Effect of pneumococcal conjugate vaccination on nasopharyngeal carriage in children with early onset of acute otitis media - a randomized controlled trial.

Abstract Conclusion: Although children vaccinated with heptavalent pneumococcal conjugate vaccine (PCV) had fewer episodes of acute otitis media (AOM), this trial was unable to prove a simultaneous decrease in nasopharyngeal carriage

Humoral response to Clostridium difficile in inflammatory bowel disease, including correlation with immunomodulatory treatment

Background and Aim: An abnormal immune response to intestinal bacteria has been observed in Crohn’s disease (CD). Clostridium difficile infection incidence and severity are increased in CD, but reports on the humoral response have provided conflicting results. We aimed to shed light on the possible role of C. difficile in CD pathogenesis by paying attention to the influence of immunomodulatory treatment on the humoral response. Methods: A total of 71 consecutive outpatients with CD, 67 with ulcerative colitis (UC), and 121 healthy controls were analyzed for serum IgA and IgG to C. difficile toxins A and B. Results: IgA levels were similar in all study groups. IgG to toxin A was increased similarly in CD and UC (P = 0.02 for both). In contrast, IgG to toxin B was elevated only in CD patients not receiving disease-modifying anti-inflammatory bowel disease drugs (DMAID) (n = 16) (P = 0.0001), while the CD medication subgroup (n = 47) had a level similar to healthy controls. The UC results were not influenced by DMAID treatment. Conclusion: Our findings add support to the idea of a disturbed interaction between intestinal cells and the microbiota being part of the CD disease mechanism. An abnormal immune response to C. difficile toxin B may be a critical component of this interaction.publishedVersio

Primary Sjögren's Syndrome: Studies of DNA damage responses and autoantibodies

Primary Sjögren’s syndrome (SS) is a chronic autoimmune disease of unknown etiology. The disease primarily involves lachrymal and salivary glands, leading to dryness of the eyes and mouth, but a wide spectrum of exocrine and non-exocrine disease manifestations may be seen. A characteristic property of primary SS is the production of autoantibodies directed against intracellular, often DNA/RNA-modifying, proteins. The hypothesis initiating the present studies was that these autoantibodies reflect some alteration of the antigen, causing not only increased immunogenicity but possibly also abnormal DNA/RNA processing, for instance during repair of DNA damage. Accordingly, this thesis was conducted to explore whether an abnormal DNA damage response is involved in the pathogenesis of primary SS. Initially, the mutations formed in a DNA-damaged shuttle vector plasmid repaired and replicated by SS B cell lines were found to include a reduced frequency of multiple point mutations. In a following study of DNA damage-inducible proteins it was observed that protein extracted from peripheral blood lymphocytes exposed to a DNA-damaging agent showed an aberrant DNA-binding pattern as well as autoantigenic reactivity with SS patient serum IgG. DNA-dependent protein kinase (DNA-PK) is a crucial component of both the DNA repair machinery and the V(D)J recombination process creating immune diversity. No significant difference in DNA-PK activity in T cell lines was found between primary SS patients and healthy individuals. In contrast, primary SS patients positive for SS-A/SS-B autoantibodies displayed both an enhanced capacity to phosphorylate a synthetic p53 peptide and an enhanced G1 cell cycle arrest in response to DNA damage. Furthermore, SS-A/SS-B positive primary SS patients also showed a reduced frequency of t(14;18) chromosomal translocations in blood lymphocytes, a mutation thought to be generated by V(D)J recombinase. An additional aim was to investigate whether primary SS patients display antibodies against CD4, and if so, to determine whether a correlation exists between these antibodies and CD4+ T lymphocyte depletion. Anti-CD4 antibodies were detected in 12.6% of the patients and in 0.6% of the healthy individuals, however, no correlation was found between these antibodies and the CD4+ T lymphocytopenia seen in some SS patients. In summary, the present thesis has documented DNA damage response abnormalities in primary SS cells which may be involved in the pathogenesis of this disease

Presymptomatic autoantibodies in Sjögren's syndrome: what significance do they hold for the clinic?

In a number of autoimmune diseases, for example, rheumatoid arthritis and systemic lupus erythematosus, it is known that autoantibodies are present before the clinical onset. Recently we have shown that autoantibodies can be found many years before symptom onset in primary Sjögren's syndrome. This implies that screening for autoantibodies may be used to identify individuals at risk of developing systemic autoimmune disease. Possibly, autoantibody screening may also contribute to detection of incipient malignancy. This concept stems from a novel finding, on scleroderma patients, suggesting that an anti-tumor immune response elicited by a mutated self-antigen will cross-react with the unmodified version of the self-antigen, and thus come to trigger the formation of autoantibodies

Barns upplevelse av delaktighet och samtycke

Purpose : The purpose of this paper is to illustrate children's experience of participation and consent in decisions making in social service. Questions: Did the children experienced that they where participated in the investigation, the decision and the measure that followed? Were the children allowed to take part in the decision about which measure the result of the investigation should be? Did the children accept to take part in the measures that were proposed to them? Method: Qualitative interviews with four children in the ages between seven and thirteen years old and also with there mothers, grandmother and foster carer. Conclusion: The results of the interviews are that no children have been involved in the decision-making. The children were allowed to decide if they wanted to take part of a measure that was proposed to them. All the children have been investigated by the structure of BBiC, Barns Behov i Centrum. In English Children's Needs in focus. Key Words: children's experience, children's participation, children and decisions-making in social service, interviews with children, law an UN Convention on the Rights of the Child

Recent findings shed light on the aetiopathogenesis of Sjogren's syndrome

The systemic clinical picture of SS patients can be traced back to a disposition of many cell types to over-react when confronted with stress stimuli. This will influence basic cellular processes such as apoptosis and acetylcholine receptor signaling. This tissue hyper-reactivity may also explain the observed autoimmune features, and may constitute a major aetiopathogenetic determinant in SS

Increased subpopulations of CD16(+) and CD56(+) blood monocytes in patients with active Crohn's disease

Background: Circulating monocytes may be subdivided according to the presence or absence of the Fc gamma receptor CD16 and the neural cell adhesion molecule CD56. Monocytes classified into these subpopulations Lire characterized by distinct phenotypic and functional features. We hypothesized that patients with active Crohn's disease differ in their peripheral monocyte subpopulations. Methods: Using flow cytometry we investigated the expression of CD 16 and CD56 on circulating monocytes in 11 patients with active Crohn's disease and 11 controls. These monocyte subpopulations were then analyzed for expression of the chemokine receptor fractalkine, CX(3)CR1, and the monocyte chemoattractant protein-1, CCR2. Results: We found a median 3.7-fold increase in the number of CD16(+) monocytes related to the population with high expression of the pattern recognition receptor CD14 compared to that in the controls (P < 0.001). By studying the percentage of monocytes expressing CX(3)CR1, and their relative fluorescence intensity (RFI), we found significant differences, with both the highest percentage and the highest RFI in the CD14(low)CD16(+) subpopulation, whereas the CD14(high)CD16(-) subgroup represented an intermediate population. Inversely, CCR2 expression was highest in the populations with high expression of CD14, whereas the CD14(low)CD16(+) subpopulation showed the lowest percentage and the lowest RFI for CCR2. We found the percentage of CD14(+)CD56(+) monocytes in patients with active Crohn's disease to be increased 2.7 times compared to the controls (P = 0.011). Conclusions: These results show that subsets of peripheral monocytes with a more mature phenotype are expanded in patients with active Crohn's disease

Abnormal DNA damage-inducible protein in cells from Sjogren's syndrome patients

Antinuclear antibodies are commonly found in patients with Sjogren's syndrome. It has been suggested that the development of antinuclear antibodies depends on the activation of the spliceosome and other transcription-related subcellular particles, some of which have recently been shown also to function in DNA-modifying processes, such as DNA repair and V(D)J recombination. These observations add weight to a previously proposed model for the aetiology of Sjogren's syndrome. This includes the abnormal processing of the T-cell receptor and immunoglobulin genes. To test this hypothesis further, the present study on DNA-modifying proteins in Sjogren's syndrome was initiated. Gel-shift experiments using protein extracted from UV-treated Sjogren cells provided evidence of high molecular weight DNA-binding protein in six out of 12 Sjogren patients studied (but not among seven healthy controls). Some Sjogren sera displayed antibodies to protein extracts from cells treated with psoralen plus UVA radiation. These results indicate an abnormal DNA damage-inducible response in Sjogren's syndrome. It may therefore be concluded that alterations in nuclear protein may play a role in the aetiology of Sjogren's syndrome