Preexisting antigen-specific immune responses are modulated by oral KLH feeding in humans.

Oral tolerance is the antigen-specific inhibition of a systemic immune response after oral antigen uptake and well established in animal models. We recently showed that keyhole limpet hemocyanin (KLH) feeding modulates subsequently induced systemic immune responses in humans as well. In the present study, we investigated whether oral KLH can also modulate preexisting antigen-specific systemic B- and T-cell responses.

Dendritic cells from human mesenteric lymph nodes in inflammatory and non-inflammatory bowel diseases: subsets and function of plasmacytoid dendritic cells.

Plasmacytoid dendritic cells (pDC) in mesenteric lymph nodes (MLN) may be important regulators of both inflammatory and non-inflammatory mucosal immune responses but human studies are rare. Here we compare pDC from human MLN and peripheral blood (PB) by phenotype and function. MLN from patients with or without inflammatory bowel disease (IBD) undergoing colon surgery and PB from patients with IBD and from controls were used to isolate mononuclear cells.

Impaired peripheral Th1 CD4+ T cell response to Escherichia coli proteins in patients with Crohn's disease and ankylosing spondylitis.

Background: To clarify the impact of T cell responses towards enteric antigens for chronic intestinal inflammation, we determined T helper 1 reactivity towards conserved Escherichia coli proteins in patients with Crohn's disease (CD) and healthy individuals and patients with ankylosing spondylitis (AS), who also often show microscopic inflammatory lesions within the gut or even develop overt inflammatory bowel disease.

Methods: We determined the frequency of IFNγ+CD40L+ cells/CD4+ T cells after stimulation of whole blood with pools of E. coli proteins.

Modulation of systemic antigen-specific immune responses by oral antigen in humans.

Oral antigen uptake can induce systemic immune responses ranging from tolerance to immunity. However, the underlying mechanisms are poorly understood, especially in humans. Here, keyhole limpet hemocyanin (KLH), a neoantigen which has been used in earlier studies of oral tolerance, was fed in a repeated low-dose and a single high-dose protocol to healthy volunteers.

Significant differences between Crohn's disease and ulcerative colitis regarding the impact of body mass index and initial disease activity on responsiveness to azathioprine: results from a European multicenter study in 1,176 patients.

In a survey comprising 1,176 patients with inflammatory bowel disease (IBD) we recently showed that azathioprine (AZA) beyond 4 years is beneficial in ulcerative colitis (UC) patients and in a subset of Crohn's disease (CD) patients. Here, we show for the first time that azathioprine responsiveness depends on body mass index (BMI). The relationship is reciprocal in UC and CD, with a better outcome in UC patients with a BMI<25 and in CD patients with a BMI>25.

Oral polio vaccination leads to oligoclonal expansion of TCRBV16+ and TCRBV13+ T cells in the colon of rhesus macaques.

In studying immune responses towards the poliovirus, data about T cell mediated immunity in the intestine as the main portal of viral entry in disease and vaccination is lacking. We treated two macaques with oral Polio vaccine and collected duodenal and colonic biopsy specimens. RNA isolation, reverse transcription, and polymerase chain reaction were performed for fragment analysis of the complementarity determining region 3 (CDR3) of the T cell receptor beta chain variable region (TCRBV), followed by subcloning and sequencing of expanded bands.

Autoregulation of Th1-mediated inflammation by twist1.

The basic helix-loop-helix transcriptional repressor twist1, as an antagonist of nuclear factor kappaB (NF-kappaB)-dependent cytokine expression, is involved in the regulation of inflammation-induced immunopathology. We show that twist1 is expressed by activated T helper (Th) 1 effector memory (EM) cells. Induction of twist1 in Th cells depended on NF-kappaB, nuclear factor of activated T cells (NFAT), and interleukin (IL)-12 signaling via signal transducer and activator of transcription (STAT) 4.

Pulmonary fibrosis after chemotherapy with oxaliplatin and 5-fluorouracil for colorectal cancer.

Background: Chemotherapy with oxaliplatin and 5-fluorouracil (5-FU)/folinic acid is the standard first-line therapy of metastatic colorectal carcinoma and has shown activity in several other malignancies. This regimen is mostly well tolerated. Known side effects include myelosuppression, nausea/vomiting and neuropathies; acute pulmonary toxicity has only been described in very few reports.

Homologous high-throughput expression and purification of highly conserved E coli proteins.

Background: Genetic factors and a dysregulated immune response towards commensal bacteria contribute to the pathogenesis of Inflammatory Bowel Disease (IBD). Animal models demonstrated that the normal intestinal flora is crucial for the development of intestinal inflammation. However, due to the complexity of the intestinal flora, it has been difficult to design experiments for detection of proinflammatory bacterial antigen(s) involved in the pathogenesis of the disease.

Psychological treatment may reduce the need for healthcare in patients with Crohn's disease.

Background: Few published studies examine the influence of psychological treatment on health care utilization in Crohn's disease.

Methods: The present substudy of a prospective, randomized, multicenter trial conducted in 69 of 488 consecutive Crohn's disease (CD) patients was designed to investigate the way in which healthcare utilization is influenced by psychotherapy and relaxation in addition to standardized glucocorticoid therapy. Before and after a 1-year period of standardized somatic treatment the psychotherapy and control groups were compared with regard to hospital and sick-leave days.

Long-term effectiveness of azathioprine in IBD beyond 4 years: a European multicenter study in 1176 patients.

In Crohn's disease the optimal duration of azathioprine treatment is still controversial and for ulcerative colitis only limited data are available to support its efficacy. Charts of 1176 patients with IBD from 16 European centers were analyzed. Flare incidences and steroid dosages were assessed for the time before and during treatment and after discontinuation.

Mucosal but not peripheral FOXP3+ regulatory T cells are highly increased in untreated HIV infection and normalize after suppressive HAART.

Recent evidence indicates that regulatory T cells (T(regs)) play an important role in HIV infection. However, although the gastrointestinal mucosa is a key compartment in HIV disease, no data on mucosal T(regs) in HIV infection are available. In this study, we compared the frequency of T(regs) in duodenal mucosa and peripheral blood (PB) of 13 treatment-naive and 13 suppressively treated HIV-infected patients with that of 6 patients with norovirus infection and 12 healthy controls.

The role of probiotics and antibiotics in regulating mucosal inflammation.

Antibiotic and probiotic agents have increasingly moved in the focus of basic and clinical research as well as clinical trials for IBD therapy. Both approaches modulate the intestinal flora, the former through eradication or reduction, the latter through establishment or increase of luminal bacteria. Although clinical trials provide proof of principle that both approaches can be therapeutically successfull, we just start to understand the mechanims and may get a first feeling for the potential and limitations of these "microbial" therapies.

Mucosal FOXP3+ regulatory T cells are numerically deficient in acute and chronic GvHD.

CD4+CD25+ regulatory T cells (Tregs) control immune responses to self- and foreign antigens and play a pivotal role in autoimmune diseases, infectious and noninfectious inflammation, and graft rejection. Since recent experimental studies have indicated that Tregs were able to ameliorate graft-versus-host disease (GvHD), we analyzed the number of infiltrating Tregs in the intestinal mucosa as one site of GvH reactivity using immunoenzymatic labeling to enumerate FOXP3+ T cells in 95 intestinal biopsies from 49 allografted patients in comparison with healthy controls and patients with infectious inflammation. While patients with cytomegalovirus (CMV)-colitis or diverticulitis showed a concomitant increase of CD8+ effectors and Tregs, acute and chronic GvHD were characterized by the complete lack of a counter-regulation indicated by a FOXP3+/CD8+ T-cell ratio identical to healthy controls.

Peripheral and intestinal regulatory CD4+ CD25(high) T cells in inflammatory bowel disease.

Background & Aims: Regulatory CD25+ T cells (T(reg)) are effective in the prevention and down-regulation of inflammatory bowel disease (IBD) in animal models. Functional T(reg) cells are characterized by the expression of the transcription factor FOXP3 and show a CD4+ CD25(high) phenotype in humans. The aim of this study was to determine whether disease activity in IBD correlates with changes in frequency of T(reg) cells and their distribution in the intestinal mucosa.

[Severe erythrodermic psoriasis in a patient with 22q11 deletion syndrome].

Background: Erythrodermic psoriasis is a severe manifestation of psoriasis and can be triggered by several factors.

Case Report: A 35-year-old man was admitted with severe, almost generalized exfoliative, oozing erythrodermic psoriasis, fever, and cramping of hands and legs. He was under systemic treatment with acitretin.

Intestinal flora and mucosal immune responses.

The normal intestinal flora and the mucosal immune system exist in close spatial proximity. A normal structure and function of both very complex systems is required for health and develops in a constant and interactive process. An abnormal host response to the normal intestinal flora leads to chronic intestinal inflammation.

Pancreatic panniculitis in an 88-year-old man with neuroendocrine carcinoma.

Pancreatic panniculitis is a rare complication that occurs in 0.3-3% of patients with pancreatic diseases. Most of the cases reported to date were associated with adenocarcinoma and acute or chronic pancreatitis.

Regional variation of the alphabeta T cell repertoire in the colon of healthy individuals and patients with Crohn's disease.

Clonally expanded T cells might be involved in the pathogenesis of Crohn's disease (CD). To test the impact of CD on the regional distribution of expanded T cells, this study analyzed the T cell receptor beta (TCRB) repertoire within colonic biopsy specimens from 12 CD patients and 6 noninflammatory controls by TCR spectratyping. Migration characteristics of dominant CDR3 bands from different sites of the normal mucosa suggested focal, segmental, or ubiquitous spreading of individual expanded clones.

T cell receptor delta repertoire in inflamed and noninflamed colon of patients with IBD analyzed by CDR3 spectratyping.

Gamma/delta T cells might play an important role in autoimmune conditions like inflammatory bowel disease (IBD). In the present study, we characterized the T cell receptor (TCR)-delta repertoire by complementarity determining region 3 (CDR3) spectratyping in the inflamed and noninflamed mucosa and in the peripheral blood of subjects with Crohn's disease and ulcerative colitis. In contrast to previously published data about alpha/beta T cells, we rarely found oligoclonal expansions of gamma/delta T cells specific only for the inflamed mucosa.