Characterization of autoimmune eye disease in association with Down's syndrome.

BACKGROUND: Autoimmunity and deficiency of the transcription factor autoimmune regulator protein (AIRE) are known associations with Down syndrome (DS). Lack of AIRE abrogates thymic tolerance. The autoimmune eye disease associated with DS has not been characterized. We identified a series of subjects with DS (n = 8) and uveitis. In three consecutive subjects, we tested the hypothesis that autoimmunity to retinal antigens might be a contributing factor. SUBJECTS/METHODS: This was a multicentred, retrospective case series. Deidentified clinical data of subjects with both DS and uveitis were collected via questionnaire by uveitis-trained ophthalmologists. Anti-retinal autoantibodies (AAbs) were detected using an Autoimmune Retinopathy Panel tested in the OHSU Ocular Immunology Laboratory. RESULTS: We characterized eight subjects (mean age 29 [range, 19-37] years). The mean age of detected uveitis onset was 23.5 [range, 11-33] years. All eight subjects had bilateral uveitis (p < 0.001 based on comparison to published university referral patterns), with anterior and intermediate uveitis found in six and five subjects respectively. Each of three subjects tested for anti-retinal AAbs was positive. Detected AAbs included anti-carbonic anhydrase II, anti-enolase, anti-arrestin, and anti-aldolase. DISCUSSION: A partial deficiency in the AIRE on chromosome 21 has been described in DS. The similarities in the uveitis presentations within this patient group, the known autoimmune disease predisposition in DS, the recognized association of DS and AIRE deficiency, the reported detection of anti-retinal antibodies in patients with DS in general, and the presence of anti-retinal AAbs in three subjects in our series supports a causal association between DS and autoimmune eye disease.

Prevalence and predictors of colon polyps in patients with skin tags: A cross sectional study.

BACKGROUND: Acrochordons (fibroepithelial polyps, skin tags, papillomas) are common benign neoplasms of the skin. AIM: To identify the prevalence of colonic polyps among patients presenting with skin tags and to determine a useful criteria for screening with colonoscopy. METHODS: Two hundred patients who fulfilled the selection criteria underwent physical, biochemical evaluation (fasting blood sugar (FBS), body mass index (BMI) calculation, occult blood in stool), and histopathological examination of the skin tags. Colonoscopy was performed in patients with positive blood in stool, and any polyps identified were resected or biopsied. RESULTS: Occult blood in stool was insignificantly detected in 12 (6%) of the 200 subjects (p < 0.001), and they were referred for colonoscopy. A prevalence rate of 3.5% was reported, and of twelve colonoscopies performed, three patients were polyp-free, two were diagnosed with ulcerative colitis (UC), and seven patients were diagnosed with polyps that were removed and/or biopsied (p = 0.421). Of the seven polyps, three were hemorrhoidal polyps and the four other polyps were adenomatous polyps (villous adenoma). CONCLUSION: The mere presence of skin tags does not significantly correlate with existence of colonic polyps and does not justify screening colonoscopy unless other metabolic, GIT, and biochemical markers are identified.

Therapeutic implications of assessment of serum zinc levels in patients with vitiligo: A patient controlled prospective study.

Vitiligo is an autoimmune disease characterized by patches of depigmentation. Zinc is an antiapoptotic molecule that exhibits antioxidant properties. The study aimed to investigate the serum levels of zinc in vitiligo patients compared to healthy controls and to whether exists a correlation between disease severity and serum levels of zinc. Fifty patients with vitilgo (group A) and 50 age and sex matched healthy controls (group B) were recruited and serum zinc level was measured using atomic absorption spectrophotometry and results were compared and correlated to each other and to disease severity and extension. The mean serum zinc levels in group A was 50.93 ± 11.02 in comparison to a mean of 77.09 ± 12.16 in group B (P = .049, T = -1.993). Vitiligo area severity index (VASI) scores in the vitiligo group ranged from 0.5 to 27 with a mean ± SD of (9.19 ± 4.47). A high statistically significant negative correlation was demonstrated between serum zinc levels and the extension of vitiligo (P value = .0001 and R value = - 0.835). A significant association exists between vitiligo and serum zinc levels. Serum zinc levels correlated negatively with vitiligo disease severity and extension. Zinc supplementation and use can be of potential importance in setting vitiligo treatment protocols.

Contribution of pre-existing vascular disease to allograft vasculopathy in a murine model.

Allograft vasculopathy (AV) has emerged as a major obstacle for long-term graft survival after cardiac transplantation. The shortage of donor hearts has meant fewer restrictions have been placed on acceptable hearts over the past few years resulting in an increase in the number of older hearts in the donor pool. This increase has subsequently led to the increase of donor hearts containing pre-existing disease. The importance of this pre-existing donor vascular disease in AV outcomes remains controversial. In this study we address this by taking advantage of the fact that B6 Apolipoprotein-E knockout mice develop atherosclerotic lesions in their aortic tracts that closely model human naturally occurring vascular disease. By using these mice as donors, we transplant known levels of pre-existing disease into fully disparate (C3H) recipients. Cyclosporin A is used to prevent acute rejection and allow for allograft vasculopathy. We found that pre-existing lesions are retained in this model after transplantation and that they contribute to increase in lesion size and to increased lumenal narrowing. The de novo AV lesions overlay the pre-existing lesions and this leads to areas of eccentric lesion formation in the vessels with likely accompanying exacerbation of flow perturbation.

Immunologic targets in the etiology of allograft vasculopathy: endothelium versus media.

The respective roles of the endothelium and the media as allo-immune targets in the generation of allograft vasculopathy (AV) have yet to be clearly defined. Although endothelial damage has been implicated in the progression of AV, evidence from mechanical vascular injury models suggests that medial injury may play a more dominant role. The overall objective of this research was to determine the relative importance of the endothelium versus the media as a target for immune injury and induction of AV. To investigate this we developed a novel model which involved the creation of chimeric aortic segments. To accomplish this we removed aortic segments from C3H/HeJ (C3H) mice and stripped them of endothelium by a short pulse with EDTA. The stripped C3H grafts were implanted into immunodeficient C57BL/6 (B6) RAG1(-/-) mice for a period of 21 days. As the immunodeficient mice did not mount an allo-immune response to the grafts, the endothelium was renewed by normal repair mechanisms. The new endothelium was recipient in origin, resulting in a chimeric graft with C3H media and B6 endothelium. We confirmed complete denudement by immunocytochemistry for endothelial specific markers, as well as by transmission and scanning electron microscopy. Replacement of endothelium with recipient endothelial cells was confirmed by immunocytochemistry, electron microscopy and by using a green fluorescent protein mouse transplant combination. Subsequent re-transplantation of the chimeric grafts into either B6 or C3H recipients demonstrated that an allogeneic media is more important than an allogeneic endothelium in inducing robust AV.

Effects of altered temperature and precipitation on desert protozoa associated with biological soil crusts.

Biological soil crusts are diverse assemblages of bacteria, cyanobacteria, algae, fungi, lichens, and mosses that cover much of arid land soils. The objective of this study was to quantify protozoa associated with biological soil crusts and test the response of protozoa to increased temperature and precipitation as is predicted by some global climate models. Protozoa were more abundant when associated with cyanobacteria/lichen crusts than with cyanobacteria crusts alone. Amoebae, flagellates, and ciliates originating from the Colorado Plateau desert (cool desert, primarily winter precipitation) declined 50-, 10-, and 100-fold, respectively, when moved in field mesocosms to the Chihuahuan Desert (hot desert, primarily summer rain). However, this was not observed in protozoa collected from the Chihuahuan Desert and moved to the Sonoran desert (hot desert, also summer rain, but warmer than Chihuahuan Desert). Protozoa in culture began to encyst at 37 degrees C. Cysts survived the upper end of daily temperatures (37-55 degrees C), and could be stimulated to excyst if temperatures were reduced to 15 degrees C or lower. Results from this study suggest that cool desert protozoa are influenced negatively by increased summer precipitation during excessive summer temperatures, and that desert protozoa may be adapted to a specific desert's temperature and precipitation regime.