66 research outputs found
Changes Related to Age in Natural and Acquired Systemic Self-IgG Responses in Malaria
Background. Absence of acquired protective immunity in endemic areas children leads to higher susceptibility to severe malaria. To investigate the involvement of regulatory process related to self-reactivity, we evaluated potent changes in auto-antibody reactivity profiles in children and older subjects living in malaria-endemic zones comparatively to none-exposed healthy controls. Methods. Analysis of IgG self-reactive footprints was performed using Western blotting against healthy brain antigens. Plasmas of 102 malaria exposed individuals (MEIs) from endemic zone, with or without cerebral malaria (CM) were compared to plasmas from non-endemic controls (NECs). Using linear discriminant and principal component analysis, immune footprints were compared by counting the number, the presence or absence of reactive bands. We identified the most discriminant bands with respect to age and clinical status. Results. A higher number of bands were recognized by IgG auto-antibodies in MEI than in NEC. Characteristic changes in systemic self-IgG-reactive repertoire were found with antigenic bands that discriminate Plasmodium falciparum infections with or without CM according to age. 8 antigenic bands distributed in MEI compared with NEC were identified while 6 other antigenic bands were distributed within MEI according to the age and clinical status. Such distortion might be due to evolutionary processes leading to pathogenic/protective events
Classical pathway activity C3c, C4 and C1-inhibitor protein reference intervals determination in EDTA plasma
Introduction: Reference intervals (RIs) for complement assays in EDTA plasma samples have not previously been published. The objectives of the
present study were to validate and/or determine RIs for classical pathway (CP50) activity and C3c, C4 and C1 inhibitor protein (C1INH) assays and to
assess the need for age-specific RIs in EDTA plasma.
Materials and methods: We retrospectively evaluated a cohort of 387 patients attending our university hospital and known to be free of complement-
modifying diseases. The need for age partitioning was assessed and RIs were calculated according to the CLSI protocol.
Results: No need for age partitioning was evidenced for CP50 activity, C3c and C4 concentrations and RIs (90% CI) were calculated from the pooled
data: 35.4 (33.1-37.2) to 76.3 (73.7-83.6) U/mL for CP50 activity, 0.80 (0.75-0.87) to 1.64 (1.59-1.72) g/L for C3c, and 0.12 (0.10-0.14) to 0.38 (0.36-
0.40) g/L for C4. Our results highlight a positive association between age and C1INH concentrations. We derived 3 age partitions (6 months to 30
years, 30-50 and > 50 years) and the related RIs: 0.20 (0.18-0.21) to 0.38 (0.36-0.40) g/L, 0.22 (0.20-0.24) to 0.39 (0.36-0.41) g/L and 0.25 (0.22-0.27)
to 0.41 (0.40-0.43) g/L, respectively).
Conclusions: The newly determined RIs for CP50 activity were higher than those provided by the manufacturer for EDTA plasma samples, whereas
those for C3c and C4 RIs were similar to the values provided for serum samples. The C1INH concentration and activity were found to be associated
with age and age-specific RIs are mandatory for this analyte
Prevalence and Clinical Associations of Antiphospholipid Antibodies in Systemic Sclerosis: New Data From a French Cross-Sectional Study, Systematic Review, and Meta-Analysis
Objectives: Antiphospholipid antibodies (aPL) can be present in the sera of systemic sclerosis (SSc) patients. This study aimed to determine the prevalence of aPL in a cross-sectional study of SSc patients, to assess their clinical associations, to perform a systematic review of published reports and a meta-analysis to estimate the worldwide prevalence of aPL in SSc.Methods: Two-hundred and forty-nine SSc patients were consecutively tested once for lupus anticoagulant (LA), anticardiolipin (aCL), and anti-ÎČ2glycoprotein I (anti-ÎČ2GpI) antibodies. Clinical associations with aPL positivity were studied using a logistic regression model. A systematic review of the literature was carried out in PubMed and Embase. Meta-analysis was performed using number of aPL positive (at least one of the three antibodies positive) and negative patients. Meta-regression was used to study potential factors explaining the heterogeneity between studies.Results: In our cross-sectional study, aPL positivity was found in 16 patients (prevalence 6.4%; 95%CI [3.8â10.4]). In multivariate analysis, there was a significant association between aPL positivity and venous thrombosis (VT) (OR 6.25 [1.18â33.00]; p = 0.028) and miscarriage (OR 5.43; 95%CI [1.31â22.13]; p = 0.017). Twenty-four studies were included in the meta-analysis, representing a total population of 3036 SSc patients. The overall pooled prevalence of aPL in SSc was 14% (9â20) with a high degree of heterogeneity among studies.Conclusion: This study found a prevalence of aPL positivity in our SSc population of 6.4% (3.8â10.4) and an overall worldwide pooled prevalence of 14% (9â20). In our SSc population, aPL positivity was associated with VT and miscarriage. These data provide additional insights into the role of aPL in the vasculopathy observed in SSc
Soluble markers of B cell activation suggest a role of B cells in the pathogenesis of systemic sclerosis-associated pulmonary arterial hypertension
IntroductionSoluble markers of B cell activation are interesting diagnostic and prognostic tools in autoimmune diseases. Data in systemic sclerosis (SSc) are scarce and few studies focused on their association with disease characteristics.Methods1. Serum levels of 14 B cell biomarkers (ÎČ2-microglobulin, rheumatoid factor (RF), immunoglobulins (Ig) G, IgA, IgM, BAFF, APRIL, soluble (s)TACI, sBCMA sCD21, sCD23, sCD25, sCD27, CXCL13) were measured in SSc patients and healthy controls (HC). 2. Associations between these biomarkers and SSc characteristics were assessed. 3. The pathophysiological relevance of identified associations was explored by studying protein production in B cell culture supernatant.ResultsIn a discovery panel of 80 SSc patients encompassing the broad spectrum of disease manifestations, we observed a higher frequency of RF positivity, and increased levels of ÎČ2-microglobulin, IgG and CXCL13 compared with HC. We found significant associations between several biomarkers and SSc characteristics related to disease phenotype, activity and severity. Especially, serum IgG levels were associated with pulmonary hypertension (PH); ÎČ2-microglobulin with Nt-pro-BNP and DLCO; and BAFF with peak tricuspid regurgitation velocity (TRV). In a validation cohort of limited cutaneous SSc patients without extensive ILD, we observed lower serum IgG levels, and higher ÎČ2-microglobulin, sBCMA, sCD23 and sCD27 levels in patients with pulmonary arterial hypertension (PAH). BAFF levels strongly correlated with Nt-pro-BNP levels, FVC/DLCO ratio and peak TRV in SSc-PAH patients. Cultured SSc B cells showed increased production of various angiogenic factors (angiogenin, angiopoietin-1, VEGFR-1, PDGF-AA, MMP-8, TIMP-1, L-selectin) and decreased production of angiopoietin-2 compared to HC.ConclusionSoluble markers of B cell activation could be relevant tools to assess organ involvements, activity and severity in SSc. Their associations with PAH could plead for a role of B cell activation in the pathogenesis of pulmonary microangiopathy. B cells may contribute to SSc vasculopathy through production of angiogenic mediators
CD3 -CD4 + lymphoid variant of hypereosinophilic syndrome: nodal and extranodal histopathological and immunophenotypic features of a peripheral indolent clonal T-cell lymphoproliferative disorder
Serological Proteomic Approach (SERPA) : a using tool for identifying discriminant reactivities in autoimmune diseases?
Dans le cadre du diagnostic biologique des maladies auto-immunes, les autoanticorpssont gĂ©nĂ©ralement recherchĂ©s par des mĂ©thodes qui utilisent des antigĂšnes(ou peptides) prĂ©sĂ©lectionnĂ©s. De telles techniques ont des limites qui pourraient ĂȘtrecontournĂ©es par de nouvelles approches. Dans le premier temps de ce travail, nousrapportons l'intĂ©rĂȘt dâĂ©valuer les rĂ©activitĂ©s d'auto-anticorps vis-Ă -vis de ciblesmodifiĂ©es par des processus post traductionnels, comme la citrullination dans lecadre diagnostique de la polyarthrite rhumatoĂŻde. Cette approche ne peut toutefoispas ĂȘtre transposĂ©e Ă toutes les pathologies auto-immunes, et notamment lasclĂ©rose en plaques. Dans un deuxiĂšme temps, notre dĂ©marche sâest Ă©largie Ă lâanalyse globale de la rĂ©activitĂ© des immunoglobulines G sĂ©riques dirigĂ©e contrediffĂ©rents extraits dâantigĂšnes tissulaires, notamment issus du cerveau. MalgrĂ© lagrande hĂ©tĂ©rogĂ©nĂ©itĂ© des rĂ©ponses interindividuelles, il a Ă©tĂ© possible dâobserver desprofils de rĂ©activitĂ©s distinguant les sujets sains de patients souffrant de diffĂ©rentespathologies Ă composantes auto-immunes. Cette signature sĂ©rologique permetĂ©galement de distinguer les profils auto-immuns associĂ©s Ă diffĂ©rentes maladies etmĂȘme de distinguer leurs formes cliniques. Dans le modĂšle expĂ©rimental dĂ©veloppĂ©au laboratoire, nous avons observĂ© que des modifications de ces profils apparaissentde façon prĂ©coce et peuvent ĂȘtre liĂ©s Ă une Ă©volution pĂ©jorative ou favorable de lamaladie auto-immune. Ces rĂ©sultats ont Ă©tĂ© confirmĂ©s dans la sclĂ©rose en plaques,oĂč lâĂ©tude menĂ©e chez des patients ne prĂ©sentant quâun syndrome clinique isolĂ©, amontrĂ© que les profils de rĂ©activitĂ© sĂ©rique des IgG sont dĂ©jĂ marquĂ©s de lâempreintede la maladie qui se rĂ©vĂšlera cliniquement en moyenne trois ans plus tard. De façonintĂ©ressante, d'autres travaux ont montrĂ© que le rĂ©pertoire des IgM pouvaitĂ©galement ĂȘtre perturbĂ© au cours dâun processus auto-immun dont la pathogĂ©nierepose sur un dysfonctionnement des lymphocytes T (syndrome APECED). CesrĂ©sultats suggĂšrent que des mĂ©canismes T dĂ©pendants mais aussi T indĂ©pendantspĂšsent sur la constitution et lâentretien du rĂ©pertoire auto-immun pathologique.Pour identifier les cibles des rĂ©activitĂ©s discriminantes rĂ©vĂ©lĂ©es par cette premiĂšreapproche, nous avons dĂ©veloppĂ© une technique de caractĂ©risation molĂ©culairefaisant appel Ă la technique immunoprotĂ©omique. Alors que les pathologieshumaines et les modĂšles animaux Ă©tudiĂ©s sont principalement des pathologiesspĂ©cifiques dâorgane, les antigĂšnes tissulaires qui ont Ă©tĂ© identifiĂ©s comme cibles desrĂ©activitĂ©s spĂ©cifiquement associĂ©es Ă ces pathologies sont des antigĂšnesubiquitaires, et non des antigĂšnes spĂ©cifiques dâorgane. Ces rĂ©sultats posent laquestion de lâimplication rĂ©elle de ces cibles dans la physiopathologie des maladiesauto-immunes. Ils illustrent Ă©galement lâimpĂ©rative nĂ©cessitĂ© de connaĂźtre les limitesdes rĂ©sultats apportĂ©s par les mĂ©thodes dâimmunoprotĂ©omique.La caractĂ©risation de la signature sĂ©rologique dâun processus pathologique, autravers de lâanalyse des perturbations globales des rĂ©activitĂ©s sĂ©riques qui lui sontassociĂ©es, offre des perspectives intĂ©ressantes tant en termes de prise en charge dupatient quâen termes de comprĂ©hension physiopathologique des maladies autoimmunes.Elle pourrait aboutir Ă dâutiles dĂ©bouchĂ©s thĂ©rapeutiques. Ces attentesjustifient pleinement lâinvestissement qui a Ă©tĂ© mis en place par notre laboratoiredans le cadre de sa validation mĂ©thodologique.In autoimmune diseases, specific autoantibodies detected in patientsâ sera areusually investigated by techniques using purified self-antigens and/or relevantpeptides from preselected targets. Such a restrictive view may be overcome by usingnew biological techniques to improve the diagnostic procedure. In a first step, weevaluated the impact of slight changes in target self-antigens related to posttranslationalmodifications, such as citrullination. In view of the weak resultsobtained, we further focused on some properties of the humoral response. Westudied the global self-reactive IgG antibody patterns against a large panel ofantigens derived from different target tissue extracts, especially brain antigens.Despite inter-individual differences, some reactivities allowed us to discriminatebetween the immune profiles of healthy individuals and those of patients. The selfreactivefootprints can also differentiate distinct autoimmune diseases and theirclinical forms. When we induced experimental autoimmune diseases, dynamicchanges occurred at the early phases with significant patterns related to pathogenicor protective events. A pathological distortion of the self-reactive antibodyrepertoire was also found in clinically isolated syndromes predictive of multiplesclerosis. Despite the predominant organ-specific symptoms in the clinical andexperimental situations studied, discriminant self-IgG reactivities mostly involvedubiquitous antigens rather than organ specific targets. Interestingly, discriminantIgM reactivities targeting both tissue-specific and ubiquitous antigens were alsospecifically observed in a T-dependent autoimmune disease (autoimmunepolyendocrinopathy syndrome), suggesting that T-cell-dependent but also T-cellindependentmechanisms might be involved in pathological changes in the selfreactiverepertoire. Although these footprints have allowed the identification ofuseful new biomarkers, their pathophysiological relevance remains to be defined.The molecular characterization of specific antigenic targets in autoimmune disease isa critical step towards understanding the pathological mechanisms and developinguseful diagnostic and therapeutic tools. In this perspective, we emphasize the needfor accurate methodological approaches. Our analysis of self-reactive footprintshighlights the potent role of complementary events related to putative dysfunctionin the innate/natural immune response in autoimmune diseases
Approche immunoprotéomique : valeurs et limites pour l'identification de réactivités discriminantes d'anticorps auto-immuns
In autoimmune diseases, specific autoantibodies detected in patientsâ sera areusually investigated by techniques using purified self-antigens and/or relevantpeptides from preselected targets. Such a restrictive view may be overcome by usingnew biological techniques to improve the diagnostic procedure. In a first step, weevaluated the impact of slight changes in target self-antigens related to posttranslationalmodifications, such as citrullination. In view of the weak resultsobtained, we further focused on some properties of the humoral response. Westudied the global self-reactive IgG antibody patterns against a large panel ofantigens derived from different target tissue extracts, especially brain antigens.Despite inter-individual differences, some reactivities allowed us to discriminatebetween the immune profiles of healthy individuals and those of patients. The selfreactivefootprints can also differentiate distinct autoimmune diseases and theirclinical forms. When we induced experimental autoimmune diseases, dynamicchanges occurred at the early phases with significant patterns related to pathogenicor protective events. A pathological distortion of the self-reactive antibodyrepertoire was also found in clinically isolated syndromes predictive of multiplesclerosis. Despite the predominant organ-specific symptoms in the clinical andexperimental situations studied, discriminant self-IgG reactivities mostly involvedubiquitous antigens rather than organ specific targets. Interestingly, discriminantIgM reactivities targeting both tissue-specific and ubiquitous antigens were alsospecifically observed in a T-dependent autoimmune disease (autoimmunepolyendocrinopathy syndrome), suggesting that T-cell-dependent but also T-cellindependentmechanisms might be involved in pathological changes in the selfreactiverepertoire. Although these footprints have allowed the identification ofuseful new biomarkers, their pathophysiological relevance remains to be defined.The molecular characterization of specific antigenic targets in autoimmune disease isa critical step towards understanding the pathological mechanisms and developinguseful diagnostic and therapeutic tools. In this perspective, we emphasize the needfor accurate methodological approaches. Our analysis of self-reactive footprintshighlights the potent role of complementary events related to putative dysfunctionin the innate/natural immune response in autoimmune diseases.Dans le cadre du diagnostic biologique des maladies auto-immunes, les autoanticorpssont gĂ©nĂ©ralement recherchĂ©s par des mĂ©thodes qui utilisent des antigĂšnes(ou peptides) prĂ©sĂ©lectionnĂ©s. De telles techniques ont des limites qui pourraient ĂȘtrecontournĂ©es par de nouvelles approches. Dans le premier temps de ce travail, nousrapportons l'intĂ©rĂȘt dâĂ©valuer les rĂ©activitĂ©s d'auto-anticorps vis-Ă -vis de ciblesmodifiĂ©es par des processus post traductionnels, comme la citrullination dans lecadre diagnostique de la polyarthrite rhumatoĂŻde. Cette approche ne peut toutefoispas ĂȘtre transposĂ©e Ă toutes les pathologies auto-immunes, et notamment lasclĂ©rose en plaques. Dans un deuxiĂšme temps, notre dĂ©marche sâest Ă©largie Ă lâanalyse globale de la rĂ©activitĂ© des immunoglobulines G sĂ©riques dirigĂ©e contrediffĂ©rents extraits dâantigĂšnes tissulaires, notamment issus du cerveau. MalgrĂ© lagrande hĂ©tĂ©rogĂ©nĂ©itĂ© des rĂ©ponses interindividuelles, il a Ă©tĂ© possible dâobserver desprofils de rĂ©activitĂ©s distinguant les sujets sains de patients souffrant de diffĂ©rentespathologies Ă composantes auto-immunes. Cette signature sĂ©rologique permetĂ©galement de distinguer les profils auto-immuns associĂ©s Ă diffĂ©rentes maladies etmĂȘme de distinguer leurs formes cliniques. Dans le modĂšle expĂ©rimental dĂ©veloppĂ©au laboratoire, nous avons observĂ© que des modifications de ces profils apparaissentde façon prĂ©coce et peuvent ĂȘtre liĂ©s Ă une Ă©volution pĂ©jorative ou favorable de lamaladie auto-immune. Ces rĂ©sultats ont Ă©tĂ© confirmĂ©s dans la sclĂ©rose en plaques,oĂč lâĂ©tude menĂ©e chez des patients ne prĂ©sentant quâun syndrome clinique isolĂ©, amontrĂ© que les profils de rĂ©activitĂ© sĂ©rique des IgG sont dĂ©jĂ marquĂ©s de lâempreintede la maladie qui se rĂ©vĂšlera cliniquement en moyenne trois ans plus tard. De façonintĂ©ressante, d'autres travaux ont montrĂ© que le rĂ©pertoire des IgM pouvaitĂ©galement ĂȘtre perturbĂ© au cours dâun processus auto-immun dont la pathogĂ©nierepose sur un dysfonctionnement des lymphocytes T (syndrome APECED). CesrĂ©sultats suggĂšrent que des mĂ©canismes T dĂ©pendants mais aussi T indĂ©pendantspĂšsent sur la constitution et lâentretien du rĂ©pertoire auto-immun pathologique.Pour identifier les cibles des rĂ©activitĂ©s discriminantes rĂ©vĂ©lĂ©es par cette premiĂšreapproche, nous avons dĂ©veloppĂ© une technique de caractĂ©risation molĂ©culairefaisant appel Ă la technique immunoprotĂ©omique. Alors que les pathologieshumaines et les modĂšles animaux Ă©tudiĂ©s sont principalement des pathologiesspĂ©cifiques dâorgane, les antigĂšnes tissulaires qui ont Ă©tĂ© identifiĂ©s comme cibles desrĂ©activitĂ©s spĂ©cifiquement associĂ©es Ă ces pathologies sont des antigĂšnesubiquitaires, et non des antigĂšnes spĂ©cifiques dâorgane. Ces rĂ©sultats posent laquestion de lâimplication rĂ©elle de ces cibles dans la physiopathologie des maladiesauto-immunes. Ils illustrent Ă©galement lâimpĂ©rative nĂ©cessitĂ© de connaĂźtre les limitesdes rĂ©sultats apportĂ©s par les mĂ©thodes dâimmunoprotĂ©omique.La caractĂ©risation de la signature sĂ©rologique dâun processus pathologique, autravers de lâanalyse des perturbations globales des rĂ©activitĂ©s sĂ©riques qui lui sontassociĂ©es, offre des perspectives intĂ©ressantes tant en termes de prise en charge dupatient quâen termes de comprĂ©hension physiopathologique des maladies autoimmunes.Elle pourrait aboutir Ă dâutiles dĂ©bouchĂ©s thĂ©rapeutiques. Ces attentesjustifient pleinement lâinvestissement qui a Ă©tĂ© mis en place par notre laboratoiredans le cadre de sa validation mĂ©thodologique
Immuno-empreinte (outil d'identification des anticorps anti-SS-A/RO 52 KDA associés aux processus pathologiques)
LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF
Détection des anticorps anti-ADN natif pour le diagnostic du lupus erythémateux systématique (étude comparative de 7 trousses de dosage immuno-enzymatique et d'un test de Farr)
LILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF
Dosage des anticorps antiphosphatidylĂ©thanolamine (dĂ©veloppement mĂ©thodologique et intĂ©rĂȘt dans la prise en charge diagnostique des diffĂ©rentes formes cliniques du syndrome des antiphospholipides)
LILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF
- âŠ