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Article ; Online: HLA-G expression correlates with histological grade but not with prognosis in colorectal carcinoma.

Kaprio, Tuomas / Sariola, Hannu / Linder, Nina / Lundin, Johan / Kere, Juha / Haglund, Caj / Wedenoja, Satu

2021 Volume 98, Issue 3, Page(s) 213–217

Abstract: Trophoblast-specific expression of HLA-G induces immune tolerance for the developing fetus. Pathological HLA-G expression later in life might contribute to immune escape of various cancers. We studied the still controversial role of HLA-G in colorectal ... ...

Abstract	Trophoblast-specific expression of HLA-G induces immune tolerance for the developing fetus. Pathological HLA-G expression later in life might contribute to immune escape of various cancers. We studied the still controversial role of HLA-G in colorectal carcinoma (CRC) using the MEM-G/1 antibody and a tissue microarray series of CRC tumors (n = 317). HLA-G expression appeared in 20% of the tumors and showed high intratumoral heterogeneity. HLA-G positivity was associated with better differentiation (p = 0.002) and non-mucinous histology (p = 0.008). However, HLA-G expression alone showed no prognostic value: 5-years disease-specific survival among patients with HLA-G expression was 68.9% (95% CI: 62.7%-75.0%) compared to 74.8% (95% CI: 63.2%-86.3%) among those without expression. These results support a modulatory role of HLA-G in CRC.
MeSH term(s)	Alleles ; Colorectal Neoplasms/diagnosis ; Colorectal Neoplasms/genetics ; HLA-G Antigens/genetics ; Humans ; Prognosis ; Trophoblasts
Chemical Substances	HLA-G Antigens
Language	English
Publishing date	2021-06-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2845111-9
ISSN	2059-2310 ; 2059-2302
ISSN (online)	2059-2310
ISSN	2059-2302
DOI	10.1111/tan.14334
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Article ; Online: Congenital chloride diarrhea and Pendred syndrome: case report of siblings with two rare recessive disorders of SLC26 family genes.

Lindberg, Eva / Moller, Claes / Kere, Juha / Wedenoja, Satu / Anderzén-Carlsson, Agneta

BMC medical genetics

2020 Volume 21, Issue 1, Page(s) 79

Abstract: Background: Congenital chloride diarrhea (CLD; OMIM 214700) is a rare autosomal recessive disorder caused by pathogenic variations in the solute carrier family 26 member A3 (SLC26A3) gene. Without salt substitution, this chronic diarrheal disorder ... ...

Abstract	Background: Congenital chloride diarrhea (CLD; OMIM 214700) is a rare autosomal recessive disorder caused by pathogenic variations in the solute carrier family 26 member A3 (SLC26A3) gene. Without salt substitution, this chronic diarrheal disorder causes severe dehydration and electrolyte disturbances. Homozygous variants in the nearby gene SLC26A4 disrupt anion exchange in the inner ear and the thyroid, causing Pendred syndrome (PDS; OMIM 274600), which is the most frequent form of syndromic deafness. Case presentation: We report an unusual co-occurrence of two rare homozygous mutations in both the SLC26A3 and SLC26A4 genes, causing a rare combination of both CLD and PDS in two siblings. Although the clinical pictures were typical, the combined loss of these anion transporters might modulate the risk of renal injury associated with CLD. Conclusions: Familial presentation of two rare autosomal recessive disorders with loss of function of different SLC26 anion transporters is described. Independent homozygous variants in the SLC26A3 and SLC26A4 genes cause CLD and PDS in siblings, shedding light on co-occurrence of rare recessive traits in the progeny of consanguineous couples.
MeSH term(s)	Chloride-Bicarbonate Antiporters/genetics ; Diarrhea/congenital ; Diarrhea/diagnosis ; Diarrhea/genetics ; Diarrhea/pathology ; Female ; Genes, Recessive/genetics ; Genetic Testing ; Goiter, Nodular/diagnosis ; Goiter, Nodular/genetics ; Goiter, Nodular/pathology ; Hearing Loss, Sensorineural/diagnosis ; Hearing Loss, Sensorineural/genetics ; Hearing Loss, Sensorineural/pathology ; Humans ; Infant ; Metabolism, Inborn Errors/diagnosis ; Metabolism, Inborn Errors/genetics ; Metabolism, Inborn Errors/pathology ; Mutation ; Pedigree ; Pregnancy ; Rare Diseases/diagnosis ; Rare Diseases/genetics ; Rare Diseases/pathology ; Siblings ; Sulfate Transporters/genetics
Chemical Substances	Chloride-Bicarbonate Antiporters ; SLC26A3 protein, human ; SLC26A4 protein, human ; Sulfate Transporters
Language	English
Publishing date	2020-04-15
Publishing country	England
Document type	Case Reports ; Journal Article
ISSN	1471-2350
ISSN (online)	1471-2350
DOI	10.1186/s12881-020-01023-z
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Article ; Online: The role of vision-related problems in fatal road accidents in Finland.

Wedenoja, Juho / Kalsi, Juhani / Salenius, Salla / Parkkari, Kalle / Kaarniranta, Kai / Tervo, Timo

Acta ophthalmologica

2020 Volume 99, Issue 4, Page(s) 427–430

Abstract: Purpose: To evaluate the significance of vision-related problems in fatal motor vehicle accidents (FMVAs) based on a systematic investigation process by multidisciplinary road accident investigation teams (RAITs).: Methods: Retrospective registry- ... ...

Abstract	Purpose: To evaluate the significance of vision-related problems in fatal motor vehicle accidents (FMVAs) based on a systematic investigation process by multidisciplinary road accident investigation teams (RAITs). Methods: Retrospective registry-based study of all FMVAs during the years 2012-2016 in Finland in which driver causing the accident had a valid Finnish driving licence and the operated motor vehicle required having a driving licence. Results: There were a total of 968 FMVAs. In only 1.3% of all the accidents, a vision-related problem was considered to have contributed to the FMVA, while an observational failure of 23.6% was the leading cause of all the FMVAs. Conclusions: Eye-originating vision problems are rarely a causative risk for FMVAs in Finland. Making current visual standards more stringent would unlikely to be effective in FMVA prevention.
MeSH term(s)	Accidents, Traffic/mortality ; Accidents, Traffic/trends ; Adult ; Aged ; Aged, 80 and over ; Automobile Driving/statistics & numerical data ; Female ; Finland/epidemiology ; Follow-Up Studies ; Humans ; Incidence ; Male ; Middle Aged ; Registries ; Retrospective Studies ; Survival Rate/trends ; Time Factors ; Vision Disorders/epidemiology ; Vision Disorders/physiopathology ; Young Adult
Language	English
Publishing date	2020-09-09
Publishing country	England
Document type	Journal Article
ZDB-ID	2408333-1
ISSN	1755-3768 ; 1755-375X
ISSN (online)	1755-3768
ISSN	1755-375X
DOI	10.1111/aos.14616
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Article ; Online: Characteristics of preeclampsia in donor cell gestations.

Ervaala, Attina / Laivuori, Hannele / Gissler, Mika / Kere, Juha / Kivinen, Katja / Pouta, Anneli / Kajantie, Eero / Heinonen, Seppo / Wedenoja, Satu

Pregnancy hypertension

2021 Volume 27, Page(s) 59–61

Abstract: Pregnancies conceived through donor oocytes or sperm show increased risk for preeclampsia. We studied this issue in a preeclampsia case-control cohort (n = 2778), and found overrepresentation of donor cell gestations among women with preeclampsia (14/ ... ...

Abstract	Pregnancies conceived through donor oocytes or sperm show increased risk for preeclampsia. We studied this issue in a preeclampsia case-control cohort (n = 2778), and found overrepresentation of donor cell gestations among women with preeclampsia (14/1627, 0.86%; OR 1.81; 95% CI: 1.07-3.08; P = 0.025) compared to the population data. Moreover, we observed excess of male births from donor cell pregnancies (male-to-female ratio 2.5 vs. 0.97; OR 2.57; 95% CI 1.02-6.36; P = 0.043). Maternal age (36.7 vs. 30.2; P < 0.0001) and preterm deliveries (64% vs. 38%; P = 0.046) distinguished donor cell gestations from other pregnancies with preeclampsia. These results support foreign fetal antigens as modulators of preeclampsia.
MeSH term(s)	Adult ; Case-Control Studies ; Cohort Studies ; Female ; Humans ; Oocyte Donation/adverse effects ; Oocyte Donation/statistics & numerical data ; Pre-Eclampsia/epidemiology ; Pre-Eclampsia/etiology ; Pre-Eclampsia/immunology ; Pregnancy ; Risk Factors ; Sperm Injections, Intracytoplasmic/adverse effects ; Sperm Injections, Intracytoplasmic/statistics & numerical data
Language	English
Publishing date	2021-12-11
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2584464-7
ISSN	2210-7797 ; 2210-7789
ISSN (online)	2210-7797
ISSN	2210-7789
DOI	10.1016/j.preghy.2021.12.005
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Article ; Online: Transcriptomic Profiling of JEG-3 cells using human leiomyoma derived matrix.

Barmaki, Samineh / Al-Samadi, Ahmed / Leskinen, Katarzyna / Wahbi, Wafa / Jokinen, Ville / Vuoristo, Sanna / Salo, Tuula / Kere, Juha / Wedenoja, Satu / Saavalainen, Päivi

Biomaterials and biosystems

2022 Volume 7, Page(s) 100056

Abstract: Oxygen tension varies during placental and fetal development. Although hypoxia drives early trophoblast invasion, low placental oxygen levels during pregnancy show association with pregnancy complications including fetal growth restriction and ... ...

Abstract	Oxygen tension varies during placental and fetal development. Although hypoxia drives early trophoblast invasion, low placental oxygen levels during pregnancy show association with pregnancy complications including fetal growth restriction and preeclampsia. JEG-3 cells are often used as a trophoblast model. We studied transcriptional changes of JEG-3 cells on a uterine leiomyoma derived matrix Myogel. This might be the closest condition to the real uterine environment that we can get for an in vitro model. We observed that culturing JEG-3 cells on the leiomyoma matrix leads to strong stimulation of ribosomal pathways, energy metabolism, and ATP production. Furthermore, Myogel improved JEG-3 cell adherence in comparison to tissue culture treated plastic. We also included PDMS microchip hypoxia creation, and observed changes in oxidative phosphorylation, oxygen related genes and several hypoxia genes. Our study highlights the effects of Myogel matrix on growing JEG-3 cells, especially on mitochondria, energy metabolism, and protein synthesis.
Language	English
Publishing date	2022-06-17
Publishing country	England
Document type	Journal Article
ISSN	2666-5344
ISSN (online)	2666-5344
DOI	10.1016/j.bbiosy.2022.100056
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Article ; Online: Fecal microbiota in congenital chloride diarrhea and inflammatory bowel disease.

Wedenoja, Satu / Saarikivi, Aki / Mälkönen, Jani / Leskinen, Saara / Lehto, Markku / Adeshara, Krishna / Tuokkola, Jetta / Nikkonen, Anne / Merras-Salmio, Laura / Höyhtyä, Miikka / Hörkkö, Sohvi / Haaramo, Anu / Salonen, Anne / de Vos, Willem M / Korpela, Katri / Kolho, Kaija-Leena

PloS one

2022 Volume 17, Issue 6, Page(s) e0269561

Abstract: Background and aims: Subjects with congenital chloride diarrhea (CLD; a defect in solute carrier family 26 member 3 (SLC26A3)) are prone to inflammatory bowel disease (IBD). We investigated fecal microbiota in CLD and CLD-associated IBD. We also tested ... ...

Abstract	Background and aims: Subjects with congenital chloride diarrhea (CLD; a defect in solute carrier family 26 member 3 (SLC26A3)) are prone to inflammatory bowel disease (IBD). We investigated fecal microbiota in CLD and CLD-associated IBD. We also tested whether microbiota is modulated by supplementation with the short-chain fatty acid butyrate. Subjects and methods: We recruited 30 patients with CLD for an observational 3-week follow-up study. Thereafter, 16 consented to oral butyrate substitution for a 3-week observational period. Fecal samples, collected once a week, were assayed for calprotectin and potential markers of inflammation, and studied by 16S ribosomal ribonucleic acid (rRNA) gene amplicon sequencing and compared to that of 19 healthy controls and 43 controls with Crohn's disease. Data on intestinal symptoms, diet and quality of life were collected. Results: Patients with CLD had increased abundances of Proteobacteria, Veillonella, and Prevotella, and lower abundances of normally dominant taxa Ruminococcaceae and Lachnospiraceae when compared with healthy controls and Crohn´s disease. No major differences in fecal microbiota were found between CLD and CLD-associated IBD (including two with yet untreated IBD). Butyrate was poorly tolerated and showed no major effects on fecal microbiota or biomarkers in CLD. Conclusions: Fecal microbiota in CLD is different from that of healthy subjects or Crohn´s disease. Unexpectedly, no changes in the microbiota or fecal markers characterized CLD-associated IBD, an entity with high frequency among patients with CLD.
MeSH term(s)	Biomarkers ; Butyrates ; Crohn Disease/microbiology ; Diarrhea/congenital ; Diarrhea/genetics ; Feces/microbiology ; Follow-Up Studies ; Gastrointestinal Microbiome/genetics ; Humans ; Inflammatory Bowel Diseases/microbiology ; Metabolism, Inborn Errors ; Microbiota ; Quality of Life ; RNA, Ribosomal, 16S/genetics
Chemical Substances	Biomarkers ; Butyrates ; RNA, Ribosomal, 16S
Language	English
Publishing date	2022-06-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0269561
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Article ; Online: Fetal HLA-G mediated immune tolerance and interferon response in preeclampsia.

EBioMedicine

2020 Volume 59, Page(s) 102872

Abstract: Background: Fetal immune tolerance is crucial for pregnancy success. We studied the link between preeclampsia, a severe pregnancy disorder with uncertain pathogenesis, and fetal human leukocyte antigen G (HLA-G) and other genes regulating maternal ... ...

Abstract	Background: Fetal immune tolerance is crucial for pregnancy success. We studied the link between preeclampsia, a severe pregnancy disorder with uncertain pathogenesis, and fetal human leukocyte antigen G (HLA-G) and other genes regulating maternal immune responses. Methods: We assessed sex ratios and regulatory HLA-G haplotypes in population cohorts and series of preeclampsia and stillbirth. We studied placental mRNA expression of 136 genes by sequencing and HLA-G and interferon alpha (IFNα) protein expression by immunohistochemistry. Findings: We found underrepresentation of males in preeclamptic births, especially those delivered preterm or small for gestational age. Balancing selection at HLA-G associated with the sex ratio, stillbirth, and preeclampsia. We observed downregulation of HLA-G, its receptors, and many other tolerogenic genes, and marked upregulation of IFNA1 in preeclamptic placentas. Interpretation: These findings indicate that an evolutionary trade-off between immune tolerance and protection against infections at the maternal-fetal interface promotes genetic diversity in fetal HLA-G, thereby affecting survival, preeclampsia, and sex ratio. We highlight IFNA1 as a potential mediator of preeclampsia and a target for therapeutic trials. Funding: Finnish Medical Foundation, Päivikki and Sakari Sohlberg Foundation, Karolinska Institutet Research Foundation, Scandinavia-Japan Sasakawa Foundation, Japan Eye Bank Association, Astellas Foundation for Research on Metabolic Disorders, Japan Society for the Promotion of Science, Knut and Alice Wallenberg Foundation, Swedish Research Council, Medical Society Liv och Hälsa, Sigrid Jusélius Foundation, Helsinki University Hospital and University of Helsinki, Jane and Aatos Erkko Foundation, Academy of Finland, Finska Läkaresällskapet, Novo Nordisk Foundation, Finnish Foundation for Pediatric Research, and Emil Aaltonen Foundation.
MeSH term(s)	3' Untranslated Regions ; Alleles ; Disease Susceptibility ; Female ; HLA-G Antigens/genetics ; HLA-G Antigens/immunology ; Homozygote ; Humans ; Immune Tolerance ; Interferons/biosynthesis ; Male ; Maternal-Fetal Exchange/immunology ; Odds Ratio ; Placenta/immunology ; Placenta/metabolism ; Pre-Eclampsia/etiology ; Pre-Eclampsia/metabolism ; Pregnancy ; Pregnancy Outcome ; ROC Curve ; Sex Factors ; Sex Ratio
Chemical Substances	3' Untranslated Regions ; HLA-G Antigens ; Interferons (9008-11-1)
Language	English
Publishing date	2020-07-14
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2851331-9
ISSN	2352-3964
ISSN (online)	2352-3964
DOI	10.1016/j.ebiom.2020.102872
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Article ; Online: Congenital chloride diarrhea misdiagnosed as Bartter syndrome.

Eğrıtaş, Odül / Dalgiç, Buket / Wedenoja, Satu

The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology

2011 Volume 22, Issue 3, Page(s) 321–323

Abstract: Congenital chloride diarrhea is the most frequent secretory-type diarrhea during the infantile period in the presence of normal intestinal mucosa. The disease has an autosomal recessive inheritance. Although approximately half of the reported cases to ... ...

Abstract	Congenital chloride diarrhea is the most frequent secretory-type diarrhea during the infantile period in the presence of normal intestinal mucosa. The disease has an autosomal recessive inheritance. Although approximately half of the reported cases to date are from Finland, a much higher incidence has been reported among Arabic people. The defective gene is SLC26A3, which encodes a Na-independent CL/HCO3 exchanger that is expressed primarily in the apical brush border membrane of ileal enterocytes and colonic epithelium. The disease is characterized by dehydration and hypochloremic metabolic alkalosis. Bartter syndrome, cystic fibrosis and pyloric stenosis also lead to similar electrolyte disturbances in the early neonatal period. The diagnosis of congenital chloride diarrhea can be confirmed by measuring the fecal concentration of Cl, which always exceeds 90 mmol/L in patients with normal water and electrolyte balance. Here, we report a patient with congenital chloride diarrhea misdiagnosed as Bartter syndrome until 20 months of age.
MeSH term(s)	Bartter Syndrome/diagnosis ; Consanguinity ; Diagnosis, Differential ; Diagnostic Errors ; Diarrhea/congenital ; Diarrhea/diagnosis ; Diarrhea/therapy ; Humans ; Infant ; Male ; Metabolism, Inborn Errors/diagnosis ; Metabolism, Inborn Errors/therapy
Language	English
Publishing date	2011-06
Publishing country	Turkey
Document type	Case Reports ; Journal Article
ZDB-ID	1340275-4
ISSN	2148-5607 ; 1300-4948
ISSN (online)	2148-5607
ISSN	1300-4948
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Zs.A 4524: Show issues

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Article ; Online: Review article: the clinical management of congenital chloride diarrhoea.

Wedenoja, S / Höglund, P / Holmberg, C

Alimentary pharmacology & therapeutics

2010 Volume 31, Issue 4, Page(s) 477–485

Abstract: Background: Congenital chloride diarrhoea in a newborn is a medical emergency, requiring early diagnostics and treatment to prevent severe dehydration and infant mortality. While most of the 250 cases reported arise from Finland, Poland and Arab ... ...

Abstract	Background: Congenital chloride diarrhoea in a newborn is a medical emergency, requiring early diagnostics and treatment to prevent severe dehydration and infant mortality. While most of the 250 cases reported arise from Finland, Poland and Arab countries, single cases with this autosomal recessive disorder appear worldwide. Such congenital chloride diarrhoea rarity makes diagnosis difficult. Life-long salt substitution with NaCl and KCl stabilizes fluid, electrolyte and acid-base balance diagnosis. When properly treated, the long-term outcome is favourable. Aim: To summarize data on congenital chloride diarrhoea diagnosis, pathophysiology and treatment, and to provide guidelines for both acute and long-term management of congenital chloride diarrhoea. Methods: Data are based on MEDLINE search for 'chloride diarrhoea', in addition to clinical experience in the treatment of the largest known series of patients. Results: Treatment of congenital chloride diarrhoea involves (i) life-long salt substitution; (ii) management of acute dehydration and hypokalaemia during gastroenteritis or other infections; and (iii) recognition and treatment of other manifestations of the disease, such as intestinal inflammation, renal impairment and male subfertility. Conclusions: This review summarizes data on congenital chloride diarrhoea and provides guidelines for treatment. After being a mostly paediatric problem, adult patients constitute a rare challenge for gastroenterologists worldwide.
MeSH term(s)	Adolescent ; Adult ; Alkalosis/etiology ; Antiporters/genetics ; Antiporters/metabolism ; Biological Transport ; Child ; Child, Preschool ; Chloride-Bicarbonate Antiporters ; Chlorides/administration & dosage ; Chlorides/metabolism ; Colon/metabolism ; Colon/physiopathology ; Dehydration/etiology ; Dehydration/therapy ; Diagnosis, Differential ; Diarrhea/congenital ; Diarrhea/diagnosis ; Diarrhea/genetics ; Diarrhea/therapy ; Female ; Fluid Therapy/methods ; Humans ; Hypokalemia/etiology ; Hyponatremia/etiology ; Incidence ; Infant ; Infant, Newborn ; Infertility, Male/etiology ; Inflammatory Bowel Diseases/epidemiology ; Kidney Failure, Chronic/epidemiology ; Male ; Mutation ; Patient Compliance ; Phenotype ; Polyhydramnios/diagnostic imaging ; Polyhydramnios/etiology ; Pregnancy ; Prognosis ; Treatment Outcome ; Ultrasonography
Chemical Substances	Antiporters ; Chloride-Bicarbonate Antiporters ; Chlorides ; SLC26A3 protein, human
Language	English
Publishing date	2010-02-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	639012-2
ISSN	1365-2036 ; 0269-2813 ; 0953-0673
ISSN (online)	1365-2036
ISSN	0269-2813 ; 0953-0673
DOI	10.1111/j.1365-2036.2009.04197.x
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Article ; Online: Fecal microbiota in congenital chloride diarrhea and inflammatory bowel disease

PLoS ONE

2022 Volume 17, Issue 6 June

Abstract: ... healthy controls and 43 controls with Crohn’s disease. Data on intestinal symptoms, diet and quality ...

Abstract	Background and aims Subjects with congenital chloride diarrhea (CLD; a defect in solute carrier family 26 member 3 (SLC26A3)) are prone to inflammatory bowel disease (IBD). We investigated fecal microbiota in CLD and CLD-associated IBD. We also tested whether microbiota is modulated by supplementation with the short-chain fatty acid butyrate. Subjects and methods We recruited 30 patients with CLD for an observational 3-week follow-up study. Thereafter, 16 consented to oral butyrate substitution for a 3-week observational period. Fecal samples, collected once a week, were assayed for calprotectin and potential markers of inflammation, and studied by 16S ribosomal ribonucleic acid (rRNA) gene amplicon sequencing and compared to that of 19 healthy controls and 43 controls with Crohn’s disease. Data on intestinal symptoms, diet and quality of life were collected. Results Patients with CLD had increased abundances of Proteobacteria, Veillonella, and Prevotella, and lower abundances of normally dominant taxa Ruminococcaceae and Lachnospiraceae when compared with healthy controls and Crohn´s disease. No major differences in fecal microbiota were found between CLD and CLD-associated IBD (including two with yet untreated IBD). Butyrate was poorly tolerated and showed no major effects on fecal microbiota or biomarkers in CLD. Conclusions Fecal microbiota in CLD is different from that of healthy subjects or Crohn´s disease. Unexpectedly, no changes in the microbiota or fecal markers characterized CLD-associated IBD, an entity with high frequency among patients with CLD.
Keywords	Life Science
Subject code	610
Language	English
Publishing country	nl
Document type	Article ; Online
ZDB-ID	2267670-3
ISSN	1932-6203
ISSN	1932-6203
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