Community-Based Study of Celiac Disease Autoimmunity Progression in Adults.

BACKGROUND & AIMS: Celiac disease can develop at any age, but outcomes of adults with positive results from serologic tests for tissue transglutaminase antibodies (tTGA) without endoscopic determination of celiac disease (called celiac autoimmunity) have not been thoroughly evaluated. We investigated the proportion of adults with celiac autoimmunity at a community medical center and their progression to celiac disease. METHODS: We analyzed waste blood samples from a community clinic from 15,551 adults for tTGA and, if titer results were above 2 U/mL, for endomysial antibody. The blood samples had been collected at 2 time points (median interval, 8.8 years) from 2006 through 2017. We collected data from the clinic on diagnoses of celiac disease based on duodenal biopsy analysis. RESULTS: Of the serum samples collected at the first time point, 15,398 had negative results for tTGA, and 153 had positive results for tTGA (>4 U/mL). Based on medical records, 6 individuals received a diagnosis of celiac disease, for a cumulative incidence of celiac disease diagnosis of 0.06% (95% confidence interval, 0.01-0.11). Forty-nine (0.32%) individuals with a negative result from the first serologic test for tTGA had a positive result from the second test. Among the 153 adults who were tTGA positive at the first time point, 31 (20%) had a subsequent diagnosis of celiac disease, 81 (53%) remained positive for tTGA without a clinical diagnosis of celiac disease, and 41 (27%) had negative test results for tTGA at the second time point. Higher initial tTGA titers, female sex, and a history of hypothyroidism and autoimmune disease were associated with increased risks of subsequent diagnosis of celiac disease. Interestingly, adults whose first blood sample had a positive test result but second blood sample had a negative result for tTGA were older, had lower-than-average initial tTGA titer results, and had a higher mean body mass index than adults whose blood samples were positive for tTGA at both time points and adults later diagnosed with celiac disease. CONCLUSIONS: In an analysis of serum samples collected from a community clinic an average of 8.8 years apart, we found that fewer than 1% of adults with negative results from an initial test for tTGA have a positive result on a second test. Of adults with positive results from the test for tTGA, only 20% are later diagnosed with celiac disease; the remaining individuals maintain persistent increases in tTGA without diagnoses of celiac disease or have negative results from second tests.

Prevalence and Morbidity of Undiagnosed Celiac Disease From a Community-Based Study.

BACKGROUND & AIMS: Little is known about the prevalence and burden of undiagnosed celiac disease in individuals younger than age 50. We determined the prevalence and morbidity of undiagnosed celiac disease in individuals younger than age 50 in a community. METHODS: We tested sera from 31,255 residents of Olmsted County, Minnesota (<50 y), without a prior diagnosis of celiac disease assay using an assay for IgA against tissue transglutaminase; in subjects with positive test results, celiac disease was confirmed using an assay for endomysial IgA. We performed a nested case-control study to compare the proportion of comorbidities between undiagnosed cases of celiac disease and age- and sex-matched seronegative controls (1:2). Medical records were abstracted to identify potential comorbidities. RESULTS: We identified 338 of 30,425 adults with positive results from both serologic tests. Based on this finding, we estimated the prevalence of celiac disease to be 1.1% (95% confidence interval, 1.0%-1.2%); 8 of 830 children tested positive for IgA against tissue transglutaminase (1.0%; 95% confidence interval, 0.4%-1.9%). No typical symptoms or classic consequences of diagnosed celiac disease (diarrhea, anemia, or fracture) were associated with undiagnosed celiac disease. Undiagnosed celiac disease was associated with increased rates of hypothyroidism (odds ratio, 2.2; P < .01) and a lower than average cholesterol level (P = .03) and ferritin level (P = .01). During a median follow-up period of 6.3 years, the cumulative incidence of a subsequent diagnosis with celiac disease at 5 years after testing was 10.8% in persons with undiagnosed celiac disease vs 0.1% in seronegative persons (P < .01). Celiac disease status was not associated with overall survival. CONCLUSIONS: Based on serologic tests of a community population for celiac disease, we estimated the prevalence of undiagnosed celiac disease to be 1.1%. Undiagnosed celiac disease appeared to be clinically silent and remained undetected, but long-term outcomes have not been determined.

The potential utility of tight junction regulation in celiac disease: focus on larazotide acetate.

Celiac disease (CD) is a common chronic immune disease triggered by gluten. Gliadin peptides pass through the epithelial layers, either paracellularly or transcellularly, to launch a potent adaptive immune response in the lamina propria. This aberrant immune response leads to diverse gastrointestinal and extra-gastrointestinal symptoms. Currently, the only treatment for CD is a strict lifelong adherence to a gluten-free diet (GFD), which can be challenging. An early effect of gluten in CD is an increase in gut permeability. Larazotide acetate, also known as AT-1001, is a synthetic peptide developed as a permeability regulator primarily targeting CD. In vitro studies indicate that larazotide acetate is capable of inhibiting the actin rearrangement caused by gliadin and clinical studies have been conducted using this peptide as a therapy for CD.

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.

Superantigens produced by catheter-associated Staphylococcus aureus elicit systemic inflammatory disease in the absence of bacteremia.

SAgs, produced by Staphylococcus aureus, play a major role in the pathogenesis of invasive staphylococcal diseases by inducing potent activation of the immune system. However, the role of SAgs, produced by S. aureus, associated with indwelling devices or tissues, are not known. Given the prevalence of device-associated infection with toxigenic S. aureus in clinical settings and the potency of SAgs, we hypothesized that continuous exposure to SAgs produced by catheter-associated S. aureus could have systemic consequences. To investigate these effects, we established a murine in vivo catheter colonization model. One centimeter long intravenous catheters were colonized with a clinical S. aureus isolate producing SAgs or isogenic S. aureus strains, capable or incapable of producing SAg. Catheters were subcutaneously implanted in age-matched HLA-DR3, B6, and AE(o) mice lacking MHC class II molecules and euthanized 7 d later. There was no evidence of systemic infection. However, in HLA-DR3 transgenic mice, which respond robustly to SSAgs, the SSAg-producing, but not the nonproducing strains, caused a transient increase in serum cytokine levels and a protracted expansion of splenic CD4(+) T cells expressing SSAg-reactive TCR Vß8. Lungs, livers, and kidneys from these mice showed infiltration with CD4(+) and CD11b(+) cells. These findings were absent in B6 and AE(o) mice, which are known to respond poorly to SSAgs. Overall, our novel findings suggest that systemic immune activation elicited by SAgs, produced by S. aureus colonizing foreign bodies, could have clinical consequences in humans.

Isotretinoin exposure and risk of inflammatory bowel disease.

IMPORTANCE Isotretinoin is the standard treatment for refractory severe nodulocystic acne.A true association between prior isotretinoin use and development of inflammatory bowel disease (IBD) is uncertain. Addressing the reality of this association is important in decision making for both the clinician and the patient when isotretinoin treatment is indicated.OBJECTIVE To assess the risk of IBD mainly in patients with acne with and without isotretinoin exposure.DESIGN, SETTING, AND PARTICIPANTS In this retrospective, single-center study, the electronic medical records of patients who were primarily seeking acne treatment were reviewed for isotretinoin exposure. International Classification of Diseases, Ninth Revision (ICD-9) codes were used to search for IBD diagnosis. participants included 1078 patients from 1995 to 2011,with isotretinoin referenced in their medical records, and who had ongoing local medical care defined as having had a serum sample collected between 2006 to 2011 for any reason while an Olmsted County, Minnesota, resident at the time of serum sample collection.EXPOSURES The exposed group included the patients with confirmed prior isotretinoin exposure (n = 576), and the nonexposed group were defined as patients who never received isotretinoin or received it after the diagnosis of IBD (n = 502).MAIN OUTCOMES AND MEASURES Risk of IBD among isotretinoin-exposed vs non exposed patients.RESULTS Both groups were comparable by race, prior systemic antibiotic use, and systemic tetracycline use. Inflammatory bowel disease developed less frequently in the isotretinoin-exposed group vs the nonexposed group (0.9%vs 2.6%; P = .03; unadjusted odds ratio [OR], 0.33; 95%CI, 0.12-0.93; P = .04). The negative association between isotretinoin exposure and IBD remained after adjusting for sex (OR, 0.28; 95%CI, 0.10-0.80;P = .02) and for sex and non acne indication (OR, 0.28; 95%CI, 0.10-0.79; P = .02).CONCLUSIONS AND RELEVANCE Our study did not show an increased risk of IBD with prior isotretinoin use. If anything, the risk seemed to be decreased. Although these results may be due to chance given the small number of IBD cases, the anti-inflammatory and immune-modulating effects of isotretinoin may be worth exploring.

Superantigen profiling of Staphylococcus aureus infective endocarditis isolates.

The frequency of superantigen production among Staphylococcus aureus isolates associated with endocarditis is not well defined. We tested 154 S. aureus isolates from definite infective endocarditis cases for the presence of staphylococcal enterotoxins A-E, H, and TSST-1 by PCR, enzyme-linked immunosorbent assay, and using an HLA-DR3 transgenic mouse splenocyte proliferation assay. Sixty-three isolates (50.8%) tested positive for at least 1 superantigen gene, with 21 (16.9%) testing positive for more than 2. tst (28.6%) was most common, followed by seb (27%), sea (22.2%), sed (20.6%), see (17.5%), and sec (11.1%). Of 41 methicillin-resistant S. aureus, 21 had superantigen genes, with sed being more frequently detected in this group compared to methicillin-susceptible S. aureus (P < 0.05). Superantigen genes were not associated with mortality (P = 0.81). 75% of PCR-positive isolates induced robust splenocyte proliferation. Overall, more than half of S. aureus isolates causing endocarditis carry superantigen genes, of which most are functional.

Evaluation of Tigecycline Activity Against Methicillin-Resistante Staphylococcus aureus Isolated from Biological Samples.

Tigecycline is a new glycylcycline antibiotic structurally similar to minocycline antibiotic. It has broad spectrum activity, including Staphylococcus aureus infections. This is the first study that evaluated the activity of Tigecycline against Staphylococcus aureus isolated from biological samples in Iran. In vitro activity of tigecycline against 160 Staphylococcus aureus including 99 methicillin-resistant S. aureus and 61 methicillin-susceptible S. aureus from inpatients at Imam Khomeini Hospital, Tehran, Iran was assessed. Bacterial susceptibility tests were performed by the disk diffusion method and also E-test for methicillin-resistant S. aureus isolates. All isolated had inhibition zone of ≥ 19 mm, with the minimum inhibitory concentration 50 (MIC50) and MIC90 of 0.19 and 0.5 µg/mL, respectively. The study results indicated that all methicillin-resistant S. aureus and methicillin-susceptible S. aureus isolates were susceptible to tigecycline.