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V Frémeaux-Bacchi

Publications and source records attributed to V Frémeaux-Bacchi.

At least 19 recordsLinked to original sources
PubMed2006

[Complement factor I deficiency revealed by repeated systemic Streptococcus pneumoniae infection].

Recurrent and serious otitis media, and 2 Streptococcus pneumoniae bacteraemia episodes evoked an immune system deficiency in a 6-year-old girl. Upon investigation of the complement system, CH50 activity was moderately reduced and C4 antigen level was normal contrasting with low C3 antigen level. Factor 1 was undetectable. Factor I deficiency is rare, and its diagnosis has important practical consequences. Thanks to preventive antibiotic therapy with penicillin V and vaccinations against Neisseria meningitidis and S. pneumoniae, life expectancy and quality of this child can be significantly improved.

Anti-Bacterial Agents↗
PubMed2006

Phenotypic expression of factor H mutations in patients with atypical hemolytic uremic syndrome.

We investigated the phenotypic expression of factor H mutations in two patients with atypical hemolytic uremic syndrome (HUS). Factor H in serum was assayed by rocket immunoelectrophoresis, immunoblotting, and double immunodiffusion and in tissue by immunohistochemistry. Functional activity was analyzed by hemolysis of sheep erythrocytes and binding to endothelial cells. A homozygous mutation in complement control protein (CCP) domain 10 of factor H was identified in an adult man who first developed membranoproliferative glomerulonephritis and later HUS. C3 levels were very low. The patient had undetectable factor H levels in serum and a weak factor H 150 kDa band. Double immunodiffusion showed partial antigenic identity with factor H in normal serum owing to the presence of factor H-like protein 1. Strong specific labeling for factor H was detected in glomerular endothelium, mesangium and in glomerular and tubular epithelium as well as in bone marrow cells. A heterozygous mutation in CCP 20 of factor H was found in a girl with HUS. C3 levels were moderately decreased at onset. Factor H levels were normal and a normal 150 kDa band was present. Double immunodiffusion showed antigenic identity with normal factor H. Factor H labeling was minimal in the renal cortex. Factor H dysfunction was demonstrated by increased sheep erythrocyte hemolysis and decreased binding to endothelial cells. In summary, two different factor H mutations associated with HUS were examined: in one, factor H accumulated in cells, and in the other, membrane binding was reduced.

Animals↗
PubMed2004

[Acquired C1 inhibitor deficiency associated with lymphoproliferative disorders: four cases].

INTRODUCTION: Acquired C1 inhibitor deficiency is sometimes associated with lymphoproliferative disorders. EXEGESIS: We report four cases of acquired C1 inhibitor deficiency in association with lymphoproliferative disorders. Three of them were asymptomatic; one was associated with abdominal pain. Four women (median age, 66 years) presented either two non-Hodgkin lymphoma or two chronic lymphocytic leukaemia. C1 inhibitor deficiency was detected fortuitous (n = 1) or during investigation of arthralgia (n = 2), or Gougerot-Sjogren syndrome (n = 1). The deficit was acquired in all cases type I. Auto-immune disorders were associated with: Gougerot-Sjogren syndrome (n = 1), cryoglobulinemia (n = 2), IgM lambda monoclonal gammopathy (n = 1), Coombs positive test (n = 2), IgG anti-cardiolipine antibodies (n = 1). C1 inhibitor deficiency was not modified after lymphoproliferative disorders treatment (radiotherapy, splenic ablation) in two cases but patients were not in complete remission. C1 inhibitor raised normal level in one case, after five chemotherapy regimens, but decreased complement level and C4 split persist. CONCLUSION: Acquired C1 inhibitor deficiency associated with lymphoproliferative disorders is sometimes asymptomatic. Diagnosis could be delay in spite of clinical manifestations. Deficit correction is not constant after lymphoproliferative disorders treatment.

Aged↗
PubMed2001

Molecular basis of a selective C1s deficiency associated with early onset multiple autoimmune diseases.

We have investigated the molecular basis of selective and complete C1s deficiency in 2-year-old girl with complex autoimmune diseases including lupus-like syndrome, Hashimoto's thyroiditis, and autoimmune hepatitis. This patient's complement profile was characterized by the absence of CH50 activity, C1 functional activity <10%, and undetectable levels of C1s Ag associated with normal levels of C1r and C1q Ags. Exon-specific amplification of genomic DNA by PCR followed by direct sequence analysis revealed a homozygous nonsense mutation in the C1s gene exon XII at codon 534, caused by a nucleotide substitution from C (CGA for arginine) to T (TGA for stop codon). Both parents were heterozygous for this mutation. We used the new restriction site for endonuclease Fok-1 created by the mutation to detect this mutation in the genomic DNA of seven healthy family members. Four additional heterozygotes for the mutation were identified in two generations. Our data characterize for the first time the genetic defect of a selective and complete C1s deficiency in a Caucasian patient.

Age of Onset↗
PubMed2001

A new type of acquired C1 inhibitor deficiency associated with systemic lupus erythematosus.

Acquired C1 inhibitor (C1-INH) deficiency with consequent angioedema is a rare condition that may indicate an underlying lymphoproliferative disorder. The defect is caused by increased catabolism, which is often associated with the presence of serum autoantibodies to C1-INH. The present report describes 3 patients with systemic lupus erythematosus who developed typical symptoms of acquired angioedema, characterized by recurrent swelling of subcutaneous and mucous tissues. The 3 patients demonstrated a major classical pathway-mediated complement consumption, with very low levels of C3 antigen and decreased levels of C1-INH antigen. Neither antibodies to C1-INH nor associated lymphoproliferative disease was found. No patient had clinical and biologic signs of lupus activity at the time the angioedema occurred. All patients were treated with steroids and exhibited a good response, without relapse of angioedema and with normalization of plasma levels of C1-INH. In lupus patients who present with an angioedema syndrome, acquired or hereditary angioedema must be sought by examining parameters of the classical pathway and levels of C1-INH. Our observations suggest the existence of a new form of acquired C1-INH deficiency associated with a major classical pathway-mediated complement consumption and systemic autoimmunity.

Adolescent↗
PubMed2001

Successful plasma therapy in hemolytic uremic syndrome with factor H deficiency.

A patient with homozygous factor H deficiency presented with hemolytic uremic syndrome (HUS) at the age of 7 months. After a 2-year period of stability, renal failure and erythrocyte fragmentation recurred between the age of 3 and 4 years. Fresh frozen plasma infusions allowed renal function to be improved and erythrocyte fragmentation to be stopped. Withdrawal of plasma therapy led to a relapse of the biological signs of HUS.

Complement Factor H↗
PubMed1999

Functional properties of soluble CD21.

Soluble receptors may display immunoregulatory properties by blocking interactions between ligands and their membrane receptors or by triggering specific biologic responses through interaction with counter part membrane receptors. A natural soluble form of CD21 that is cleaved from lymphocyte membrane CD21 circulates in normal human serum. Soluble CD21 retains the capacity to bind iC3b and CD23, the known ligands of membrane CD21. In a similar fashion to IgE complexes, another ligand of CD23, the soluble CD21 was shown to efficiently trigger CD23-signalling pathways in human monocytes. By inducing release of proinflammatory cytokines and upregulating expression of molecules involved in antigen presentation, soluble CD21 modulates critical monocyte functions that may be relevant to allergic and inflammatory disorders.

Humans↗
PubMed1999

Expression of CD21 is developmentally regulated during thymic maturation of human T lymphocytes.

CD21, the C3d/CD23/Epstein-Barr virus (EBV), receptor is expressed at low density on cells of the T lineage. Immature thymocytes express CD21 with high density. In the present study, we have analyzed the expression of CD21 during intrathymic maturation of T cells. An intense staining for CD21 was observed at the double-negative stage and at the stage of early acquisition of CD4. CD21 expression was decreased at the double-positive and single-positive stages, to then reach levels similar to those of peripheral blood T cells. Staining of thymus sections showed a bright fluorescent signal on thymocytes entering the thymus in the cortical region. Taking advantage of the immature phenotype of cells expressing high amounts of CD21 (CD21(++)), we depleted thymocyte suspensions in CD3(+) and CD8(+) cells to study the properties of CD21 on this cell subset. Triggering of CD21 with its ligands iC3b, CD23 and anti-CD21 mAb did not alter the proliferative response of thymocytes to IL-7, and did not induce the differentiation of early cells into CD4(+)CD8(+) thymocytes. Immunoprecipitation did not reveal any molecule associated with CD21 that could play a signaling role in thymocytes. Finally, EBV induced a down-regulation of CD21 and an up-regulation of CD1 in CD21(++) thymocytes. Taken together, our observations demonstrate a regulated expression of CD21 on human thymocytes and suggest that the CD21(++) subset may be a target for EBV. We further suggest that CD21 on early thymocytes acts as a ligand for CD23-expressing cells in the thymus.

Cell Differentiation↗
PubMed1998

Soluble CD21 induces activation and differentiation of human monocytes through binding to membrane CD23.

Interactions between CD23, the low-affinity receptor for IgE, and CD21, the C3d/EBV receptor, modulate several intracellular events in lymphocytes. A soluble form of CD21 (sCD21) corresponding to the extracellular domain of the receptor circulates in normal plasma. We now demonstrate that purified sCD21 acts as a functional ligand for CD23-expressing monocytes. Soluble CD21 induced an increase in intracellular cGMP levels and the production of IL-6 and TNF-alpha in IL-4-pretreated monocytes induced to express CD23 but not in unstimulated CD23- monocytes. The accumulation of cGMP and the production of TNF-alpha were inhibited by NG-monomethyl-L-arginine (L-NMMA), indicating that sCD21 activates the L-arginine pathway of NO production. We demonstrated that sCD21 activates NO synthase (NOS) since it was found to enhance the conversion of L-arginine into L-citrulline and induce the intracellular expression of inducible NOS in CD23+ monocytes. In addition, sCD21 was shown to up-regulate the expression of HLA-DR and CD40 and decrease that of CD14 on cultured CD23+ monocytes. Thus, in a fashion similar to IgE complexes, sCD21 is able to efficiently trigger CD23 signaling pathways, inducing the release of pro-inflammatory mediators by human monocytes. Soluble CD21 up-regulates the expression of molecules involved in antigen presentation, further suggesting a potential immunoregulatory function for the soluble molecule.

Antigen Presentation↗
PubMed1998

Soluble CD21 (sCD21) forms biologically active complexes with CD23: sCD21 is present in normal plasma as a complex with trimeric CD23 and inhibits soluble CD23-induced IgE synthesis by B cells.

A soluble form of CD21 (sCD21) of 135 kDa is spontaneously released by human B and T lymphocytes upon shedding of the extracellular domain of the molecule. By Western blotting, we have now identified two forms of sCD21 of Mr 135 and 90 kDa in normal human serum. We further demonstrate that sCD21 circulates in a complexed form with cleavage fragments of C3 and CD23, two previously identified ligands of the membrane CD21 receptor. The CD23 molecule was in the form of a trimer in the soluble complex purified from plasma by affinity chromatography on anti-CD21 Sepharose. The serum sCD21 complex was also found to contain IgE. The presence of IgE and of CD21 in a soluble complex that contains trimeric CD23 as the only form of soluble CD23 (sCD23) is in agreement with a model in which two of the three lectin heads of CD23 bind to the Cepsilon3 domain of IgE, thus leaving one of the heads available for interaction with CD21. We further demonstrate that sCD21 inhibits sCD23-induced IgE synthesis by IL-4-stimulated B cells. The results indicate that sCD21 in plasma retains the ligand-binding properties of the membrane CD21 receptor and exhibits immunoregulatory properties that may be relevant to allergic and inflammatory disorders.

B-Lymphocytes↗
PubMed1996

Human lymphocytes shed a soluble form of CD21 (the C3dg/Epstein-Barr virus receptor, CR2) that binds iC3b and CD23.

We report on a soluble (s) form of CD21 (the C3dg/Epstein-Barr virus receptor, CR2) that is spontaneously released by B and T lymphocytes. Immunoprecipitation with anti-CD21 mAb of culture supernatants of surface and biosynthetically labeled B and T cell lines revealed a single band with an apparent molecular mass of 135 kDa. The molecule exhibited a molecular mass 10 kDa lower than that of membrane CD21. The release of soluble CD21 (sCD21) was time dependent and correlated with a parallel decrease in the expression of the membrane-associated molecule. The protein was also found in culture supernatants of tonsillar B cells and normal human thymocytes. Epitopic analysis using combinations of anti-CD21 monoclonal antibodies (mAb) indicated that sCD21 and membrane CD21 were similarly recognized by mAb directed against short consensus repeats (SCR) 1-2, SCR 4-5 and SCR 9-11. Affinity-purified sCD21 was capable of binding to purified human iC3b and to human recombinant CD23, as assessed by enzyme-linked immunosorbent assay and by using the BIAcore technology. In addition, normal human serum was found to contain a soluble form of CD21 that exhibited a similar molecular mass to that of the molecule shed by B and T cells in culture. The serum form of CD21 was recognized by all anti-CD21 mAb that we tested and showed a high reactivity with mAb directed against SCR 1-2. Our observations suggest that B and T cells shed the extracellular portion of CD21 and release a soluble molecule that retains the ligand-binding properties of CD21, thus having a potential role in immunoregulation.

B-Lymphocytes↗
PubMed1996

Autoantibodies to the collagen-like region of C1q are strongly associated with classical pathway-mediated hypocomplementemia in systemic lupus erythematosus.

We have investigated the presence of autoantibodies to the collagen-like region (CLR) of C1q and its relationship with classical pathway-dependent hypocomplementemia in patients with SLE. Antibodies to CLR/C1q were quantitated in the plasma of 113 unselected patients with SLE by ELISA, using purified CLR as antigen. Plasma concentration of C3, CH50 activity and C2 hemolytic activity were determined according to standard procedures. The prevalence of IgG antibodies to CLR/C1q in the study population was 33.6%. Plasma titers of anti-CLR/C1q autoantibodies showed a strong negative correlation with CH50 activity (p < 0.0001) and with plasma levels of C3 (p < 0.0001). Eighty-five percent of patients with severe complement consumption exhibited high titers of anti-CLR/C1q antibodies in plasma, independently of clinical disease activity. Anti-CLR/C1q antibodies were present in the plasma of 38% of patients with moderate classical pathway consumption and 14% of patients with no evidence of complement consumption. Analysis of sequential samples from six patients over a period of 18 to 24 months demonstrated that changes in CH50 activity mirrored those of the plasma titers of anti-CLR/C1q antibodies. Acquired hypocomplementemia through the classical pathway is strongly associated with the presence of anti-CLR/C1q autoantibodies in SLE. The results suggest that anti-CLR/C1q antibodies may perpetuate classical pathway activation, independently of clinical disease activity.

Autoantibodies↗
PubMed1995

[Partial properdin deficiency revealed by a septicemia caused by Neisseria meningitidis].

Properdin is one of the regulatory proteins of the alternative pathway of the complement system. Human properdin deficiency is an X-linked disorder strongly predisposing to meningococcal disease. Total deficiency (type I), partial deficiency (type II), and deficiency due to a dysfunctional molecule (type III) can be differentiated immunochemically. Four males in a family showed a selective partial deficiency of properdin. These individuals had 10% of normal properdin concentration in plasma, as measured by ELISA, while the other complement components were normal. Two of the properdin-deficient individuals in two generations had meningococcal infections. Two were clinically healthy at the time of investigation. Measurement of plasma levels of properdin has to be performed in the case of Neisseria meningitidis, especially where there is a previous history of severe bacterial infections in the same family as measurement of CH50 activity is ineffective for screening properdin deficiency.

Bacteremia↗
PubMed1994

Hypocomplementaemia of poststreptococcal acute glomerulonephritis is associated with C3 nephritic factor (C3NeF) IgG autoantibody activity.

We have observed that decreased plasma levels of C3 in the serum of three children with poststreptococcal acute glomerulonephritis (PSAGN) at the time of presentation were associated with the presence of C3NeF activity in purified serum IgG from the patients. C3NeF activity was determined using a sensitive assay measuring the ability of patients' IgG to stabilize a preformed cell-bound alternative pathway convertase complex. C3NeF activity of patients' IgG decreased within weeks as plasma levels of C3 progressively returned to normal values. C3NeF activity became undetectable within 1-4 months following normalization of plasma C3 levels. Our observations suggest that early alternative pathway-dependent hypocomplementaemia, a cardinal feature of PSAGN, is mediated by the transient expression of C3NeF autoantibody activity by patients' IgG.

Acute Disease↗
PubMed1994

Selective disappearance of C3NeF IgG autoantibody in the plasma of a patient with membranoproliferative glomerulonephritis following renal transplantation.

The serum of patients with membranoproliferative glomerulonephritis (MPGN) often exhibits C3 nephritic factor activity (C3NeF) associated with autoantibodies directed against the C3bBb alternative complement pathway C3 convertase. In the present study, we have sequentially assessed C3NeF activity in the purified IgG fraction of the serum of a patient with MPGN type II and end-stage renal disease every month for 1 year following renal transplantation and bilateral nephrectomy. C3NeF activity in the patient's purified serum IgG decreased with time from the first month after transplantation and became undetectable after forty-five weeks. At that time, plasma levels of C3 and factor B had returned to normal values. The disappearance of C3NeF activity in patient's IgG was selective in that no change in activity of two other autoantibodies and of one antibody against a non-self antigen was observed with time, indicating that the decrease in C3NeF activity was not related to a non-specific effect of immunosuppressive therapy. Loss of C3NeF activity was not related to the generation of anti-idiotypic antibodies against C3NeF. This study documents for the first time the selective disappearance of C3NeF activity following renal transplantation and bilateral nephrectomy. The results suggest that the autoantibody represents an antigen-driven expansion of self reactive B cell clones in response to a specific disease process in the kidney of patients with MPGN.

Adult↗
PubMed1994

[Exploration of the complement system in clinical practice].

The complement system plays an important role in defence of the host against infection and in the clearance of immune complexes. Defects in complement proteins are often associated with infections or auto-immune/immune complex diseases. Investigation of complement is useful for diagnosis and following of autoimmune diseases. Hypocomplementemia may result from genetic deficiency and/or consumption through activation of the system. In the particular case of angioneurotic oedema, laboratory data are essential to confirm the diagnosis and to the follow-up of the patients. Inappropriate activation of the complement system associated with the release of inflammatory mediators contributes to the tissue damage.

Child↗