An autochthonous case of cystic echinococcosis in Finland, 2015

Peer reviewe

Antibiotic use and the risk of rheumatoid arthritis: a population-based case-control study

Background: Antibiotic-induced disturbances of the human microbiota have been implicated in the development of chronic autoimmune conditions. This study aimed to assess whether antibiotic use is associated with the onset of rheumatoid arthritis (RA). Methods: A nested case-control study was conducted utilising data from the primary care Clinical Practice Research Datalink (CPRD). Patients with an incident diagnosis of RA were identified (1995–2017). Each case was matched on age, gender, and general practice to ≥ 5 controls without RA. Conditional logistic regression was used to examine previous antibiotic prescriptions and RA onset after controlling for confounding factors. Results: We identified 22,677 cases of RA, matched to 90,013 controls, with a median follow-up of 10 years before RA diagnosis. The odds of developing RA were 60% higher in those exposed to antibiotics than in those not exposed (OR 1.60; 95% CI 1.51–1.68). A dose- or frequency-dependent association was observed between the number of previous antibiotic prescriptions and RA. All classes of antibiotics were associated with higher odds of RA, with bactericidal antibiotics carrying higher risk than bacteriostatic (45% vs. 31%). Those with antibiotic-treated upper respiratory tract (URT) infections were more likely to be RA cases. However, this was not observed for URT infections not treated with antibiotics. Antifungal (OR = 1.27; 95% CI 1.20–1.35) and antiviral (OR = 1.19; 95% CI 1.14–1.24) prescriptions were also associated with increased odds of RA. Conclusion: Antibiotic prescriptions are associated with a higher risk of RA. This may be due to microbiota disturbances or underlying infections driving risk. Further research is needed to explore these mechanisms

Intestinal immune activation in juvenile idiopathic arthritis

Abstract The etiology of juvenile idiopathic arthritis (JIA) is still unknown but genetic and enviromental factors play role in the pathogenesis. The aim of the study was to detect endoscopic and immunohistological changes in the gut in JIA compared with the controls and potential correlation of mucosal immunological activation with clinical activity of JIA. JIA patients (n=26) and negative controls (n=71) suffering from gastrointestinal symptoms without significant gastrointestinal disease were recruited for the study. Positive controls were patients with cows milk protein sensitive enteropathy (n=24). The intraepithelial lymphocytes counts, cytotoxic (granzyme A, B) and gamma/delta T-cell count and HLA-DR antigens were evaluated by using immunohistochemistry and messenger RNA expression levels of important immune mediators were assessed with real time PCR (RT-PCR) from fresh frozen intestinal mucosal samples. In JIA compared with negative controls, there was increased presence of lymphonodular hyperplasia and expression of HLA-DR antigens in abnormal mucosal cites, in crypts of the ileum. These changes were correlating with activity of JIA. In JIA compared with negative controls, there were found elevated granzyme B but decreased cytoprotective heat shock protein expression. The mRNA expression levels of anti- inflammatory mediators like TGFβ, IL10 and transcriptor factor of regulatory T-cells FOXP3, inversely correlated with activity of JIA. In conclusion, patients with JIA suffering from gastrointestinal symptoms display evidence of intestinal mucosal immune activation and there is an association between levels of mucosal immune alteration and clinical activity of JIA. These findings support the hypothesis that there is a link between the intestinal immune system and pathogenesis of juvenile idiopathic arthritis. In order to confirm these findings, more extensive series of JIA patients without gastrointestinal symptoms needs to be examined.Tiivistelmä Lastenreuman tautimekanismi on tuntematon. Geneettiset ominaisuudet ja ympäristötekijät ovat yhteydessä taudin syntyyn. Tutkimuksen tavoitteena oli selvittää, onko suolen limakalvolla endoskooppisia tai immunohistologisia muutoksia enemmän lastenreumassa kuin kontrolleilla, ja että liittyvätkö muutokset niveltaudin aktiivisuuteen. Tutkimukseen otettiin 26 suolioireista lastenreumapotilasta, 76 verrokkia joilla ei ollut autoimmuunisairautta sekä 24 viivästynyttä maitoallergiaa sairastavaa lasta, joille tehtiin suolen tähystystutkimus. Ohutsuolinäytteistä arvioitiin immunohistologisesti solunsisäisten lymfosyyttien, gamma/delta-positiivisten lymfosyyttien sekä sytotoksisten (grantsyymi-A ja -B) lymfosyyttien määrä. Lisäksi määritettiin immunohistologisesti ohutsuolen limakalvon epiteelisolujen HLA-DR- antigeenien ja epiteelisolua suojaavien lämpöshokkiproteiinien ilmenemistä sekä käänteis-PCR-menetelmällä keskeisten välttäjäaineiden lähetti-RNA-tasoja. Tutkimuksessa lastenreumaa sairastavilla esiintyi enemmän suolen imukudoskertymää (lymfonodulaarinen hyperplasia) negatiiviseen verrokkiryhmään nähden sekä HLA-DR antigeenejä epätyypillisellä alueella ohutsuolen loppuosan limakalvon kryptassa. Nämä löydökset olivat yhteydessä lastenreuman aktiivisuuteen. Lastenreumassa oli verrokkeja enemmän sytotoksisia lymfosyyttejä ja vähemmän lämpöshokkiproteiineja. Tulehdusta suojaavat lähetti- RNA-tasot korreloivat käänteisesti lastenreumataudin aktiivisuuteen. Väitöstutkimuksen suolioireisilla lastenreumapotilailla oli suolen limakalvolla muutoksia, jotka sopivat poikkeavaan antigeenien käsittelyyn. Nämä löydökset tukevat hypoteesia, että lastenreumassa suolen limakalvon immunologinen aktivaatio on yhteydessä taudin puhkeamiseen. Jotta tulokset voisi yleistää, tarvittaisiin jatkotutkimus, joka on tehty suolioireettomilla lastenreumapotilailla ja riittävällä otoskoolla

Cow’s milk allergy in infancy and later development of juvenile idiopathic arthritis:a register-based case-control study

Abstract We examined the association between cow’s milk allergy (CMA) and juvenile idiopathic arthritis (JIA). The material for this case-control study was collected from national registers of all children born in Finland between 2000 and 2010 and diagnosed with JIA (n = 1,298) and age-, sex-, and place-matched controls (n = 5,179). We identified 235 children with CMA; 66 of these children also had JIA. A conditional logistic regression analysis was performed to evaluate the association between CMA and JIA and to test whether exposure to antibiotics would be a covariate for this association. In boys (but not in girls), a diagnosis of CMA and the use of hypoallergenic formula in infancy were associated with the later development of JIA (odds ratio = 2.4, 95% confidence interval: 1.6, 3.6). The association was most evident in boys who were diagnosed with JIA before age 3 years or diagnosed with CMA with predominantly gastrointestinal symptoms. There was no statistically significant additive interaction between CMA and antibiotic exposure in the later development of JIA. These associations may reflect impaired maturation of intestinal immunity and integrity in boys with a risk of JIA. Predisposing factors related to JIA pathogenesis seem to display a sex-linked disparity

Gut microbiota-host interactions and juvenile idiopathic arthritis

Abstract Background: Juvenile idiopathic arthritis is the most common form of chronic arthritis in children. There is mounting evidence that the microbiota may influence the disease. Main body: Recent observations in several systemic inflammatory diseases including JIA have indicated that abnormalities in the contents of the microbiota may be factors in disease pathogenesis, while other studies in turn have shown that environmental factors impacting the composition of the microbiota, such as delivery mode and early exposure to antibiotics, affect the risk of chronic inflammatory diseases including JIA. Microbial alterations may predispose to JIA through a variety of mechanisms, including impaired immunologic development, alterations in the balances of pro- versus anti-inflammatory bacteria, and low-grade mucosal inflammation. Additional confirmatory studies of microbiota aberrations and their risk factors are needed, as well as additional mechanistic studies linking these alterations to the disease itself. Conclusions: The microbiota may influence the risk of JIA and other systemic inflammatory conditions through a variety of mechanisms. Additional research is required to improve our understanding of the links between the microbiota and arthritis, and the treatment implications thereof