Papers by Yves Renaudineau
![Research paper thumbnail of [Hepatitis C virus and chronic hepatopathies in Dakar: case-control study]](https://a.academia-assets.com/images/blank-paper.jpg)
Médecine tropicale : revue du Corps de santé colonial, 2000
In Black Africa, the role of hepatitis C virus (HCV) in the onset of chronic hepatic disease is u... more In Black Africa, the role of hepatitis C virus (HCV) in the onset of chronic hepatic disease is unclear. This is particularly true in Senegal where the prevalence of HCV is moderate. To gain insight into this question, a case-control study including 73 patients and 73 controls was carried out at Principal Hospital in Dakar in 1995. The patients included in this study presented chronic hepatitis in 2 cases cirrhosis in 25 and hepatocellular carcinoma in 46. Patients and controls underwent serologic testing for HCV (ELISA screening test followed by 3rd generation ELISA test in case of positive results and confirmation by immunoblot) with determination of HCV serotype using the immunoenzymatic method. Testing also included research for infection by hepatitis B virus and for anti-delta antibodies. Anti-HCV antibodies were detected in two patients (3 p. 100) and serology was suspicious in two others. Serotype 2 was detected in one of these patients. No positive results were recorded in c...
Frontiers in Immunology, 2015
An in silico approach reveals associations between genetic and epigenetic factors within regulato... more An in silico approach reveals associations between genetic and epigenetic factors within regulatory elements in B cells from primary Sjögren's syndrome patients. Recent advances in genetics have highlighted several regions and candidate genes associated with primary Sjögren's syndrome (SS), a systemic autoimmune epithelitis that combines exocrine gland dysfunctions, and focal lymphocytic infiltrations. In addition to genetic factors, it is now clear that epigenetic deregulations are present during SS and restricted to specific cell type subsets, such as lymphocytes and salivary gland epithelial cells. In this study, 72 single nucleotide polymorphisms (SNPs) associated with 43 SS gene risk factors were selected from publicly available and peer reviewed literature for further in silico analysis. SS risk variant location was tested revealing a broad distribution in coding sequences (5.6%), intronic sequences (55.6%), upstream/downstream genic regions (30.5%), and intergenic regions (8.3%). Moreover, a significant enrichment of regulatory motifs (promoter, enhancer, insulator, DNAse peak, and expression quantitative trait loci) characterizes SS risk variants (94.4%). Next, screening SNPs in high linkage disequilibrium (r 2 ≥ 0.8 in Caucasians) revealed 645 new variants including 5 SNPs with missense mutations, and indicated an enrichment of transcriptionally active motifs according to the cell type (B cells > monocytes > T cells ≫ A549). Finally, we looked at SS risk variants for histone markers in B cells (GM12878), monocytes (CD14 + ) and epithelial cells (A548). Active histone markers were associated with SS risk variants at both promoters and enhancers in B cells, and within enhancers in monocytes. In conclusion and based on the obtained in silico results that need further confirmation, associations were observed between SS genetic risk factors and epigenetic factors and these associations predominate in B cells, such as those observed at the FAM167A-BLK locus.
Rheumatology, 2014
The aim of this study was to evaluate whether salivary gland ultrasonography (SGUS) improves the ... more The aim of this study was to evaluate whether salivary gland ultrasonography (SGUS) improves the diagnostic performance of the 2012 ACR classification criteria for SS. We studied a cohort of 101 patients with suspected SS seen at a single centre in Brittany, France. An SGUS echostructure score ≥2 was considered abnormal. The reference standard was a clinical diagnosis of SS made by a group of experts blinded to SGUS findings. SS was diagnosed in 45 patients. Similar proportions of patients with and without SS had an ocular staining score ≥3. Adding RF positivity and ANA titre ≥1:320 as an alternative to anti-SSA/SSB positivity increased the sensitivity of the serological item without modifying specificity compared with using anti-SSA/SSB alone. SGUS was 60.0% sensitive and 87.5% specific for SS. Adding the SGUS score to the ACR criteria increased sensitivity from 64.4% to 84.4% and only slightly decreased specificity, from 91.1% to 89.3%. The diagnostic performance of the ACR classification criteria for SS is notably improved by adding the SGUS score. SGUS should be included in future classification criteria for SS.
Arthritis Research & Therapy, 2014
The aims of this study were to evaluate the diagnostic accuracy of blood B-cell subset profiling ... more The aims of this study were to evaluate the diagnostic accuracy of blood B-cell subset profiling and immune-system activation marker assays in primary Sjögren's syndrome (pSS) and to assess whether adding these tools to the current laboratory item would improve the American-European Consensus Group (AECG) criteria.
Arthritis & Rheumatism, 2007
Objective. There is evidence to support a dominant role for B cells in the pathophysiology of pri... more Objective. There is evidence to support a dominant role for B cells in the pathophysiology of primary Sjö gren's syndrome (SS). Therefore, we evaluated the safety and efficacy of anti-CD20 monoclonal antibody.
Joint Bone Spine, 2009
Rituximab is a monoclonal antibody to CD20, an antigen found on B cells. It was developed for the... more Rituximab is a monoclonal antibody to CD20, an antigen found on B cells. It was developed for the treatment of B cell lymphomas but was subsequently found useful in a number of autoimmune disorders. The efficacy of rituximab varies with the maturity and location of the target B cells, nature of the effector cells, pharmacokinetic considerations, time to B cell depletion and time to B cell restoration. As a result, substantial variability occurs across patients and between courses in a given patient. Laboratory tests can be used to monitor the effects of rituximab. Tests that predict the treatment response include CD20 density, Fc gamma IIIa receptor genotype and complement efficiency. To monitor the effect of rituximab, pharmacokinetic tests, B cell counts and xenoantibody levels are useful. Finally, to determine whether retreatment is in order, specific B cell subsets or autoantibodies can be looked for. None of the available tests is entirely reliable.
Autoimmunity Reviews, 2010
Annals of the Rheumatic Diseases, 2014
ABSTRACT The immunosuppressive function of regulatory B cells (Breg) is defective in B cells from... more ABSTRACT The immunosuppressive function of regulatory B cells (Breg) is defective in B cells from systemic lupus erythematosus (SLE) patients. Since the Ca(2+) pathway is also altered in SLE B cells, the aim of the study was to explore the contribution of the Ca(2+) channel Orai1 and its regulator, the stromal interaction molecule 1 (STIM1), on regulatory B cell functions. Thirty SLE patients and healthy controls (HC) were included in the study. Orai1 and STIM1 expressions were explored in CD40/CpG activated B cells, and in the stimulated (anti-CD3, anti-CD28 plus CpG-ODN 2006) T- and B- cell autologous co-culture Breg model. Transfection were used using either siRNAs to down-modulate STIM1 in SLE B cells, or either the cDNA STIM1 vector in HC B cells. After 3 days, in CD40/CpG activated HC B cells, and in HC B cells stimulated during co-cultures, acquisition of the Breg phenotype (IgD/CD38/CD24/CD5(high)) was associated with an over-expression of the Ca(2+) regulator STIM1 (x10.8 and x7.1 fold increase respectively). At day 4 and even more at day 5, STIM1 expression declined in co-cultures and this down-regulation was accompanied with IL-10 and TGF-beta up-regulation in B cells, FoxP3(+) regulatory T cell expansion, and a reduction of T cell proliferation. Expression of the Ca(2+) channel Orai1 was stable. In SLE B cells, STIM1 expression was overexpressed at basal level when compared to HC B cells (x4.3 fold) and remains elevated in B cells during all the time of the autologous co-culture (x8.8 fold). Then we hypothesised that maintaining high levels of STIM1 was critic in the regulatory capacity of SLE B cells. Accordingly, we demonstrated that STIM1 downregulation in SLE B cells, using a specific siRNA, was effective to restore IL-10, but not TGF-beta, expression, FoxP3(+) regulatory SLE T cell expansion, and SLE T cell inhibition. In HC B cells, forcing STIM1 expression, with a STIM1 vector, was effective to reproduce the abnormalities observed in SLE B cells. No association was observed between STIM1 expression at basal level and organ involvement, disease activity (SLEDAI), or serological parameters thus suggesting that STIM1 over-expression and Ca(2+) dysregulations are primary events in SLE. Altogether, this study reveals that acquisition of the Breg phenotype and Breg functions are tightly regulated by STIM1. Furthermore, this observation could provide innovative B-cell based treatment to convert B cells into immunosuppressive cells with applications in human autoimmunity and in SLE. lupus, regulatory B cells, calcium, STIM1, IL-10.
Blood, 2010
globulin (IVIg) may operate through the insertion of its Fc part into the Fc-␥ receptor, or the b... more globulin (IVIg) may operate through the insertion of its Fc part into the Fc-␥ receptor, or the binding of its sialic acid (SA)bearing glycans to the negatively regulating CD22 lectin. It appeared that IVIg reduces B lymphocyte viability in a dose-and time-dependent manner. Furthermore, we show by confocal microscopy that SApositive IgG, but not SA-negative IgG bind to CD22. This interaction reduces the strength of B-cell receptor-mediated signaling trough down-regulating tyrosine phosphorylation of Lyn and the B-cell linker proteins, and up-regulating phospholipase C␥2 activation. This cascade resulted in a sustained activation of Erk 1/2 and arrest of the cell cycle at the G 1 phase. These changes may be accounted for the efficacy of IVIg in autoimmune diseases. (Blood. 2010;116(10): 1698-1704)
European Journal of Clinical Investigation, 2013
Background Lupus is a prototype autoimmune disease of unknown aetiology. The disease is complex; ... more Background Lupus is a prototype autoimmune disease of unknown aetiology. The disease is complex; manifest diverse clinical symptoms and disease mechanisms. This complexity has provided many leads to explore: from disease mechanisms to approaches for therapy. B-lymphocytes play a central role in the pathogenesis of the disease. However, the cause of aberrant B-lymphocyte responses in patients and, indeed, its causal relationship with the disease remain unclear.
International Reviews of Immunology, 2013
Lupus is a complex autoimmune rheumatic disease of unknown aetiology. The disease is associated w... more Lupus is a complex autoimmune rheumatic disease of unknown aetiology. The disease is associated with diverse features of immunological abnormality in which B-lymphocytes play a central role. However, the cause of atypical B-lymphocyte responses remains unclear. In this article, we provide a synopsis of current knowledge on intracellular signalling abnormalities in B-lymphocytes in lupus and their potential effects on the response of these cells in mouse models and in patients. There are numerous reported defects in the regulation of intracellular signalling proteins and pathways in B-lymphocytes in lupus that, potentially, affect critical biological responses. Most of the evidence for these defects comes from studies of disease models and genetically engineered mice. However, there is also increasing evidence from studying B-lymphocytes from patients and from genome-wide linkage analyses for parallel defects to those observed in mice. These studies provide molecular and genetic explanations for the key immunological abnormalities associated with lupus. Most of the new information appears to relate to defects in intracellular signalling that impact B-lymphocyte tolerance, cytokine production and responses to infections. Some of these abnormalities will be discussed within the context of disease pathogenesis.
Journal of Autoimmunity, 2012
The prominent feature of immunological defects in systemic lupus erythematosus (SLE) is the produ... more The prominent feature of immunological defects in systemic lupus erythematosus (SLE) is the production of autoantibodies (auto-Abs) to nuclear antigens including DNA, histones and RNP. In addition, there is growing evidence that epigenetic changes play a key role in the pathogenesis of SLE. Autoreactive CD4 þ T cells and B cells in patients with SLE have evidence of altered patterns of DNA methylation as well as post-translational modifications of histones and ribonucleoproteins (RNP). A key question that has emerged from these two characteristic features of SLE is whether the two processes are linked. New data provide support for such a link. For example, there is evidence that hypomethylated DNA is immunogenic, that anti-histone auto-Abs in patients with SLE bind epigenetic-sensitive hot spots and that epigenetically-modified RNP-derived peptides can modulate lupus disease. All in all, the available evidence indicates that a better understanding of dysregulation in epigenetics in SLE may offer opportunities to develop new biomarkers and novel therapeutic strategies.
The Journal of Immunology, 2009
B lymphocytes from patients with systemic lupus erythematosus (SLE) are characterized by reduced ... more B lymphocytes from patients with systemic lupus erythematosus (SLE) are characterized by reduced expression levels of membrane CD5. Recent studies from our laboratory have revealed that the level of membrane CD5 is determined by the relative level of two alternative CD5 isoforms; CD5-E1A, which is expressed on the membrane, and CD5-E1B, which is retained in the cytoplasm. Using bisulfite sequencing and methylation-sensitive endonuclease assays we show that the promoter for the alternative CD5-E1B isoform is demethylated in B cells from patients with SLE but not in healthy controls. We go on to show that differential methylation is more pronounced following BCR engagement. As a result of this demethylation, CD5-E1B mRNA is transcribed at the expense of CD5-E1A mRNA transcription. We provide further evidence that production of high IL-6
Arthritis & Rheumatism, 2007
Treatment with rituximab depletes B cells from the peripheral blood (PB) and salivary glands (SGs... more Treatment with rituximab depletes B cells from the peripheral blood (PB) and salivary glands (SGs) of patients with primary Sjögren's syndrome (SS). The purpose of this study was to track the repopulation of B cell subsets in PB as well as their subsequent homing into SGs in patients with primary SS treated with rituximab. A series of 4-color flow cytometry experiments delineated B cell subsets in 15 patients with primary SS. All were tested on days 8 and 15 of treatment. Nine of the patients were followed up monthly for 10 months, and the remaining 6 patients were followed up monthly for 24 months. Enzyme-linked immunosorbent assays were developed to measure serum levels of BAFF and rituximab. SGs were biopsied at the start of the study and 4 months after treatment in 15 patients, 12 months after treatment in 3 patients, and 24 months after treatment in 2 patients. Baseline serum levels of BAFF correlated inversely (r = -0.92, P < 5 x 10(-4)) with the duration of B cell depletion: the higher the BAFF levels, the shorter the duration of B cell depletion. Four B cell subsets repopulated the PB: plasmablasts (CD19+, CD5-,IgD-,CD38++), transitional type 1 (T1) B cells (CD19+,CD5+,IgD+,CD38++), mature Bm2 cells (CD19+,CD5+/-,IgD+,CD38+/-), and memory B cells (CD19+,CD5-,IgD-,CD38-). Increased numbers of Bm2 cells and decreased memory B cells reappeared with time. Sequential SG biopsies revealed that B cells were absent in these glands for 12 months: they were detected 24 months after rituximab treatment. Memory and T1 B cells were the first B cells identified locally. The timing of B cell repopulation is modulated by BAFF and is followed by reconstitution of the preexisting abnormalities.
Immuno Anal Biol Spec, 2011
Glomerulonephritis is the most serious complication of systemic lupus erythematosus (SLE). Indeed... more Glomerulonephritis is the most serious complication of systemic lupus erythematosus (SLE). Indeed, lupus nephritis evolves by flares that must be addressed as soon as possible, or better be prevented. As a consequence, the immunological diagnosis of this autoimmune disease is essential in conjunction with the monitoring of the renal function. Although hundreds of antibodies have been identified in SLE, some of them seem to accompany or announce the renal disease: anti-dsDNA, anti-nucleosome, anti-α-actinin, and anti-C1q antibodies. This issue aims to communicate the reasons for the tropism of such autoantibodies to the kidneys, and present the interest of these autoantibodies for the diagnosis and the monitoring of lupus nephritis.La glomérulonéphrite est la complication la plus grave du lupus érythémateux disséminé. Cette néphrite lupique peut évoluer par poussées qu’il faut traiter le plus tôt possible, voire prévenir. Son diagnostic est donc essentiel, ainsi que la surveillance du rein. Il s’agit d’une maladie auto-immune où plus d’une centaine d’auto-anticorps (Ac) ont été répertoriés ! Mais, certains d’entre eux, tels que les Ac anti-ADNnatif, les Ac antinucléosomes, les Ac anti-α-actinine et les Ac anti-C1q, semblent accompagner ou annoncer une atteinte rénale. Cette mise au point vise à communiquer les raisons du tropisme de ces auto-Ac pour les reins et, partant, d’en mesurer l’intérêt de chacun d’entre eux pour le diagnostic et la veille au long cours de la néphropathie lupique.
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Papers by Yves Renaudineau