CpG-oligodeoxynucleotides stimulate immunoglobulin A secretion in intestinal mucosal B cells.

Bacterial DNA motifs (such as CpG-oligodeoxynucleotides: CpG-ODN) induce innate immune responses via binding to Toll-like-receptor-9 (TLR-9). In murine intestinal mucosa treatment with CpG-ODN worsens chronic intestinal inflammation, whereas it prevents or ameliorates colitis when given in a prophylactic setting. In tonsils B cells have been reported to express TLR-9, especially after activation. Whether B cells in the human intestinal mucosa also express TLR-9 and whether their function can be influenced by CpG-ODN is, so far, unknown. Mucosal B cells were isolated according to a new protocol from surgical specimens of patients with inflammatory bowel disease and from controls by collagenase digestion followed by magnetic cell sorting using anti-CD19 antibody armed magnetic beads. TLR-9 mRNA and protein expression were quantified by real-time polymerase chain reaction (PCR) and Western blot, respectively. Immunoglobulin A (IgA) secretion was measured by enzyme-linked immunosorbent assay after stimulation of isolated B cells with CpG-ODN, control GpC-ODN or lipopolysaccharide (LPS). Flow cytometric analysis of the isolated lamina propria mononuclear cells showed a purification of 73% (+/-22%) CD19(+) cells. By quantitative reverse transcription-PCR and by Western blot TLR-9 expression in this cell population was evident. IgA secretion was increased significantly by CpG-ODN incubation compared with GpC-ODN and LPS. Compared with unstimulated controls, CpG-ODN up-regulated IgA secretion to 139% (+/-21%). These data demonstrate that CD19(+) mucosal B cells express TLR-9 and secrete increased levels of IgA upon stimulation with CpG-ODN, indicating an additional link between adaptive and innate intestinal immune responses.

High proportion of large genomic deletions and a genotype phenotype update in 80 unrelated families with juvenile polyposis syndrome.

BACKGROUND: In patients with juvenile polyposis syndrome (JPS) the frequency of large genomic deletions in the SMAD4 and BMPR1A genes was unknown. METHODS: Mutation and phenotype analysis was used in 80 unrelated patients of whom 65 met the clinical criteria for JPS (typical JPS) and 15 were suspected to have JPS. RESULTS: By direct sequencing of the two genes, point mutations were identified in 30 patients (46% of typical JPS). Using MLPA, large genomic deletions were found in 14% of all patients with typical JPS (six deletions in SMAD4 and three deletions in BMPR1A). Mutation analysis of the PTEN gene in the remaining 41 mutation negative cases uncovered a point mutation in two patients (5%). SMAD4 mutation carriers had a significantly higher frequency of gastric polyposis (73%) than did patients with BMPR1A mutations (8%) (p<0.001); all seven cases of gastric cancer occurred in families with SMAD4 mutations. SMAD4 mutation carriers with gastric polyps were significantly older at gastroscopy than those without (p<0.001). In 22% of the 23 unrelated SMAD4 mutation carriers, hereditary hemorrhagic telangiectasia (HHT) was also diagnosed clinically. The documented histologic findings encompassed a wide distribution of different polyp types, comparable with that described in hereditary mixed polyposis syndromes (HMPS). CONCLUSIONS: Screening for large deletions raised the mutation detection rate to 60% in the 65 patients with typical JPS. A strong genotype-phenotype correlation for gastric polyposis, gastric cancer, and HHT was identified, which should have implications for counselling and surveillance. Histopathological results in hamartomatous polyposis syndromes must be critically interpreted.

Pericarditis as primary manifestation of Mycobacterium bovis SSP. caprae infection.

A 76-year-old white male presented with progressive malaise, weight loss and dyspnea at rest. Echocardiography revealed a circular pericardial effusion and global hypokinesia. Pericardiocentesis showed a purulent exudate and microbiologic examination revealed Mycobacterium bovis fully sensitive to isoniazid, streptomycin, ethambutol, rifampin, and pyrazinamide. By spoligotyping the isolate could be further differentiated to M. bovis ssp. caprae. Antimycobacterial therapy was initiated but 3 weeks later the patient's circulation and renal function deteriorated and he died with clinical signs of sepsis despite intensive care treatment. Pericarditis is a rare manifestation of tuberculosis and can be fatal even when diagnosed and treated appropriately. In low incidence countries diagnosis is often delayed and even overlooked.

[Chronic anaemia in a patient with hereditary haemorrhagic telangiectasia and juvenile gastric polyposis]. / Chronische Anämie bei hereditärer hämorrhagischer Teleangiektasie und juveniler Polyposis des Magens.

HISTORY: A 52-year-old woman with chronic anaemia presented with recurrent epistaxis, telangiectasias and haemangiomas, suggesting the presence of hereditary haemorrhagic telangiectasia (Osler-Rendu-Weber disease). Moreover, previous investigations had also shown multiple polyps of the stomach. INVESTIGATIONS: A severe microcytic iron deficiency anaemia in combination with hepatic haemangiomas and duodenal angio-dysplasia were detected. Gastrointestinal endoscopy revealed multiple juvenile polyps in the gastric fundus and body, indicating the diagnosis of hereditary haemorrhagic telangiectasia in combination with juvenile polyposis. THERAPY AND COURSE: A gastrectomy was performed because of recurrent gastrointestinal bleeding and the malignant potential of juvenile gastric polyposis. Histopathology confirmed the diagnosis and did not reveal any malignancy. CONCLUSION: The association of hereditary haemorrhagic telangiectasia and juvenile polyposis, as seen in this patient, has been reported repeatedly. A diagnosis of one of the described entities should initiate the screening for evidence of the other one to prevent (life-threatening) complications.