Browsing by Subject "INFLAMMATORY-BOWEL-DISEASE"

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  • Sartelli, Massimo; Di Bella, Stefano; McFarland, Lynne V.; Khanna, Sahil; Furuya-Kanamori, Luis; Abuzeid, Nadir; Abu-Zidan, Fikri M.; Ansaloni, Luca; Augustin, Goran; Bala, Miklosh; Ben-Ishay, Offir; Biffl, Walter L.; Brecher, Stephen M.; Camacho-Ortiz, Adrian; Cainzos, Miguel A.; Chan, Shirley; Cherry-Bukowiec, Jill R.; Clanton, Jesse; Coccolini, Federico; Cocuz, Maria E.; Coimbra, Raul; Cortese, Francesco; Cui, Yunfeng; Czepiel, Jacek; Demetrashvili, Zaza; Di Carlo, Isidoro; Di Saverio, Salomone; Dumitru, Irina M.; Eckmann, Christian; Eiland, Edward H.; Forrester, Joseph D.; Fraga, Gustavo P.; Frossard, Jean L.; Fry, Donald E.; Galeiras, Rita; Ghnnam, Wagih; Gomes, Carlos A.; Griffiths, Ewen A.; Guirao, Xavier; Ahmed, Mohamed H.; Herzog, Torsten; Kim, Jae Il; Iqbal, Tariq; Isik, Arda; Itani, Kamal M. F.; Labricciosa, Francesco M.; Lee, Yeong Y.; Juang, Paul; Karamarkovic, Aleksandar; Kim, Peter K.; Kluger, Yoram; Leppäniemi, Ari; Lohsiriwat, Varut; Machain, Gustavo M.; Marwah, Sanjay; Mazuski, John E.; Metan, Gokhan; Moore, Ernest E.; Moore, Frederick A.; Ordonez, Carlos A.; Pagani, Leonardo; Petrosillo, Nicola; Portela, Francisco; Rasa, Kemal; Rems, Miran; Sakakushev, Boris E.; Segovia-Lohse, Helmut; Sganga, Gabriele; Shelat, Vishal G.; Spigaglia, Patrizia; Tattevin, Pierre; Trana, Cristian; Urbanek, Libor; Ulrych, Jan; Viale, Pierluigi; Baiocchi, Gian L.; Catena, Fausto (2019)
    In the last three decades, Clostridium difficile infection (CDI) has increased in incidence and severity in many countries worldwide. The increase in CDI incidence has been particularly apparent among surgical patients. Therefore, prevention of CDI and optimization of management in the surgical patient are paramount. An international multidisciplinary panel of experts from the World Society of Emergency Surgery (WSES) updated its guidelines for management of CDI in surgical patients according to the most recent available literature. The update includes recent changes introduced in the management of this infection.
  • Rivas, Manuel A.; Graham, Daniel; Sulem, Patrick; Stevens, Christine; Desch, A. Nicole; Goyette, Philippe; Gudbjartsson, Daniel; Jonsdottir, Ingileif; Thorsteinsdottir, Unnur; Degenhardt, Frauke; Mucha, Soeren; Kurki, Mitja I.; Li, Dalin; D'Amato, Mauro; Annese, Vito; Vermeire, Severine; Weersma, Rinse K.; Halfvarson, Jonas; Paavola-Sakki, Anu Liisa Paulina; Lappalainen, Anne Maarit; Lek, Monkol; Cummings, Beryl; Tukiainen, Taru; Haritunians, Talin; Halme, Leena; Koskinen, Lotta L. E.; Ananthakrishnan, Ashwin N.; Luo, Yang; Heap, Graham A.; Visschedijk, Marijn C.; MacArthur, Daniel G.; Neale, Benjamin M.; Ahmad, Tariq; Anderson, Carl A.; Brant, Steven R.; Duerr, Richard H.; Silverberg, Mark S.; Cho, Judy H.; Palotie, Aarno; Saavalainen, Paivi; Kontula, Kimmo; Farkkila, Martti; McGovern, Dermot P. B.; Franke, Andre; Stefansson, Kari; Rioux, John D.; Xavier, Ramnik J.; Daly, Mark J. (2016)
    Protein-truncating variants protective against human disease provide in vivo validation of therapeutic targets. Here we used targeted sequencing to conduct a search for protein-truncating variants conferring protection against inflammatory bowel disease exploiting knowledge of common variants associated with the same disease. Through replication genotyping and imputation we found that a predicted protein-truncating variant (rs36095412, p.R179X, genotyped in 11,148 ulcerative colitis patients and 295,446 controls, MAF = up to 0.78%) in RNF186, a single-exon ring finger E3 ligase with strong colonic expression, protects against ulcerative colitis (overall P = 6.89 x 10(-7), odds ratio = 0.30). We further demonstrate that the truncated protein exhibits reduced expression and altered subcellular localization, suggesting the protective mechanism may reside in the loss of an interaction or function via mislocalization and/or loss of an essential transmembrane domain.
  • Rautava, Jaana; Gürsoy, Ulvi K.; Kullström, Adrian; Kononen, Eija; Sorsa, Timo; Tervahartiala, Taina; Gürsoy, Mervi (2020)
    The diagnostic accuracy of point-of-care (PoC) applications may be compromised in individuals with additional inflammatory conditions. This cross-sectional study examined the performance of a commercial oral rinse active matrix metalloproteinase-8 (aMMP-8) PoC immunotest in individuals with (n = 47) and without Crohn's disease (CD) (n = 41). Oral rinse collected from the participants was analyzed by the PoC immunotest. Molecular forms and fragments of salivary MMP-8 were detected by western immunoblotting. The sensitivity of the immunotest for periodontitis was 60.0% in the CD group and 90.0% in the control group. The respective specificity was 75.0% and 80.0%. In both groups, clinical diagnosis of periodontitis exhibited a significant association with the immunotest results, however, the odds ratio (OR) was more than ten-fold in controls (OR 54.3, 95% CI: 3.1-953, p = 0.006) in comparison to CD patients (OR 5.2, 95% CI: 1.3-21.6, p = 0.022). According to Western immunoblot results, the immunotest MMP-8 positivity was not related to elevated levels of molecular forms and fragments of MMP-8 in the CD group, as in the control group. The diagnostic accuracy of the aMMP-8 PoC oral rinse immunotest is reduced in CD patients, which may be related to lower levels or undetectable complexes.
  • Hetemaki, Iivo; Jarva, Hanna; Kluger, Nicolas; Baldauf, Hanna-Mari; Laakso, Sini; Bratland, Eirik; Husebye, Eystein S.; Kisand, Kai; Ranki, Annamari; Peterson, Part; Arstila, T. Petteri (2016)
    Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a monogenic autoimmune disease caused by mutations in the AIRE gene. Although mainly an endocrine disease, a substantial fraction of patients have gastrointestinal manifestations. In this study, we have examined the role of anticommensal responses and their regulation. APECED patients had increased levels of Abs against Saccharomyces cerevisiae (p <0.0001) and against several species of commensal gut bacteria, but not against species predominantly associated with other locations. The anticommensal Ab levels did not correlate with gastrointestinal autoantibodies, neutralizing anti-IL-17 or -IL-22 Abs, or gastrointestinal symptoms, although scarcity of the available clinical data suggests that further study is required. However, the anti-S. cerevisiae Ab levels showed a significant inverse correlation with FOXP3 expression levels in regulatory T cells (Treg), previously shown to be dysfunctional in APECED. The correlation was strongest in the activated CD45RO(+) population (rho = 20.706; p <0.01). APECED patients also had decreased numbers of FOXP3(+) cells in gut biopsies. These results show that APECED patients develop early and sustained responses to gut microbial Ags in a pattern reminiscent of Crohn's disease. This abnormal immune recognition of gut commensals is linked to a systemic Treg defect, which is also reflected as a local decrease of gut-associated Treg. To our knowledge, these data are the first to show dysregulated responses to non-self commensal Ags in APECED and indicate that AIRE contributes to the regulation of gut homeostasis, at least indirectly. The data also raise the possibility of persistent microbial stimulation as a contributing factor in the pathogenesis of APECED.
  • Davis-Richardson, Austin G.; Ardissone, Alexandria N.; Dias, Raquel; Simell, Ville; Leonard, Michael T.; Kemppainen, Kaisa M.; Drew, Jennifer C.; Schatz, Desmond; Atkinson, Mark A.; Kolaczkowski, Bryan; Ilonen, Jorma; Knip, Mikael; Toppari, Jorma; Nurminen, Noora; Hyoty, Heikki; Veijola, Riitta; Simell, Tuula; Mykkanen, Juha; Simell, Olli; Triplett, Eric W. (2014)
  • Perazzio, Sandro F.; Allenspach, Eric J.; Eklund, Kari K.; Varjosalo, Markku; Shinohara, Michi M.; Torgerson, Troy R.; Seppänen, Mikko R. J. (2020)
    Behcet's disease (BD) is a heterogeneous multi-organ disorder in search of a unified pathophysiological theory and classification. The disease frequently has overlapping features resembling other disease clusters, such as vasculitides, spondyloarthritides and thrombophilias with similar genetic risk variants, namelyHLA-B*51,ERAP1,IL-10,IL-23R. Many of the BD manifestations, such as unprovoked recurrent episodes of inflammation and increased expression of IL-1, IL-6 and TNF alpha, overlap with those of the hereditary monogenic autoinflammatory syndromes, positioning BD at the crossroads between autoimmune and autoinflammatory syndromes. BD-like disease associates with various inborn errors of immunity, including familial Mediterranean fever, conditions related to dysregulated NF-kappa B activation (egTNFAIP3,NFKB1,OTULIN,RELA,IKBKG) and either constitutional trisomy 8 or acquired trisomy 8 in myelodysplastic syndromes. We review here the recent advances in the immunopathology of BD, BD-like diseases and the NF-kappa B pathway suggesting new elements in the elusive BD etiopathogenesis.
  • Pfaller, Birgit; Yepes-Nuñez, Juan José; Agache, Ioana; Akdis, Cezmi A.; Alsalamah, Mohammad; Bavbek, Sevim; Bossios, Apostolos; Boyman, Onur; Chaker, Adam; Chan, Susan; Chatzipetrou, Alexia; du Toit, George; Jutel, Marek; Kauppi, Paula; Kolios, Antonios; Li, Carmen; Matucci, Andrea; Marson, Alanna; Bendien, Sarah; Palomares, Oscar; Rogala, Barbara; Szepfalusi, Zsolt; Untersmayr, Eva; Vultaggio, Alessandra; Eiwegger, Thomas (2021)
    Abstract Biologicals have transformed the management of severe disease phenotypes in asthma, atopic dermatitis, and chronic spontaneous urticaria. As a result, the number of approved biologicals for the treatment of atopic diseases is continuously increasing. Although atopic diseases are among the most common diseases in the reproductive age, investigations, and information on half-life, pharmacokinetics defining the neonatal Fc receptors (FcRn) and most important safety of biologicals in pregnancy are lacking. Given the complex sequence of immunological events that regulate conception, fetal development, and the intrauterine and postnatal maturation of the immune system, this information is of utmost importance. We conducted a systematic review on biologicals in pregnancy for indications of atopic diseases. Evidence in this field is scare and mainly reserved to reports on the usage of omalizumab. This lack of evidence demands the establishment of a multidisciplinary approach for the management of pregnant women who receive biologicals and multicenter registries for long-term follow-up, drug trial designs suitable for women in the reproductive age, and better experimental models that represent the human situation. Due to the very long half-life of biologicals, pre-conception counseling, and health care provider education is crucial to offer the best care for mother and fetus. This position paper integrates available data on safety of biologicals during pregnancy in atopic diseases via a systematic review with a detailed review on immunological considerations how inhibition of different pathways may impact pregnancy.
  • Toresson, L.; Steiner, J. M.; Razdan, P.; Spodsberg, E.; Olmedal, G.; Suchodolski, J. S.; Spillmann, T. (2018)
    The aim of this study was to compare the efficacies of parenteral and oral cobalamin supplementation protocols in dogs with chronic enteropathies and low cobalamin concentrations. It was hypothesised that both treatments would increase serum cobalamin concentrations significantly. Fifty-three dogs with chronic enteropathies and serum cobalamin concentrations <285 ng/L (reference interval 244-959 ng/L) were enrolled. Dogs were randomised to treatment with either daily oral cobalamin tablets (0.25-1.0 mg cyanocobalamin daily according to body weight) or parenteral cobalamin (0.4-1.2 mg hydroxycobalamin according to body weight). Serum cobalamin concentrations were analysed 28 +/- 5 days and 90 +/- 15 days after initiation of supplementation. After 28 days, all dogs had serum cobalamin concentrations within the reference interval or above. In the parenteral group (n = 26), median (range) cobalamin concentrations were 228 (150-285) ng/L at inclusion, 2107 (725-10,009) ng/L after 28 days and 877 (188-1267) ng/L after 90 days. In the oral group (n = 27), median (range) serum cobalamin concentrations were 245 (150-285) ng/L at inclusion, 975 (564-2385) ng/L after 28 days and 1244 (738-4999) ng/L after 90 days. In both groups, there were significant differences in serum cobalamin concentrations between baseline and 28 days, and between 28 days and 90 days (P <0.001). In conclusion, both parenteral and oral cobalamin supplementation effectively increase serum cobalamin concentrations in dogs with chronic enteropathies and low cobalamin concentrations. (C) 2017 Elsevier Ltd. All rights reserved.
  • Guo, Michael H.; Nandakumar, Satish K.; Ulirsch, Jacob C.; Zekavat, Seyedeh M.; Buenrostro, Jason D.; Natarajan, Pradeep; Salem, Rany M.; Chiarle, Roberto; Mitt, Mario; Kals, Mart; Pärn, Kalle; Fischer, Krista; Milani, Lili; Magi, Reedik; Palta, Priit; Gabriel, Stacey B.; Metspalu, Andres; Lander, Eric S.; Kathiresan, Sekar; Hirschhorn, Joel N.; Esko, Tonu; Sankaran, Vijay G. (2017)
    Genetic variants affecting hematopoiesis can influence commonly measured blood cell traits. To identify factors that affect hematopoiesis, we performed association studies for blood cell traits in the population-based Estonian Biobank using high-coverage whole-genome sequencing (WGS) in 2,284 samples and SNP genotyping in an additional 14,904 samples. Using up to 7,134 samples with available phenotype data, our analyses identified 17 associations across 14 blood cell traits. Integration of WGS-based fine-mapping and complementary epigenomic datasets provided evidence for causal mechanisms at several loci, including at a previously undiscovered basophil count-associated locus near the master hematopoietic transcription factor CEBPA. The fine-mapped variant at this basophil count association near CEBPA overlapped an enhancer active in common myeloid progenitors and influenced its activity. In situ perturbation of this enhancer by CRISPR/Cas9 mutagenesis in hematopoietic stem and progenitor cells demonstrated that it is necessary for and specifically regulates CEBPA expression during basophil differentiation. We additionally identified basophil count-associated variation at another more pleiotropic myeloid enhancer near GATA2, highlighting regulatory mechanisms for ordered expression of master hematopoietic regulators during lineage specification. Our study illustrates how population-based genetic studies can provide key insights into poorly understood cell differentiation processes of considerable physiologic relevance.
  • Kolho, Kaija-Leena; Alfthan, Henrik (2020)
    Objectives Fecal calprotectin is a valued surrogate marker for intestinal inflammation. It has been argued that calprotectin levels are higher in early age than in later life hampering the use of calprotectin in young children. Subjects and methods To study age-related variation, we used data from our laboratory information system on consecutive, unselected fecal calprotectin measurements from 2014 to 2017 in all children aged 0 to 18 years. From each individual, the first measurement was included and repeated measurements were excluded. Fecal calprotectin was quantitated in the major clinical laboratory in southern Finland, HUSLAB with an ELISA kit from Calpro AS (Calpro/Calprolab, Oslo, Norway). Currently, the assay is performed on two automatic pipetting analysers (Dynex DS2, Chantilly, USA) according to the instructions of the manufacturer. Results There were altogether 11,255 fecal calprotectin results from as many children. The median level of fecal calprotectin was 51 mg/kg in infants <1 year of age (95(th)percentile 648 mg/kg;n = 239). This was 3-4-fold higher when compared to yearly age groups from 1 to 10 years (total number of children included 5,691). Across yearly age groups from 11 to 18, the median values varied from 11 to 19 mg/kg (total number of included children 5,325). The proportion of samples above the routine cut-off for an elevated concentration >100 mg/kg increased with increasing age. Conclusions Fecal calprotectin values in children beyond the first year of life are in general low and comparable in children and adolescents.
  • Nieminen, Janne K.; Niemi, Mirja; Sipponen, Taina; Salo, Harri M.; Klemetti, Paula; Färkkilä, Martti Antero; Vakkila, Jukka; Vaarala, Outi (2013)
  • Wacklin, Pirjo; Tuimala, Jarno; Nikkila, Janne; Tims, Sebastian; Makivuokko, Harri; Alakulppi, Noora; Laine, Pia; Rajilic-Stojanovic, Mirjana; Paulin, Lars; de Vos, Willem M.; Matto, Jaana (2014)
  • Aalto, Kristiina; Lahdenne, Pekka; Kolho, Kaija-Leena (2017)
    Background: Patients with juvenile idiopathic arthritis (JIA) on non-steroidal anti- inflammatory drugs (NSAIDs) may experience abdominal pain. In adults, NSAID use has been linked to an increase in fecal calprotectin (FC) levels, a surrogate marker for gut inflammation. In JIA, data on gut inflammation related to drug use is scarce. Methods: JIA patients followed up at the outpatient pediatric rheumatology clinic in Children's Hospital, Helsinki University Hospital, Helsinki, Finland were routinely assessed for FC if they complained about abdominal pain, had an elevated erythrocyte sedimentation rate (ESR) or used NSAIDs on a daily basis. The FC levels were related to the presence of abdominal pain, to ESR, and to the presence of HLA-B27. Results: Of the total group of 90 patients (median age 9.1 years; 45 JIA patients with disease modifying antirheumatic drugs (DMARDs), 25 without DMARD medication, and 20 arthralgia patients as controls), approximately 50% used NSAIDs, of whom 40% complained about abdominal pain. In patients with abdominal pain, one-third had elevated FC values (>100 mu g/g). The FC values, for the most part, declined along with the discontinuation or reduction of NSAIDs and after intensifying the DMARD medication, where after the pain disappeared. In patients with an elevated ESR, the FC values and ESR normalized in parallel. The presence of HLA-B27 was not associated with FC levels. Conclusion: In patients with JIA and abdominal pain, it may be useful to determine the FC when evaluating the need for further gastrointestinal examinations.
  • Hukkinen, Maria; Pakarinen, Mikko Petteri; Merras-Salmio, Laura; Koivusalo, Antti; Rintala, Risto; Kolho, Kaija-Leena (2016)
    Background: Fecal calprotectin (FC) correlates with endoscopic recurrence of Crohn's disease (CD) in adults but has not been studied among children postoperatively. We aimed to analyze whether FC relates with postoperative CD recurrence in children. Methods: Altogether 51 postoperative endoscopies and FC measurements from 22 patients having undergone surgery for CD at age Results: Ileocecal resection (n = 15), small bowel resection (n = 6), or left hemicolectomy (n = 1) was performed at median age of 15.1 (interquartile range 14.4-17.6) years. Following surgery, FC decreased significantly (659 vs. 103 mu g/g, p = 0.001). During median follow-up of 5.7 (4.2-7.7) years, either endoscopic or histological recurrence occurred in 17 patients (77%). FC > 139 mu g/g at time of endoscopy or FC increase of 79 mu g/g compared to first postoperative value was suggestive of endoscopic recurrence (Rutgeerts score i2-i4), while FC > 101 mu g/g or increase of 21 mu g/g indicated histological recurrence. Best accuracy for prediction of recurrence was obtained by combining FC at endoscopy and the postoperative increase of FC. The corresponding AUROC values were 0.74 (95% 0.58-0.89) for endoscopic recurrence whereas 0.81 (95% CI 0.67-0.95) for histological recurrence. Conclusion: FC is a useful surrogate marker of postoperative recurrence also in pediatric CD patients. (C) 2016 Elsevier Inc. All rights reserved.
  • Kerminen, Sini; Martin, Alicia R.; Koskela, Jukka; Ruotsalainen, Sanni E.; Havulinna, Aki S.; Surakka, Ida; Palotie, Aarno; Perola, Markus; Salomaa, Veikko; Daly, Mark J.; Ripatti, Samuli; Pirinen, Matti (2019)
    Polygenic scores (PSs) are becoming a useful tool to identify individuals with high genetic risk for complex diseases, and several projects are currently testing their utility for translational applications. It is also tempting to use PSs to assess whether genetic variation can explain a part of the geographic distribution of a phenotype. However, it is not well known how the population genetic properties of the training and target samples affect the geographic distribution of PSs. Here, we evaluate geographic differences, and related biases, of PSs in Finland in a geographically well-defined sample of 2,376 individuals from the National FINRISK study. First, we detect geographic differences in PSs for coronary artery disease (CAD), rheumatoid arthritis, schizophrenia, waist-hip ratio (WHR), body-mass index (BMI), and height, but not for Crohn disease or ulcerative colitis. Second, we use height as a model trait to thoroughly assess the possible population genetic biases in PSs and apply similar approaches to the other phenotypes. Most importantly, we detect suspiciously large accumulations of geographic differences for CAD, WHR, BMI, and height, suggesting bias arising from the population's genetic structure rather than from a direct genotype-phenotype association. This work demonstrates how sensitive the geographic patterns of current PSs are for small biases even within relatively homogeneous populations and provides simple tools to identify such biases. A thorough understanding of the effects of population genetic structure on PSs is essential for translational applications of PSs.
  • Helavirta, I.; Hyöty, M.; Oksanen, P.; Huhtala, H.; Haapamäki, J.; Aitola, P. (2018)
    Background and Aims: Patients undergoing restorative proctocolectomy have often suffered from active ulcerative colitis which should be remembered when assessing quality of life after operation. The aim of this study was to explore health-related quality of life after restorative proctocolectomy in those with poor or good pouch function and to compare that to patients with active or inactive ulcerative colitis and to the general population. Material and Methods: Altogether, 282 restorative proctocolectomy patients were investigated. The control group comprised 408 ulcerative colitis patients from the local register. Generic 15D and disease-specific inflammatory bowel disease questionnaire health-related quality of life instruments were used. Population-based data were available for 15D. Pouch function was evaluated with oresland score and colitis activity with simple clinical colitis activity index. Results: 15D results showed that patients with good pouch function had health-related quality of life similar to that of the general population. Health-related quality of life with inflammatory bowel disease questionnaire was equally good in patients with good pouch function (n = 131; 70%) and inactive colitis (n = 95; 63%), and equally impaired in patients with poor pouch function (n = 56; 30%) and active colitis (n = 18; 12%). Conclusion: The majority of patients had health-related quality of life comparable to that in general population. Most patients with active ulcerative colitis are likely to improve their health-related quality of life after successful surgery. These findings are important when informing colitis patients about life after surgery.
  • Li, Wei; Li, Yunzhan; Liu, Zehua; Kerdsakundee, Nattha; Zhang, Ming; Zhang, Feng; Liu, Xueyan; Bauleth-Ramos, Tomás; Mäkilä, Ermei; Kemell, Marianna; Ding, Yaping; Sarmento, Bruno; Wiwattanapatapee, Ruedeekorn; Salonen, Jarno; Zhang, Hongbo; Hirvonen, Jouni T.; Liu, Dongfei; Deng, Xianming; Santos, Hélder A. (2018)
    Orally administrable drug delivery vehicles are developed to manage incurable inflammatory bowel disease (IBD), however, their therapeutic outcomes are compromised by the side effects of systemic drug exposure. Herein, we use hyaluronic acid functionalized porous silicon nanoparticle to bridge enzyme-responsive hydrogel and pH-responsive polymer, generating a hierarchical structured (nano-in-nano-in-micro) vehicle with programmed properties to fully and sequentially overcome the multiple obstacles for efficiently delivering drugs locally to inflamed sites of intestine. After oral administration, the pH-responsive matrix protects the embedded hybrid nanoparticles containing drug loaded hydrogels against the spatially variable physiological environments of the gastrointestinal tract until they reach the inflamed sites of intestine, preventing premature drug release. The negatively charged hybrid nanoparticles selectively target the inflamed sites of intestine, and gradually release drug in response to the microenvironment of inflamed intestine. Overall, the developed hierarchical structured and programmed vehicles load, protect, transport and release drugs locally to inflamed sites of intestine, contributing to superior therapeutic outcomes. Such strategy could also inspire the development of numerous hierarchical structured vehicles by other porous nanoparticles and stimuli-responsive materials for the local delivery of various drugs to treat plenty of inflammatory gastrointestinal diseases, including IBD, gastrointestinal cancers and viral infections.
  • Parkkola, Anna; Laine, Antti-Pekka; Karhunen, Markku; Härkönen, Taina; Ryhänen, Samppa J.; Ilonen, Jorma; Knip, Mikael; Finnish Pediat Diabet Register (2017)
    Genetic predisposition could be assumed to be causing clustering of autoimmunity in individuals and families. We tested whether HLA and non-HLA loci associate with such clustering of autoimmunity. We included 1,745 children with type 1 diabetes from the Finnish Pediatric Diabetes Register. Data on personal or family history of autoimmune diseases were collected with a structured questionnaire and, for a subset, with a detailed search for celiac disease and autoimmune thyroid disease. Children with multiple autoimmune diseases or with multiple affected first-or second-degree relatives were identified. We analysed type 1 diabetes related HLA class II haplotypes and genotyped 41 single nucleotide polymorphisms (SNPs) outside the HLA region. The HLA-DR4-DQ8 haplotype was associated with having type 1 diabetes only whereas the HLA-DR3-DQ2 haplotype was more common in children with multiple autoimmune diseases. Children with multiple autoimmune diseases showed nominal association with RGS1 (rs2816316), and children coming from an autoimmune family with rs11711054 (CCR3-CCR5). In multivariate analyses, the overall effect of non-HLA SNPs on both phenotypes was evident, associations with RGS1 and CCR3-CCR5 region were confirmed and additional associations were implicated: NRP1, FUT2, and CD69 for children with multiple autoimmune diseases. In conclusion, HLA-DR3-DQ2 haplotype and some non-HLA SNPs contribute to the clustering of autoimmune diseases in children with type 1 diabetes and in their families.
  • Muszer, Magdalena; Noszczynska, Magdalena; Kasperkiewicz, Katarzyna; Skurnik, Mikael (2015)
    The microorganisms that inhabit humans are very diverse on different body sites and tracts. Each specific niche contains a unique composition of the microorganisms that are important for a balanced human physiology. Microbial cells outnumber human cells by tenfold and they function as an invisible organ that is called the microbiome. Excessive use of antibiotics and unhealthy diets pose a serious danger to the composition of the microbiome. An imbalance in the microbial community may cause pathological conditions of the digestive system such as obesity, cancer and inflammatory bowel disease; of the skin such as atopic dermatitis, psoriasis and acne and of the cardiovascular system such as atherosclerosis. An unbalanced microbiome has also been associated with neurodevelopmental disorders such as autism and multiple sclerosis. While the microbiome has a strong impact on the development of the host immune system, it is suspected that it can also be the cause of certain autoimmune diseases, including diabetes or rheumatoid arthritis. Despite the enormous progress in the field, the interactions between the human body and its microbiome still remain largely unknown. A better characterization of the interactions may allow for a deeper understanding of human disease states and help to elucidate a possible association between the composition of the microbiome and certain pathologies. This review focuses on general findings that are related to the area and provides no detailed information about the case of study. The aim is to give some initial insight on the studies of the microbiome and its connection with human health.
  • Hanifeh, Mohsen; Rajamäki, Minna Marjaana; Syrjä, Pernilla; Mäkitalo, Laura; Kilpinen, Susanne; Spillmann, Thomas (2018)
    Background: Matrix metalloproteinases (MMPs) 2 and 9 are zinc-and calcium-dependent endopeptidases involved in the breakdown and reconstitution of extracellular matrix under both physiological and pathological conditions. Mucosal MMP-2 and -9 activities have been reported to be upregulated in the intestine of humans with inflammatory bowel disease (IBD), and in animal models of IBD. However, their involvement in the pathogenesis of canine chronic enteropathies (CE) is unknown. This study investigated mucosal pro-and active MMP-2 and -9 activities in dogs with CE and healthy dogs using gelatin zymography, and also to determine the association of their activities in dogs with CE with the canine IBD activity index (CIBDAI), histopathologic findings, the clinical outcome, and hypoalbuminemia. Intestinal mucosal samples from duodenum, ileum, colon, and cecum were collected from 40 dogs with CE and 18 healthy Beagle dogs. Results: In dogs with CE, the number of samples positive for mucosal pro-and active MMP-2 was significantly higher in the duodenum (P <0.0001 and P = 0.011, respectively), ileum (P = 0.002 and P = 0.018, respectively), and colon (P <0.0001 and P = 0.002, respectively), compared with healthy controls. Mucosal pro-MMP-9-positive samples in the duodenum and colon were significantly more frequent in dogs with CE than in healthy dogs (P = 0.0004 and P = 0.001, respectively). Despite the presence of mucosal samples positive for active MMP-9 in the intestinal segments of dogs with CE, the difference compared to healthy controls did not reach statistical significance. None of the intestinal mucosal samples in healthy dogs showed gelatinolytic activity corresponding to the control bands of active MMP-2 and -9. Mucosal active MMP-9 activities displayed a significant positive association with the severity of neutrophil infiltration in the duodenum (P = 00.040), eosinophils in the cecum (P = 00.037), and the CIBDAI score for ileum samples (P = 0.023). There was no significant association of pro-and active MMP-2 and -9 levels with the clinical outcome or hypoalbuminemia. Conclusions: This study is the first to demonstrate upregulation of mucosal pro-and active MMP-2 and pro-MMP-9 in the intestine of dogs with CE compared to healthy dogs. The results provide supporting evidence for the possible involvement of MMP-2 and -9 in the pathogenesis of canine CE.