Veerle Somers
Universiteit Hasselt, Biomed, Faculty Member
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The immune response in patients with Coronavirus Disease 2019 (COVID-19) is highly variable and is linked to disease severity and mortality. However, antibody and cytokine responses in the early disease stage and their association with... more
The immune response in patients with Coronavirus Disease 2019 (COVID-19) is highly variable and is linked to disease severity and mortality. However, antibody and cytokine responses in the early disease stage and their association with disease course and outcome are still not completely understood. In this large, multi-centre cohort study, blood samples of 434 Belgian COVID-19 hospitalized patients with different disease severities (ranging from asymptomatic/mild to critically ill) from the first wave of the COVID-19 pandemic were obtained. Baseline antibody and cytokine responses were characterized and associations with several clinical outcome parameters were determined. Anti-spike immunoglobulin (Ig)G and IgM levels were elevated in patients with a more severe disease course. This increased baseline antibody response however was associated with decreased odds for hospital mortality. Levels of the pro-inflammatory cytokines IL-6, IP-10 and IL-8, the anti-inflammatory cytokine IL-1...
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CD4+ CD25high regulatory T cells (Tregs) of patients with relapsing-remitting (RR) multiple sclerosis (MS), in contrast to those of patients with secondary progressive (SP) MS, show a reduced suppressive function. In this study, we... more
CD4+ CD25high regulatory T cells (Tregs) of patients with relapsing-remitting (RR) multiple sclerosis (MS), in contrast to those of patients with secondary progressive (SP) MS, show a reduced suppressive function. In this study, we analysed forkhead box P3 (FOXP3) at the single-cell level in MS patients and controls (healthy individuals and patients with other neurological diseases) by means of intracellular flow cytometry. Our data revealed a reduced number of peripheral blood CD4+ CD25high FOXP3+ T cells and lower FOXP3 protein expression per cell in RR-MS patients than in SP-MS patients and control individuals, which was correlated with the suppressive capacity of Tregs in these patients. Interestingly, interferon (IFN)-β-treated RR-MS patients showed restored numbers of FOXP3+ Tregs. Furthermore, a higher percentage of CD4+ CD25high FOXP3+ Tregs in RR-MS patients, as compared with controls and SP-MS patients, expressed CD103 and CD49d, adhesion molecules involved in T-cell recruitment towards inflamed tissues. This was consistent with a significantly increased number of CD27+ CD25high CD4+ T cells in the cerebrospinal fluid (CSF), as compared with peripheral blood, in RR-MS patients. Taken together, these data show aberrant FOXP3 expression at the single-cell level correlated with Treg dysfunction in RR-MS patients. Our results also suggest that Tregs accumulate in the CSF of RR-MS patients, in an attempt to down-regulate local inflammation in the central nervous system.
Research Interests: Immunology, Immune response, Multiple sclerosis, Flow Cytometry, Autoimmunity, and 15 moreAdolescent, Medicine, Dendritic Cells, Humans, Autoimmune Disease, Female, Male, Central Nervous System, Aged, Middle Aged, Adult, Immunophenotyping, Medicine and Health Sciences, Immune Tolerance, and Lymphocyte Count
BackgroundThere is an unmet need for biomarkers to identify patients with axial spondyloarthritis (axSpA), as clinical manifestations often overlap with other disorders. Previously, we identified immunoglobulin G (IgG) antibodies to 3... more
BackgroundThere is an unmet need for biomarkers to identify patients with axial spondyloarthritis (axSpA), as clinical manifestations often overlap with other disorders. Previously, we identified immunoglobulin G (IgG) antibodies to 3 Hasselt University (UH)-axSpA peptides which could provide a novel tool for diagnosis of a subset of axSpA patients [1].ObjectivesThe aim of this study was to identify novel IgA antibodies in early axSpA patients and to determine their diagnostic potential in combination with previously determined IgG antibodies against UH-axSpA-IgG antigens.MethodsAn axSpA cDNA phage display library constructed from axSpA hip synovium, was used to screen for novel IgA antibodies in plasma from early axSpA patients. The diagnostic value of these antibodies against novel UH-axSpA-IgA and previously identified UH-axSpA-IgG antigens was determined in two independent axSpA cohorts [UH cohort and the Leuven spondyloarthritis biologics cohort (BIOSPAR)], in healthy controls and in patients with chronic low back pain (CLBP) using ELISA.ResultsWe identified antibodies to 7 novel UH-axSpA-IgA antigens, of which 6 correspond to non-physiological peptides and 1 to the human histone deacetylase 3 (HDAC3) protein. IgA antibodies against 2 of these 7 novel UH-axSpA-IgA antigens and IgG antibodies against 2 of 3 the previously identified antigens were significantly more present in axSpA patients from the UH cohort (18/70, 25.7%) and the (Bio)SPAR cohort (26/164, 15.9%), compared to controls with CLBP (2/66, 3%). Antibodies to this panel of 4 antigens were present in 21.1 % (30/142) of patients with early axSpA from the UH and (Bio)SPAR cohorts. The positive likelihood ratio for confirming early axSpA using antibodies to these 4 UH-axSpA antigens was 7.0. So far, no clinical correlation between the novel identified IgA antibodies and inflammatory bowel disease could be identified.ConclusionScreening an axSpA cDNA phage display library for IgA reactivity resulted in the identification of 7 novel UH-axSpA-IgA antigens, of which 2 show promising biomarker potential for the diagnosis of a subset of axSpA patients, in combination with previously identified UH-axSpA-IgG antigens.Reference[1]Quaden D, Vandormael P, Ruytinx P, Geusens P, Corten K, Vanhoof J, et al. Antibodies Against Three Novel Peptides in Early Axial Spondyloarthritis Patients From Two Independent Cohorts. Arthritis Rheumatol. 2020;72(12):2094-105.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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Rheumatoid arthritis (RA) is an inflammatory autoimmune disease in which 30% of patients are seronegative for the two serological RA markers, rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (ACCP). However, both... more
Rheumatoid arthritis (RA) is an inflammatory autoimmune disease in which 30% of patients are seronegative for the two serological RA markers, rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (ACCP). However, both markers also have lower sensitivities in early stages of the disease. The lack of effective biomarkers for this subpopulation of RA patients causes a delayed diagnosis. Therefore, discovery of novel circulating autoantibody biomarkers for these early RF-negative and ACCP-negative RA patients are advance planning of these subsets. 136 enriched antigenic markers were identified by high-throughput screening an RA library with autoantibodies in the sera of RA patients (positive selection) and healthy control (negative selection). Phage-ELISA-based re-screening determined 13 out of 136 enriched antigenic targets in which increased antibody levels rised up. Two of the 13 identified targets, namely special A-T rich DNA binding protein (SATB1) and EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1), which had highest increased antibody levels, were selected for further characterization. Reactivity of serum antibodies against these proteins was tested in a protein ELISA using the sera of 137 RA patients and 159 healthy controls. Autoantibodies against SATB1 were detected with 79% sensitivity and 82% specificity, while 87% sensitivity and 52% specificity were obatained for antibodies directed against EFEMP1. With regard to cytokine assay, interestingly, pro-inflammationary cytokines including TNF (tumour necrosis factor) increased over 1000 pg/ml or IL-4 (interleukin-4) or IL- 13 similarly increased up to 90 pg/ml and 102 pg/ml, respectively for co-culture with anti-SATB1 monoclonal antibody. Under treatment with EFEMP1 mAb resulting IL-1, TNF and IL-4 triggered up to 1300 pg/ml, 1250 pg/ml and 180 pg/ml, respectively. In T cell phenotype characterization, two subsets of CD4 + T cell and CD8 + cell were stimulated and differentiated from peripheral blood mononuclear cells (PBMCs) at 29.7% and 1.2% for anti-SATB mAb; 31.3% and 2.8% for anti-EFEMP1 mAb.
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Research Interests: Chemistry, Multiple sclerosis, Medicine, Gene expression, Cerebrospinal Fluid, and 15 moreGlycation, Individuals, Disease, Neuroinflammation, Microglia, Astrocyte, Central Nervous System, Mechanisms, Choroid Plexus, Astrocytes, Biomarker, Receptor, Oxidation, Methylglyoxal, and Cardiovascular medicine and haematology
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Background The contribution of native or modified oligodendroglia-derived extracellular vesicles (OL-EVs) in controlling chronic inflammation is poorly understood. In activated microglia, OL-EVs contribute to the removal of cytotoxic... more
Background The contribution of native or modified oligodendroglia-derived extracellular vesicles (OL-EVs) in controlling chronic inflammation is poorly understood. In activated microglia, OL-EVs contribute to the removal of cytotoxic proteins following a proteotoxic stress. Intracellular small heat shock protein B8 (HSPB8) sustain this function by facilitating autophagy and protecting cells against oxidative stress mediated cell death. Therefore, secretion of HSPB8 in OL-EVs could be beneficial for neurons during chronic inflammation. However, how secreted HSPB8 contribute to cellular proteostasis remains to be elucidated. Methods We produced oligodendroglia-derived EVs, either native (OL-EVs) or HSPB8 modified (OL-HSPB8-EVs), to investigate their effects in controlling chronic inflammation and cellular homeostasis. We analyzed the impact of both EV subsets on either a resting or activated microglial cell line and on primary mixed neural cell culture cells. Cells were activated by s...
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ABSTRACTA recently found biomarker regarding multiple sclerosis, namely the anti-SPAG16 antibody (Ab), could be a potential way for early detection, prognosis and diagnosis of said autoimmune disease. Merging electrochemical analysis with... more
ABSTRACTA recently found biomarker regarding multiple sclerosis, namely the anti-SPAG16 antibody (Ab), could be a potential way for early detection, prognosis and diagnosis of said autoimmune disease. Merging electrochemical analysis with a microfluidic system is a novel approach, which avoids the use of labelling steps as seen in traditional ELISA immunoassays. In this study, aluminium interdigitated electrodes on polystyrene-coated PET foils were implemented in a microfluidic flow cell to bind and detect SPAG16 Abs by impedimetric measurements. The coated PET foils showed a clear affinity for the fusion protein SPAG16-THIO and thioredoxin (THIO). Determining sensitivity and specificity of antibody-antigen binding using a microfluidic ELISA immunoassay has revealed the test to be unreliable by showing no linear pattern of a dilution series of the standard and producing skewed inconsistent results. The impedimetric analysis showed opposite results of what one would expect. The syste...
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Background:Rheumatoid arthritis (RA) is an autoimmune disorder that is characterized by chronic inflammation of the joint synovium and presence of autoantibodies in most patients. For RA, many treatments are currently available but each... more
Background:Rheumatoid arthritis (RA) is an autoimmune disorder that is characterized by chronic inflammation of the joint synovium and presence of autoantibodies in most patients. For RA, many treatments are currently available but each treatment will only induce disease remission in a subset of patients. Moreover, finding out which patients respond well to first-line therapy with classical synthetic disease modifying anti-rheumatic drugs (csDMARDs), still largely depends on trial and error.Objectives:In this study, we aim to find novel RA autoantibody biomarkers that predict therapy response to csDMARDs before the initiation of treatment.Methods:In the CareRA trial, a Flemish multicenter study of different treatment regimes, serum samples were collected from RA patients that did or did not show disease remission (DAS28(CRP)<2.6) in response to csDMARDs, combined with a step down glucocorticoid treatment. In our study, baseline samples, collected before the start of treatment, we...
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Microglia, the immunocompetent cells of the central nervous system (CNS), play an important role in maintaining cellular homeostasis in the CNS. These cells secrete immunomodulatory factors including nanovesicles and participate in the... more
Microglia, the immunocompetent cells of the central nervous system (CNS), play an important role in maintaining cellular homeostasis in the CNS. These cells secrete immunomodulatory factors including nanovesicles and participate in the removal of cellular debris by phagocytosis or autophagy. Accumulating evidence indicates that specifically the cellular exchange of small extracellular vesicles (EVs), participates in physiology and disease through intercellular communication. However, the contribution of microglial‐derived extracellular vesicles (M‐EVs) to the maintenance of microglia homeostasis and how M‐EVs could influence the phenotype and gene function of other microglia subtypes is unclear. In addition, knowledge of canonical signalling pathways of inflammation and immunity gene expression patterns in human microglia exposed to M‐EVs is limited. Here, we analysed the effects of M‐EVs produced in vitro by either tumour necrosis factor alpha (TNFα) activated or non‐activated micr...
Research Interests: Chemistry, Biology, Cell Biology, Autophagy, Medicine, and 3 moreMicroglia, Wiley, and Extracellular Vesicles
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Present methods for DNA isolation of stool have various limitations such as the amount of stool used, the requirement of lavage fluids or the use of fresh stool. In this paper, a new method is described for the isolation of human nucleic... more
Present methods for DNA isolation of stool have various limitations such as the amount of stool used, the requirement of lavage fluids or the use of fresh stool. In this paper, a new method is described for the isolation of human nucleic acids from stool, which is independent from the moment of collection. Fecal samples as dry as possible were collected from 75 patients; two grams of stool were mixed with a lysis buffer containing phenol. DNA yields of crude stool were variable and ranged from 9–1686 μg/g of feces. With dot blots in 9 of the 75 cases, the human DNA was identified and ranged from 0.06%–46%. In the remaining 66 cases, human genomic DNA was detected by nested PCR, using human K-ras gene amplification as an example. Amplification products were confirmed for human K-ras with the exonuclease-amplification coupled capture technique (EXACCT). In conclusion, the developed DNA isolation method can be used for the study of large numbers of stool samples, is independent of the ...
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Research Interests: Endocrinology, Physical Activity, Medicine, Internal Medicine, Blood Pressure, and 13 moreRenin Angiotensin Aldosterone System, Polymerase Chain Reaction, Polymorphism (computer Science), Leptin, Body Mass Index, Enzyme, Clinical Sciences, Gene Polymorphism, Body mass index (BMI), Angiotensin Converting Enzyme, Young Men, Allele Frequency, and Radioimmunoassay
ABSTRACT Background/Purpose: Recent genome-wide association studies (GWAs) have identified &gt; 30 SNPs predisposing to Rheumatoid Arthritis(RA). These variants are helpful in unraveling the pathogenesis of RA. However, most... more
ABSTRACT Background/Purpose: Recent genome-wide association studies (GWAs) have identified &gt; 30 SNPs predisposing to Rheumatoid Arthritis(RA). These variants are helpful in unraveling the pathogenesis of RA. However, most therapeutic strategies target pathways of disease progression. Genetic factors account for a considerable proportion of variance in joint damage, but thus far only a few replicated severity factors are known and no GWAS has been performed. We aimed to increase the understanding of the processes underlying the inter-individual differences in joint damage in anti-citrullinated peptide anti-bodies (ACPA)-positive RA by performing a 3-staged GWAS on joint damage progression using high-quality radiology data, followed by in vitro and ex vivo studies. Methods: Stage 1 was performed on 385 ACPA-positive RA-patients Methods: Stage 1 was performed on 385 ACPA-positive RA-patients from the NARAC using Illumina HumanHap 550k BeadChips. Stage 2 concerned of 1,567 X-rays of 301 ACPA-positive RA-patients included in a Dutch cohort with 7 years follow-up. In stage 3, 861 X-rays of 742 North-American ACPA-positive RA-patients included in the NDB and Wichita-cohorts were studied. All X-rays were scored using the Sharp-van der Heijde method (ICCs all 0.9). The expression of SPAG16 variants was studied by RT-qPCR using a RA synovium cDNA library and cDNA derived from other RA tissues and fibroblast-like synoviocytes (FLS). Expression levels of MMP1 and MMP3 of FLS before and after stimulation with TNF- (10 ng/ml) and IL1 (1ng/ml) were evaluated by RT-qPCR and ELISA (cell culture supernatants). Finally serum MMP3 levels were measured in RA patients of stage 2 using ELISA. Results: In stage 1, the strongest association was observed for a cluster of SNPs at 2q34, the region of Sperm associated AntiGen16 (SPAG16, P 4.55 10 7, 0.77 fold progression rate per year per minor allele). Independent replication was obtained in stage 2 and 3, again observing a protective effect on damage progression (P 2.16 10 2 and 2.29 10 2 resp.). Apart from its role in spermatozoa, the function of SPAG16 is incompletely known. We detected SPAG16 isoforms in RA tissues and FLS. No relation between expression levels of SPAG16 transcripts in FLS and SPAG16 genotypes could be detected. However, the matrix degrading capacity of FLS may be affected. FLS of patients with the minor allele tended to express less MMP3 mRNA and secreted lower levels of MMP3 (P 2.28 10 2). Also after cytokine stimulation the minor allele was associated with less production of MMP3. Furthermore, RA-patients carrying the minor allele had lower serological levels of MMP3 (P 4.59 10 2) and lower MMP3 levels were associated with less progression of damage(P 3.09 10 3). Conclusion: A genetic variant in SPAG16 is associated with less production of MMP3 by FLS and protection against joint damage progression. These findings indicate a new pathway involved in joint damage in ACPA-positive RA.
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Background The WHO defines different COVID-19 disease stages, where pathophysiological mechanisms differ. Clinical, radiological, histological, microbiological, and immunological characteristics of different COVID-19 disease stages were... more
Background The WHO defines different COVID-19 disease stages, where pathophysiological mechanisms differ. Clinical, radiological, histological, microbiological, and immunological characteristics of different COVID-19 disease stages were evaluated. Methods Forty-four PCR-confirmed COVID-19 patients were included in a prospective minimal invasive autopsy cohort. Patients were classified according to WHO disease classification in mild-moderate (n=4), severe-critical (n=32) and post-acute disease (n=8) and clinical, radiological, histological, microbiological, and immunological data were compared. Results Classified according to Thoracic Society of America, patients with mild-moderate disease had no typical COVID-19 images on CT-Thorax versus 71.9% with typical images in severe-critical disease and 87.5% typical images in post-acute disease (p
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Research Interests: Immunology, Autoimmunity, Medicine, Osteoarthritis, Colorectal cancer, and 15 moreHumans, Internal Medicine, Female, Disease, Rheumatic Heart Disease, Male, Phage display, Expression, Gene, Arthritis, Association, Biological markers, B Lymphocytes, Enzyme Linked Immunosorbent Assay, and Autoantibodies
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Myasthenia Gravis (MG) is an antibody-mediated autoimmune disorder affecting the postsynaptic membrane of the neuromuscular junction (NMJ). MG is characterized by an impaired signal transmission between the motor neuron and the skeletal... more
Myasthenia Gravis (MG) is an antibody-mediated autoimmune disorder affecting the postsynaptic membrane of the neuromuscular junction (NMJ). MG is characterized by an impaired signal transmission between the motor neuron and the skeletal muscle cell, caused by auto-antibodies directed against NMJ proteins. The auto-antibodies target the nicotinic acetylcholine receptor (nAChR) in about 90% of MG patients. In approximately 5% of MG patients, the muscle specific kinase (MuSK) is the auto-antigen. In the remaining 5% of MG patients, however, antibodies against the nAChR or MuSK are not detectable (idiopathic MG, iMG). Although only the anti-nAChR and anti-MuSK auto-antibodies have been demonstrated to be pathogenic, several other antibodies recognizing self-antigens can also be found in MG patients. Various auto-antibodies associated with thymic abnormalities have been reported, as well as many non-MG-specific auto-antibodies. However, their contribution to the cause, pathology and severity of the disease is still poorly understood. Here, we comprehensively review the reported auto-antibodies in MG patients and discuss their role in the pathology of this autoimmune disease.