celiac disease display disease-related, histological alterations in the duodenal bulb, according to a new study. In 16 of the 665 patients enrolled in the study, lesions were confined to the duodenal bulb.

Diagnosis of celiac disease in pediatric patients.

Children and adolescents with untreated celiac disease display disease-related, histological alterations in the duodenal bulb, according to a new study. In 16 of the 665 patients enrolled in the study, lesions were confined to the duodenal bulb.

Isotretinoin Exposure and Risk of Celiac Disease

Background Isotretinoin (13-cis retinoic acid) is a metabolite of vitamin A and has anti-inflammatory and immunoregulatory effects; however, a recent publication by DePaolo et al. demonstrated that in the presence of IL-15, retinoic acid can act as an adjuvant and promote inflammation against dietary proteins. Objective To evaluate the risk of overt and latent celiac disease (CD) among users of isotretinoin. Material and Methods Medical records of patients from 1995 to 2011 who had a mention of isotretinoin in their records (N = 8393) were searched for CD diagnosis using ICD-09CM codes. Isotretinoin exposure was compared across overt CD patients and their age- and gender-matched controls from the same pool. To evaluate the risk of latent CD with isotretinoin exposure, patients were overlapped with a community-based list of patients with waste serum samples that were tested for CD serology, excluding those with overt CD (2006–2011). Isotretinoin exposure was defined as the use of isotretinoin prior to CD diagnosis or serology. Results Of 8393 patients, 25 had a confirmed CD diagnosis. Compared to matched controls (N = 75), isotretinoin exposure was not significantly different between overt CD patients versus controls (36% versus 39%, respectively; P = 0.712). Likewise, latent CD defined as positive serology was not statistically different between isotretinoin exposed (N = 506) versus non-exposed (N = 571) groups (1.8% versus 1.4%, respectively; P = 0.474). Conclusions There was no association between isotretinoin use and risk of either overt or latent CD.