The idiopathic hypereosinophilic syndrome

Using a systems biology approach, we discovered and dissected a three-way interaction between the immune system, the intestinal epithelium and the microbiota. We found that, in the absence of B cells, or of IgA, and in the presence of the microbiota, the intestinal epithelium launches its own protective mechanisms, upregulating interferon-inducible immune response pathways and simultaneously repressing Gata4-related metabolic functions. This shift in intestinal function leads to lipid malabsorption and decreased deposition of body fat. Network analysis revealed the presence of two interconnected epithelial-cell gene networks, one governing lipid metabolism and another regulating immunity, that were inversely expressed. Gene expression patterns in gut biopsies from individuals with common variable immunodeficiency or with HIV infection and intestinal malabsorption were very similar to those of the B cell–deficient mice, providing a possible explanation for a longstanding enigmatic association between immunodeficiency and defective lipid absorption in humans.

/pdf/crosstalk-between-b-lymphocytes-microbiota-and-the-ql6d7ktw42.pdf

Crosstalk between B lymphocytes, microbiota and the intestinal epithelium governs immunity versus metabolism in the gut

Interleukin 15 mediates epithelial changes in celiac disease

The FIP1L1-PDGFRα fusion tyrosine kinase in hypereosinophilic syndrome and chronic eosinophilic leukemia: implications for diagnosis, classification, and management

The intestinal epithelium has one of the highest rates of cellular turnover in a process that is tightly regulated. As the transit-amplifying progenitors of the intestinal epithelium generate ~300 cells per crypt every day, regulated cell death and sloughing at the apical surface keeps the overall cell number in check. An aberrant increase in the rate of intestinal epithelial cell (IEC) death underlies instances of extensive epithelial erosion, which is characteristic of several intestinal diseases such as inflammatory bowel disease and infectious colitis. Emerging evidence points to a crucial role of necroptosis, autophagy and pyroptosis as important modes of programmed cell death in the intestine in addition to apoptosis. The mode of cell death affects tissue restitution responses and ultimately the long-term risks of intestinal fibrosis and colorectal cancer. A vicious cycle of intestinal barrier breach, misregulated cell death and subsequent inflammation is at the heart of chronic inflammatory and infectious gastrointestinal diseases. This Review discusses the underlying molecular and cellular underpinnings that control programmed cell death in IECs, which emerge during intestinal diseases. Translational aspects of cell death modulation for the development of novel therapeutic alternatives for inflammatory bowel diseases and colorectal cancer are also discussed.

Cell death in the gut epithelium and implications for chronic inflammation

Immunofluorescence studies of plasma cells were performed on small intestinal and colonic biopsies obtained from a series of patients with acquired immunodeficiency syndrome or the “AIDS related complex” plus homosexual male and heterosexual controls. The AIDS group was significantly depleted of IgA plasma cells compared to the control groups. In contrast, the numbers of IgM plasma cells were increased in the AIDS and homosexual control groups compared to the heterosexuals. Plasma cell fluorescence intensities for IgA and IgM were decreased in the AIDS patients, implying less cytoplasmic immunoglobulin per cell. The frequency of IgA plasma cell depletion did not differ in men and women, patients with opportunistic infections or Kaposi's sarcoma, or in patients with and without gastrointestinal symptoms. The extent of IgA plasma cell depletion did not correlate with serum IgA concentrations. IgA plasma cell numbers also did not correlate with selected parameters of nutritional status and intestinal absorption. Studies of salivary IgA output demonstrated decreased secretion of soluble IgA in AIDS patients, and an increased secretion of IgA in particulate form. These results suggest that abnormalities in IgA secretion occur in AIDS and might influence its clinical manifestations.

Intestinal plasma cell alterations in acquired immunodeficiency syndrome

Colonic carcinogenesis is accompanied by progressive genetic changes and alterations in growth control. To examine whether abnormalities of apoptosis are involved in carcinogenesis, we examined epithelial apoptosis in formalin-fixed normal and neoplastic colon by terminal uridine deoxynucleotide nick end-labeling (TUNEL) histochemistry. In normal colon, resection margins, and hyperplastic polyps, TUNEL-positive cells comprised around 3% of total colonocytes, with over 85% of these cells located in surface epithelium between crypts. In adenomas, there were significantly fewer TUNEL-positive cells at the luminal surface than normal (1.82±0.51% of epithelial cells, compared with 12.1±2.3%,P<0.05) and a trend to increased numbers at the crypt base (2.70±0.98% compared with 0.65±0.15%). Carcinomas contained fewer TUNEL-positive cells than normal (1.7±0.27%), and they are randomly distributed. Transitional mucosa had significantly more TUNEL-positive colonocytes than normal (11.0±3.0%,P<0.005), both at the surface and crypt base. These results show that colonocyte apoptosis normally occurs mainly in luminal cells but that early during carcinogenesis the distribution and quantity of apoptotic cells changes.

Abnormalities of epithelial apoptosis in multistep colorectal neoplasia demonstrated by terminal deoxyuridine nick end labeling

To the Editor.— The mucous membranes appear to be particularly vulnerable to opportunistic infections in patients with the acquired immunodeficiency syndrome (AIDS). Such infections may arise either from the external environment or by extension from a systemic focus. We wish to report a patient with AIDS and a chronic rhinitis and sinusitis due to cytomegalovirus (CMV) that led to an erroneous impression of CMV pneumonitis. Report of a Case.— A 33-year-old homosexual man was evaluated for interstitial pneumonitis. There was a history of fever, weight loss, intermittent diarrhea, anorectal herpes infection, and previous admissions for an unspecified pneumonia and staphylococcal sepsis—the latter felt to be caused by nasal vestibulitis. On the second hospital day, pneumocystis pneumonia was disgnosed by bronchoalveolar lavage. No biopsies were performed. The patient was treated with trimethoprim sulfate and had clinical resolution of symptoms, although temperatures to 38.8 °C continued. The patient was anemic and lymphopenic.

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=jama&articleId=398776&pdfFileName=jama_253_21_018.pdf

Disseminated CMV infection.

A rare case of asymptomatic cancer of the ascending colon presenting as a subcutaneous groin mass is reported. At the time of right hemicolectomy with resection of the groin mass there was no sign of incontinuity spread or lymph blockage. Sequential determination of carcinoembryonic antigen levels (CEA) in serum reflected the reduction in tumor mass after surgery as well as subsequent recurrences of disease in the groin and in the lung after 2 years. Immunoperoxidase staining of the primary tumor and the metastases showed strong positivity for CEA confirming the origin of the serum CEA. There have been no signs of liver involvement. The route of spread of this unusual metastasis is not known.

An unusual presentation of colon cancer.

The endoscopic localization of a gastrinoma in the afferent loop of a gastrojejunostomy.

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