6 research outputs found
Limakalvon IL-17-immuniteetti tautitiloissa : erityisesti tulehduksellisessa suolistosairaudessa
T cells are CD4 lymphocytes participating in cell-mediated immunity, and play a critical role in immune-mediated diseases. T cells divide further into subclasses such as Th1, Th2, and Th17 that participate in mucosal immunity responses caused by extracellular pathogens and also play a role in autoimmune diseases. Th17 cells produce cytokines called the interleukin-17 family (IL-17). Regulatory CD4+ T cells marked by CD4, CD25, and forkhead box P3 (FOXP3), contribute to maintaining tolerance and regulating immune responses to antigens.
This doctoral thesis studies the role of IL-17 type of immunity in intestinal inflammation in Crohn s disease, ulcerative colitis, celiac disease, and type I diabetes (T1D). In particular, the study explores the balance between effector and regulatory T cells in active and inactive Crohn s disease in adults, as well as in pediatric patients with Crohn s disease and ulcerative colitis. Furthermore, the investigation focuses on the effect of anti-TNF-α treatment on the effector and regulatory T cells in Crohn s disease in adults.
Adult patients with Crohn s disease had higher numbers of intestinal IL-17+ and FOXP3+ cells than did control subjects, both before and after the anti-TNF-α treat-ment. Intestinal interferon-γ and IL-17 mRNA expression was higher in Crohn s disease and remained elevated after anti-TNF-α treatment, although the treatment improved intestinal balance between IL-17+ effector and regulatory T cells. In Crohn s disease, mRNA expression of IL-17A, IL-6, and FOXP3 was increased. Fecal IL-17 concentration showed increase in patients with active disease. IL-17 enhanced the IL-8 and TNF-α response of the epithelial cell line to lipopolysaccha-ride in vitro. The findings suggest that activation of the IL-17 axis is fundamentally connected to the etiology of Crohn s disease and may represent the basis for the relapsing nature of the disease.
In pediatric patients, IL-17, IL-22, IL-6, and FOXP3+ mRNA up-regulation and increase in the number of IL-17+ and FOXP3+ cells existed in inflammatory bowel disease. Activation of the IL-17/IL-22 axis and up-regulation of FOXP3 occurred both in pediatric Crohn s disease and ulcerative colitis, indicating shared immuno-logical aberrancy.
In pediatric patients with untreated celiac disease, the mucosal expression of IL-17 and FOXP3 transcripts were elevated as compared with TGA-negative reference children, children with potential celiac disease, gluten-free diet-treated children with celiac disease, or children with T1D. Enhanced spontaneous secretion of IL-1ÎČ, IL-6, and IL-17 occurred in biopsy specimens from patients with untreated celiac disease. Activation of anti-apoptotic bcl-2 in IL-17-treated CaCo-2 epithelial cells suggests that IL-17 might be involved in mucosal protection. Up-regulation of IL-17, howev-er, could serve as a biomarker for the development of villous atrophy and active celiac disease.Valkosoluihin kuuluvat T-solut osallistuvat soluvĂ€litteisen vastustuskyvyn rakentamiseen ja toimintaan. CD4-positiiviset lymfosyytit eli auttaja- T-solut jaetaan edelleen alaluokkiin, kuten Th1, Th2 ja Th17. NĂ€mĂ€ tunnistavat elimistöön tulevia taudinaiheuttajia, mutta autoimmuunisairauksissa T-solut voivat kuitenkin vahingoittaa elimistön omia rakenteita. SÀÀtelevĂ€t CD4-positiiviset solut osallistuvat sietokyvyn sĂ€ilyttĂ€miseen ja sÀÀntelevĂ€t immuunivasteita. Solutyyppien tuottamia merkkiaineita tutkimalla voidaan selvittÀÀ eri sairauksissa tai sairauden eri vaiheissa aktiiviset solut. Esimerkiksi Th17-solut tuottavat valkuaisaineita, kuten interleukiini 17:ÀÀ (IL-17). SÀÀtelevien CD-solujen merkkiaineita taas ovat CD4, CD25 ja FOXP3.
TÀssÀ vÀitöskirjatyössÀ tutkittiin IL-17-immuniteetin ja sÀÀtelevien T-solujen merkitystÀ tulehduksellisissa suolistosairauksissa (Crohnin tauti ja haavainen paksusuolitulehdus) sekÀ keliakiassa ja tyypin I diabeteksessa (T1D). LisÀksi Crohnin tautia sairastavien aikuisten nÀytteistÀ selvitettiin TNF-α-salpaajahoidon vaikutusta. IL-17-immuniteettia ja sÀÀtelevien T-solujen merkkiaineita tutkittiin suolen koepaloista immunohistokemiallisin vÀrjÀyksin, ja lÀhetti-RNA:n mÀÀriÀ selvitettiin PCR-tekniikalla. Uloste- ja verinÀytteistÀ tehtiin vastaavia mÀÀrityksiÀ.
Crohnin tautia sairastavien aikuisten suolistossa oli verrokkeja enemmÀn IL-17- ja FOXP3-positiivisia soluja. Aikuisilla IL-17-pitoisuudet olivat kohonneet sekÀ solu- ettÀ lÀhetti-RNA-tasolla niin taudin aktiivisessa kuin oireettomassakin vaiheessa. Tasot pysyivÀt kohonneina myös TNF-α-salpaajahoitoa saaneilla potilailla, vaikka tasapaino suoliston Th17-solujen ja sÀÀtelevien solujen vÀlillÀ parani. Tulokset viittaavat siihen, ettÀ IL-17-solujen aktivoituminen saattaa liittyÀ Crohnin taudin syntyyn ja uusiutumiseen.
Tulehduksellista suolistosairautta sairastavilla lapsillakin nÀhtiin kohonneet IL 17- ja FOXP3-tasot. Vaikka Crohnin tautia ja haavaista paksusuolitulehdusta on pidetty eri Th-solulajeihin liittyvinÀ tauteina, tutkimuksemme perusteella nÀmÀ sairaudet jakavat osin saman, IL-17-soluihin liittyvÀn hÀiriön immuunijÀrjestelmÀssÀ. Lasten hoitamattomaan keliakiaan liittyi Th17-solujen aktivaatio ja sÀÀtelevien T-solujen lisÀÀntyminen. NÀin ei ollut potentiaalista keliakiaa, gluteenittomalla dieetillÀ hoidettua keliakiaa tai tyypin 1 diabetesta sairastavilla lapsilla
Lasten ja nuorten migreeni
· Lasten ja nuorten migreenin esiintyvyys ja ilmaantuvuus ovat lisÀÀntyneet.· Perusterveydenhuollossa on tÀrkeÀÀ selvittÀÀ migreenin taustasyitÀ ja esiintymistÀ.· Migreenin diagnostiikassa tarvitaan lÀÀkÀrin tutkimuksen lisÀksi harvoin muita tutkimuksia.· Lapsen ja nuoren on tÀrkeÀ saada tietoa pÀÀnsÀryn hoito- ja itsehoitokeinoista.· EstolÀÀkitys voidaan aloittaa perusterveydenhuollossa, mikÀli migreenikohtaukset ovat viikoittaisia.</p
Lasten ja nuorten migreeni
Vertaisarvioitu. English summary.· Lasten ja nuorten migreenin esiintyvyys ja ilmaantuvuus ovat lisÀÀntyneet. · Perusterveydenhuollossa on tÀrkeÀÀ selvittÀÀ migreenin taustasyitÀ ja esiintymistÀ. · Migreenin diagnostiikassa tarvitaan lÀÀkÀrin tutkimuksen lisÀksi harvoin muita tutkimuksia. · Lapsen ja nuoren on tÀrkeÀ saada tietoa pÀÀnsÀryn hoito- ja itsehoitokeinoista. · EstolÀÀkitys voidaan aloittaa perusterveydenhuollossa, mikÀli migreenikohtaukset ovat viikoittaisia.Peer reviewe
In Crohn's Disease, Anti-TNF-α Treatment Changes the Balance between Mucosal IL-17, FOXP3, and CD4 Cells
Peer reviewe
Posterior urethral valves and the risk of neurodevelopmental disorders in two FINNISH cohorts
Publisher Copyright: © 2021 The AuthorsBackground: The Posterior Urethral Valve (PUV) is a persistent membrane of the urethra, which causes obstruction in the urogenital tract in boys. To our knowledge, no comprehensive reports have been published on whether PUV is associated to neurodevelopmental disorders. Here, we analyzed a cohort of PUV patients for neurodevelopmental disorders and verified findings in an older cohort. Methods: In a register based study, we reviewed the hospital registries for patients treated for PUV during 1992â2013 to identify those with neurodevelopmental disorders. Primary outcome measure was any neurodevelopmental diagnosis. Secondary outcome measures were specific disorders: ASD; ADHD, intellectual disability, learning disabilities. Birth weight and gestational age were recorded, serum creatinine levels at specific timepoints were noted. We then investigated these variables to see any correlations to neurodevelopmental disorders. We replicated the strategy for verification in an older cohort of PUV-patients, who had been treated in our institute during 1970â1991. Results: We identified 87 patients treated for PUV of which thirteen (15%) had a verified diagnosis of a neurodevelopmental disorder. 2.3% of PUV patients fulfilled criteria of mild intellectual disability (F70.0/F79.0), 9% had ADHD/ADD-spectrum diagnoses (F90.0/F90.9) and 2.3% had learning disabilities (F83/F81.3). 5.7% of patients presented with difficulties in social interactions (F93.89, F94.8). Five patients presented with more than one neurodevelopmental diagnosis. We confirmed these findings in the older cohort of patients, where a verified neurodevelopmental diagnosis was detected in 14% of patients. We identified no statistically significant associations to gestational age, birth weight or creatinine levels of PUV-patients with neurodevelopmental diagnoses as compared to the PUV-patients not diagnosed for neurodevelopmental disorders. Intellectual disability/mental retardation was more prevalent in our material and this association was statistically significant. Discussion: We show, that the prevalence of intellectual disability among PUV patients exceeds the cumulative prevalence in Finland in both cohorts analyzed here. 15% of PUV-patients presented with a diagnosis of a neurodevelopmental disorder. To our knowledge, this is the first study attempting to outline neurodevelopmental disorders among boys with PUV. This study has limitations. It is register based and only diagnoses made at an institute within our hospital district are considered. The PUV-patients may be under closer surveillance than age-matched healthy children, which may lead to an overrepresentation of cases. The patient number is small and the small subsets of patients within each cohort hamper any further statistical analysis. The neurodevelopmental impacts of pediatric general anesthesia remain elusive and may have corollaries which must be kept in mind when interpretating our results. Patients with PUV require close follow-up in a multi-disciplinary manner, not forgetting neurodevelopmental aspects. Attention to intellectual disability is mandatory. Any suspicion of a developmental delay in a patient with PUV warrants further investigation and corresponding interventions. [Table presented]Peer reviewe