scholarly journals POS0329 GASTROINTESTINAL INVOLVEMENT IN SYSTEMIC SCLEROSIS: PATHOGENETIC ROLE OF GUT MICROBIOME, CYTOKINES AND ADIPOKINES

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 392.1-392
Author(s):  
E. Pigatto ◽  
M. Schiesaro ◽  
M. Caputo ◽  
M. Beggio ◽  
P. Galozzi ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Gut Microbiome ◽  
Serum Levels ◽  
High Serum ◽  
Healthy Population ◽  
Gastrointestinal Involvement ◽  
Degrading Bacteria ◽  
Gi Symptoms ◽  
Low Levels ◽  
The Impact

Background:Gastrointestinal (GI) involvement is very common in patients with Systemic Sclerosis (SSc). The pathophysiology of GI manifestations has not yet been defined. Cell-mediated immunological reactions appear to lead to endothelial damage resulting in fibrosis. The risk of developing malnutrition reinforces the need to better understand GI pathophysiology in these patients.Objectives:The study aimed to evaluate GI symptoms (GIT 2.0) and malnutrition status (MUST) and to determine specific bacterial changes in gut microbiome by investigating the possible presence of positive hot spots in bacterial species in SSc patients and their potential role in the disease progression. We also evaluated serum levels of adipokines and cytokines involved in the pathogenesis of SSc and their role, in addition to gut microbiome, in predicting the onset of GI involvement and malnutrition in SSc patients.Methods:We enrolled 25 scleroderma patients (EULAR/ACR 2013 criteria). UCLA-SCTC GIT 2.0 questionnaire to evaluate GI symptoms and MUST to investigate the risk of malnutrition were used. Gut microbiome was analyzed and the samples were subjected to extraction for the 16S rRNA gene (Earth Microbiome Project and the NIH-Human Microbiome Project). The microbiome was investigated at phenotypic and genotypic level. Serum levels of cytokines and adipokines (adiponectin and leptin) were evaluated by ELISA.Results:79.9% of patients had GERD and 63.5% abdominal distension at GIT 2.0 questionnaires. 48% of patients had moderate risk of malnutrition (MUST=2) and 12% had high risk (MUST=3). Gut microbioma: 19 patients (76%) had low similarity and 11 (44%) low diversity compared to the healthy population. The prevailing enterotypes of gut microbiome was Bacteroides (80%) and Prevotella (20%). The genotypic evaluation showed a reduced concentration of: gluten-digesting (Lactobacillus); lactose-digesting (Faecalibacterium); vitamin K-producing (Enterococcus, Desulfovibrio and Veillonella); acetaldehyde-degrading bacteria. 24 patients (96%) showed a reduction in bacteria devoted to maintaining weight control (Bifidobacterium and Ruminococcus). The patients had an altered intestinal permeability with less mucolytic bacteria (Bacteroides) and reduced production of LPS (Enterobacter and Escherichia). Low levels of butyrate (Eubacterium and Clostridium), acetate and propionate were found for SCFA-producing bacteria. Potentially pathogenic bacteria were also investigated: Salmonella was found in 14 (56%), Klebsiella in 9 (36%) and Enterococcus Faecalis in 3 (12%) patients. 11 (44%) patients had elevated serum levels of IL10 and IL12; 4 (16%) had high value of leptin. Correlation was found in patients who had a reduced concentration of gluten-digesting bacteria and MUST. Elevated MUST was correlated with serological increase in IL17A and IFN-α. Serum levels of IL12 and IL10 were found to correlate with specific bacteria alterations: high concentration of acetaldehyde-producing bacteria and low levels of acetaldehyde-degrade bacteria (also correlated with high serum levels of IL6), mucolytic bacteria and producers of hydrogen sulphide, acetate and propionate. Finally, reduced levels of mucolytic bacteria and acetate producing bacteria correlated with high serum leptin levels.Conclusion:The relationship between the gut microbiome and SSc seems to be multifactorial. In our study genotypic changes of gut microbioma might play a role in damaging the permeability of the mucosa and increasing risk of malnutrition. The evaluation of gut microbiome and cytokine profile is probably going to be of value in the follow-up of SSc. However, further studies are needed to clarify the impact of GI dysbiosis on the immune system in SSc.References:[1]Patrone V. et al. Gut microbiota profile in systemic sclerosis patients with and without clinical evidence of gastrointestinal involvement, Sci Rep. 2017; 7: 14874Disclosure of Interests:None declared

scholarly journals AB0165 THE ROLE OF CXCL4, CXCL8 AND GDF-15 IN SYSTEMIC SCLEROSIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1382.2-1383
Author(s):  
J. E. Oller Rodriguez ◽  
E. Grau García ◽  
R. Gonzalez Mazario ◽  
M. De la Rubia Navarro ◽  
C. Pávez Perales ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Disease Activity ◽  
Serum Levels ◽  
Pulmonary Involvement ◽  
High Serum ◽  
Complement C3 ◽  
Healthy Population ◽  
Healthy Controls ◽  
Skin Involvement ◽  
Cross Sectional

Background:Systemic Sclerosis (SSc) is an autoinmune disease that can affect several organs and its mortality is fundamentally related to its pulmonary involvement.It is mandatory to seek for biomarkers that help us with early diagnosis and that are also useful for predicting organic involvement, so that we can adjust the diagnostic and therapeutic approach.Objectives:Our aim was to check if the presence of CXCL4, CXCL8 and GDF-15 is greater in the disease than in healthy population, and also their involvement in organic damage.Methods:Observational and cross-sectional study, with a prospectively performed protocol, of patients diagnosed of SSc according to ACR/EULAR 2013 criteria. Demographic, clinical, analytical, activity (EUSTAR index), severity (Medsger scale and modified Rodnan index), health perception (SF36) and disability (HAQ and Cochin test) variables were collected. Moreover, Videocapillaroscopy (VCL) and Respiratory Function Test were made, as well High Resolution Lung Tomography and Echocardiography in order to describe pulmonary features. Serum levels of CXCL4, CXCL8 and GDF-15 were measured in SSc patients and in healthy controls.Results:A total of 42 patients (95.4% women) were included, with an average age of 59.2 years. The median of years since diagnosis was 4, by 6 since the first non-Raynaud symptom. 20 patients were diagnosed with limited SSc, 20 patients diffusely and 2 patients with SSc without scleroderma. 42 healthy controls were also included.We found significantly higher levels of GDF-15 in patients with SSc (P<0.001), without significant differences in CXCL4 and CXCL8 levels between patients with SSc and healthy controls.The presence of GDF-15 was associated with diffuse SSc (P=0.009), pulmonary arterial hypertension (P=0.038), interstitial lung disease (P=0.004), decreased forced vital capacity (FVC), (P=0.002), high serum titles of antiScl70 (P=0.006), increased disease activity measured by EUSTAR index (P=0.001), as with capillary dilations in Capillaroscopy (P=0.015).Moreover, we found an association between CXCL4 levels and the consumption of complement C3 fraction (P=0.008) and skin involvement (higher Rodnan modified score), (P = 0.001); not finding association with lung involvement or other features (spirometric or analytical changes, capillaroscopy or functional tests).Attending to CXCL8, it was associated to consumption of the C4 fraction of complement (P=0.013) and the presence of tortuosities in capillaroscopy (P=0.02) with no other significant findings.Conclusion:The presence of GDF-15 is associated with diffuse SSc, lung impairment, disease activity and changes in capillaroscopy. In addition, CXCL4 was only associated with skin involvement, while CXCL8 was not related to any organic damage in our patients.Disclosure of Interests:None declared

scholarly journals SAT0296 SERUM LEPTIN LEVELS IN SYSTEMIC SCLEROSIS PATIENTS WITH ELECTROCARDIOGRAPHIC ABNORMALITIES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1093.1-1093
Author(s):  
G. Pellegrino ◽  
K. Stefanantoni ◽  
F. Facioni ◽  
C. Angelelli ◽  
A. Gigante ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Chronic Diseases ◽  
Cardiac Fibrosis ◽  
Serum Levels ◽  
High Serum ◽  
Control Group ◽  
Pathologic Finding ◽  
Serum Leptin ◽  
Ecg Abnormalities

Background:Electrocardiographic (ECG) abnormalities are described in 25-75% Systemic Sclerosis (SSc) cases and they are associated with other systemic manifestations as well as with a worse prognosis. There is an increasing need for clinical and laboratory biomarkers to ameliorate the diagnostic and therapeutic approaches to patients with ECG abnormalities, due to their actual low sensitivity and specificity. Adipokines are circulating proteins that appear dysregulated in SSc and leptin in particular is synthesized in response to inflammatory conditions and seems to play a proinflammatory and pro-fibrotic action in SSc. Interesting, many studies in the last years have underlined its role in the cardiac remodeling mechanisms and in the development of cardiac fibrosis in other chronic diseases.Objectives:Aim of our study is to evaluate the role of leptin in the development of cardiac rhythm disorders (CRD) during SSc. Furthermore, by the analysis of the clinical and demographical parameters of our SSc patients, we tried to define other possible features associated with increased serum leptin concentration.Methods:We included eighty-five SSc patients, fulfilling the 2013 ACR/EULAR classification criteria, attending the Regional Rare Disease Center of Policlinico Umberto I of Rome. Fifty presented significant CRD at non-invasive diagnostic techniques (12 Lead ECG, 24-hour Holter ECG). Demographic, clinical, conventional cardiovascular risk factors were examined; instrumental and laboratory assessments were obtained, together with ECG recordings. Thirty-five SSc patients without pathologic finding at ECG traces, matched for demographic and clinical features, were recruited as the control group. In all cases, after obtaining written informed consent, blood samples were taken to measure serum levels of leptin using an ELISA assay (Life Technologies-Italia).Results:The fifty SSc patients with CRD (mean age 51±15 years; F:M 41:9) had pulmonary fibrosis (PF) in 32 cases (64%) and a BMI >25Kg/m2in 22 (44%) while in the control group of thirty-five SSc patients (mean age 49±16 years; F:M 33:2) PF was found in 15 (43%) and a BMI >25Kg/m2in 9 (35%); We detected significantly higher median values of serum leptin in SSc patients with CRD compared to the control group (12027 pg/ml IQR 12314 versus 6392 pg/ml IQR 7103;p 0,0009). Additionally, SSc patients with a BMI> 25 kg/m2(31 cases) as well as those with PF (47 cases) showed a significantly higher median serum leptin levels compared to those with BMI <25 kg/m2(13161 pg/ml IQR 13610 versus 8187 pg/ml IQR 8255;p 0,0008) and those without PF (11740 pg/ml IQR 11940 versus 7616 pg/ml IQR 7855;p 0,0079).Conclusion:To our knowledge this is the first report on high serum levels of leptin in SSc patients with CRD that also confirms its increase in those cases with a BMI >25 kg/m2and with PF, according to scientific literature data. The role of leptin in the pathogenesis of SSc remains unclear although it is already known its involvement in the development of cardiac fibrosis during other chronic diseases. On the basis of these results we speculate on leptin involvement in the pathogenesis of CRD during SSc, although further studies are needed with larger cohort of patients.References:[1]Vacca A et al. Rheumatology, 2014[2]Tyndall AJ et al. Ann Rheum Dis, 2010[3]Muresan L et al. Iran J Pub Health, 2017[4]Sanna T et al. Indian Pacing Electrophysiol J, 2009[5]Riccieri V et al. Clin Exp Rheumatol, 2011[6]Żółkiewicz J et al. Arch Dermatol Res, 2019[7]Huby AC et al. Circulation, 2015[8]Shulze PC et al. Clin Chim Acta, 2005[9]Van de Hoogen F et al. Arthritis Rheum, 2013[10]Gui X et al. Biochem Biophys Res Commun, 2018Disclosure of Interests:Greta Pellegrino: None declared, Katia Stefanantoni Consultant of: ItalfarmacoBoehringer Ingelheim, Fausta Facioni: None declared, Carlotta Angelelli: None declared, Antonietta Gigante: None declared, Roberto Badagliacca: None declared, Carmine Dario Vizza: None declared, Sergio Morelli: None declared, Edoardo Rosato: None declared, Valeria Riccieri: None declared

scholarly journals A Versatile Macromer-Based Glycosaminoglycan (sHA3) Decorated Biomaterial for Pro-Osteogenic Scavenging of Wnt Antagonists

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1037
Author(s):  
Mathis Gronbach ◽  
Franziska Mitrach ◽  
Stephanie Möller ◽  
Sandra Rother ◽  
Sabrina Friebe ◽  
...  
Keyword(s):  
Serum Levels ◽  
Bone Defects ◽  
High Serum ◽  
Qualitative And Quantitative Analysis ◽  
Negative Effects ◽  
Bone Defect Healing ◽  
2D System ◽  
Surface Decoration ◽  
The Impact ◽  
Regeneration Of Bone

High serum levels of Wnt antagonists are known to be involved in delayed bone defect healing. Pharmaceutically active implant materials that can modulate the micromilieu of bone defects with regard to Wnt antagonists are therefore considered promising to support defect regeneration. In this study, we show the versatility of a macromer based biomaterial platform to systematically optimize covalent surface decoration with high-sulfated glycosaminoglycans (sHA3) for efficient scavenging of Wnt antagonist sclerostin. Film surfaces representing scaffold implants were cross-copolymerized from three-armed biodegradable macromers and glycidylmethacrylate and covalently decorated with various polyetheramine linkers. The impact of linker properties (size, branching) and density on sHA3 functionalization efficiency and scavenging capacities for sclerostin was tested. The copolymerized 2D system allowed for finding an optimal, cytocompatible formulation for sHA3 functionalization. On these optimized sHA3 decorated films, we showed efficient scavenging of Wnt antagonists DKK1 and sclerostin, whereas Wnt agonist Wnt3a remained in the medium of differentiating SaOS-2 and hMSC. Consequently, qualitative and quantitative analysis of hydroxyapatite staining as a measure for osteogenic differentiation revealed superior mineralization on sHA3 materials. In conclusion, we showed how our versatile material platform enables us to efficiently scavenge and inactivate Wnt antagonists from the osteogenic micromilieu. We consider this a promising approach to reduce the negative effects of Wnt antagonists in regeneration of bone defects via sHA3 decorated macromer based macroporous implants.

scholarly journals The association of low serum salivary and pancreatic amylases with the increased use of lipids as an energy source in non-obese healthy women

2020 ◽  
Author(s):  
Kei Nakajima ◽  
Ryoko Higuchi ◽  
Taizo Iwane ◽  
Ayaka Iida
Keyword(s):  
Energy Production ◽  
Serum Levels ◽  
Glycated Haemoglobin ◽  
High Serum ◽  
Hydroxybutyric Acid ◽  
Acetoacetic Acid ◽  
Close Relationship ◽  
Low Levels ◽  
Low Serum ◽  
Hba1c Levels

Abstract OBJECTIVE: It is unknown whether low serum levels of salivary and pancreatic amylases are associated with the high combustion of carbohydrates or lipids for energy. Elevated blood ketones and a low respiratory quotient (RQ) can reflect the preferential combustion of lipids relative to carbohydrates. Therefore, using the data from our previous study, we investigated if low levels of serum amylases were associated with a high serum ketone level and low RQ in 60 healthy non-obese young women aged 20–39 years old.RESULTS: Serum ketones [3-hydroxybutyric acid (3-HBA) and acetoacetic acid (AA)] were inversely correlated with RQs, but not body mass index (BMI) or glycated haemoglobin (HbA1c) levels. Logistic regression analysis showed that high levels of serum ketones (3-HBA ≥ 24 μmol/L and AA ≥ 17 μmol/L) and a low RQ (< 0.766) were significantly associated with low serum salivary (< 60 U/L) and pancreatic (< 29 U/L) amylase levels, respectively. These associations were not altered by further adjustments for age, BMI, HbA1c, and estimated glomerular filtration rate. These results confirm the high combustion of lipids for energy in individuals with low serum amylase levels, suggesting a close relationship between circulating amylases and internal energy production.

scholarly journals Serum IGFBP-2 in Systemic Sclerosis as a Protective Factor of Lung Dysfunction

2020 ◽  
Author(s):  
Julien Guiot ◽  
Makon-Sébastien Njock ◽  
Béatrice André ◽  
Fanny Gester ◽  
Monique Henket ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Pulmonary Function ◽  
Lung Disease ◽  
Serum Levels ◽  
Lung Fibroblasts ◽  
Functional Study ◽  
Lung Dysfunction ◽  
The Impact

Abstract Background: Systemic sclerosis (SSc) is a rare connective tissue disease associated with rapid evolving interstitial lung disease (SSc-ILD), driving its mortality. Specific biomarkers associated with the progression of this lung disease are highly needed. We aimed to identify specific biomarkers of SSc-ILD to predict the evolution of the disease.Methods: We compared prospectively serum levels of several biomarkers associated with lung fibrosis in SSc patients (n=102), among which SSc-no ILD (n=63) and SSc-ILD (n=39), compared to healthy subjects (HS) (n=39). We also performed a longitudinal study in a subgroup of 28 patients analyzing biomarkers variations and pulmonary function tests over a period of 2 years. Furthermore, we performed in vitro analysis to study the impact of Insulin like Growth Factor Binding Protein (IGFBP)-2 on fibrotic activity of human lung fibroblasts. Results: Serum levels of IGFBP-1, IGFBP-2, interleukin-8 and matrix metallopeptidase-9 were significantly increased in SSc patients compared to HS while IGF-1 and IGFBP-3 were reduced. The variation of IGFBP-2 between baseline and 2-year follow-up was positively correlated with pulmonary function (assessed by carbon monoxide transfer coefficient (KCO)) at 2-year follow-up (r=0.6, p<0.001). Receiver operating characteristic curve analysis enabled us to identify that baseline IGFBP-2<105 ng/ml was associated with a better outcome (low risk to display KCO<70% predicted) at 2-year follow-up (area under the curve=0.75 at 75% sensibility and 68% specificity, p<0.05). In vitro functional study showed that IGFBP-2 significantly reduced fibroblast proliferation and pro-fibrotic activity.Conclusions: We showed for the first time that serum levels of IGFBP-2 might predict the evolution of SSc-ILD. Baseline IGFBP-2 above 105 ng/ml might be a prognostic factor of alveolo-capillary dysfunction.

scholarly journals The association of low serum salivary and pancreatic amylases with the increased use of lipids as an energy source in non-obese healthy women

2020 ◽  
Author(s):  
Kei Nakajima ◽  
Ryoko Higuchi ◽  
Taizo Iwane ◽  
Ayaka Iida
Keyword(s):  
Energy Production ◽  
Serum Levels ◽  
Glycated Haemoglobin ◽  
High Serum ◽  
Hydroxybutyric Acid ◽  
Acetoacetic Acid ◽  
Close Relationship ◽  
Low Levels ◽  
Low Serum ◽  
Hba1c Levels

Abstract OBJECTIVE It is unknown whether serum levels of salivary and pancreatic amylases are associated with the high combustion of carbohydrates or lipids for energy. Elevated blood ketones and a low respiratory quotient (RQ) can reflect the preferential combustion of lipids relative to carbohydrates. Therefore, we investigated if low levels of serum salivary and pancreatic amylases were associated with a high serum ketone level and low RQ in healthy people. RESULTS Using the data from our previous study, we reanalysed clinical parameters, including serum salivary and pancreatic amylases, serum 3-hydroxybutyric acid (3-HBA) and acetoacetic acid (AA), and RQ in 60 healthy non-obese young women aged 20–39 years old. Serum ketones were inversely correlated with RQs, but not body mass index (BMI) or glycated haemoglobin (HbA1c) levels. Logistic regression analysis showed that high levels of serum ketones and a low RQ were significantly associated with low serum salivary (<60 U/L) and pancreatic (<29 U/L) amylase levels. These associations were not altered by further adjustments for age, BMI, HbA1c, and estimated glomerular filtration rate. These results confirm the high combustion of lipids for energy in individuals with low serum amylase levels, suggesting a close relationship between circulating amylases and internal energy production.

scholarly journals SERUM ANTIGLIADIN ANTIBODIES IN EGYPTIAN CHILDREN WITH AUTISM SPECTRUM DISORDER: RELATIONSHIP TO GASTROINTESTINAL SYMPTOMS, BEHAVIORAL AND SOCIAL COMMUNICATIONS

2018 ◽  
Vol 11 (4) ◽  
pp. 355
Author(s):  
Inas R El-alameey ◽  
Hanaa H Ahmed ◽  
Ihab M Eid ◽  
Ghada El-dory ◽  
Manal Gameel
Keyword(s):  
Autism Spectrum Disorder ◽  
Gastrointestinal Symptoms ◽  
Children With Autism ◽  
Serum Levels ◽  
Autism Spectrum ◽  
High Serum ◽  
Spectrum Disorder ◽  
Gliadin Antibodies ◽  
Gi Symptoms ◽  
Egyptian Children

 Objectives: Gastrointestinal symptoms are major characteristic in children with autism spectrum disorder (ASD), drawing attention to a potent association with gluten sensitivity. The goal of this study was to evaluate anti-gliadin antibodies serum levels in a group of Egyptian children with ASDs and to address the potential link to gastrointestinal (GI) symptoms, behavioral, and social communications.Patients and Methods: This descriptive case–control study included 45 children diagnosed as ASD according to Diagnostic and Statistical Manual of Mental Disorders 5th Edition and a history of GI symptoms, compared with 45 apparently healthy children of matched age and sex. Serum anti-gliadin antibodies were measured using enzyme-linked immunosorbent assay kits.Results: Serum levels of IgM, IgA, and IgG class antibodies to gliadin showed a significant increase compared to healthy controls (p<0.000). Multiple logistic regression analysis showed a significant association between the high serum levels of IgA and IgM class antibodies to gliadin in the studied patients and GI symptoms (p<0.05). A significant association was detected between the high serum levels of IgG antibodies to gliadin and the behavior symptoms (p<0.05).Conclusions: The anti-gliadin antibody response and its association with GI symptoms indicated the involvement of abnormal immunologic intestinal permeability in affected children. Immune system of some autistic patients could be abnormally triggered by gluten assumption.

scholarly journals High serum levels of YKL‐40 in patients with systemic sclerosis are associated with pulmonary involvement

2005 ◽  
Vol 34 (4) ◽  
pp. 293-297 ◽  
Author(s):  
C. Nordenbæk ◽  
J. S. Johansen ◽  
P. Halberg ◽  
A. Wiik ◽  
C. Garbarsch ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Serum Levels ◽  
Pulmonary Involvement ◽  
High Serum

scholarly journals Biochemistry and Immune Biomarkers Indicate Interacting Effects of Pre- and Postnatal Stressors in Pigs across Sexes

Animals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 987
Author(s):  
Haley E. Rymut ◽  
Laurie A. Rund ◽  
Courtni R. Bolt ◽  
María B. Villamil ◽  
Diane E. Bender ◽  
...  
Keyword(s):  
Prenatal Stress ◽  
Serum Levels ◽  
Saline Group ◽  
Respiratory Syndrome Virus ◽  
Immune Challenge ◽  
Immune Stress ◽  
Maternal Immune Activation ◽  
Immune Biomarkers ◽  
Low Levels ◽  
The Impact

The effects of maternal immune activation (MIA) elicited by a prenatal stressor and postnatal metabolic or immune stressors on chemical and inflammatory biomarkers were studied in male and female pigs. Pigs exposed to MIA elicited by porcine reproductive and respiratory syndrome virus and matching controls were assigned at two months of age to fasting stress, immune stress, or a saline group. The serum levels of over 30 chemistry and immune analytes were studied. Significantly low levels of blood urea nitrogen were detected in females exposed to MIA, while the highest creatinine levels were identified in fasting females exposed to MIA. The levels of interferon gamma and interleukin 8 were highest in pigs exposed to postnatal immune challenge. The profiles suggest that MIA may sensitize pigs to postnatal stressors for some indicators while making them more tolerant of other stressors. Effectiveness of practices to ameliorate the impact of postnatal stressors on the physiology of the pig could be enhanced by considering the prenatal stress circumstances.

scholarly journals Serotonin and tryptophan metabolites, autoantibodies and gut microbiome in APECED

2019 ◽  
Vol 8 (1) ◽  
pp. 69-77
Author(s):  
Emmi Naskali ◽  
Katja Dettmer ◽  
Peter J Oefner ◽  
Pedro A B Pereira ◽  
Kai Krohn ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Exploratory Study ◽  
Serum Levels ◽  
Intestinal Microbiome ◽  
Rrna Gene ◽  
Symptoms Of Depression ◽  
Gi Symptoms ◽  
Autoimmune Polyendocrinopathy ◽  
Tryptophan Metabolites ◽  
Circulating Autoantibodies

Objective Intestinal autoimmunity with gastrointestinal (GI) dysfunction has been shown in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Patients lack entero-endocrine (EE) cells and have circulating autoantibodies (Aabs) against critical enzymes in serotonin (5-HT) biosynthesis. Design We sought to determine the serum levels of 5-HT, tryptophan (Trp) metabolites and L-DOPA in 37 Finnish APECED patients and to correlate their abundance with the presence of TPH and AADC Aabs, GI dysfunction and depressive symptoms. We also performed an exploratory analysis of the gut microbiome. Methods Serum 5-HT, L-DOPA and Trp metabolite levels were determined by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). TPH and AADC Aabs were measured by ELISA. Depression was assessed with a structured RBDI questionnaire. The V3–V4 regions of the bacterial 16S rRNA gene were sequenced for gut microbiome exploration. Results Serum 5-HT levels were significantly decreased (130 ± 131 nmol/L vs 686 ± 233 nmol/L, P < 0.0001) in APECED patients with TPH-1 (±AADC) Aabs compared to controls and patients with only AADC Aabs. Reduced 5-HT levels correlated with constipation. The genus Escherichia/Shigella was overrepresented in the intestinal microbiome. No correlation between serum Trp, 5-HT or l-DOPA levels and the RBDI total score, fatigue or sleep disorders was found. Conclusions This exploratory study found low serum levels of 5-HT to be associated with constipation and the presence of TPH-1 and AADC Aabs, but not with symptoms of depression. Hence, serum 5-HT, TPH1 and AADC Aabs should be determined in APECED patients presenting with GI symptoms.

Sign in / Sign up

Export Citation Format

Share Document