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B Uring-Lambert

Publications and source records attributed to B Uring-Lambert.

At least 19 recordsLinked to original sources
PubMed2006

Which complement assays and typings are necessary for the diagnosis of complement deficiency in patients with lupus erythematosus? A study of 25 patients.

INTRODUCTION: Deficiencies in components of the classical pathway of complement activation are strong risk factors for lupus erythematosus (LE).Yet, it has not been addressed whether the conventional measurements of the serum hemolytic CH50 activity and antigenic concentrations of C3 and C4 are sufficient to asses a deficiency in C4A, C4B or C2 components, the most common deficiencies associated with LE. PATIENTS AND METHODS: In a retrospective series, we performed complement analyses in 35 patients with LE who were systematically screened for a complement deficiency. The majority of patients had cutaneous LE with mild systemic involvement and no complement consumption. Of 25 patients (72%) with complement deficiency we found 13 with a partial C4A deficiency, 2 with a complete C4A deficiency, 6 with a partial C4B deficiency, 2 with a complete C4B deficiency and 2 with a combined partial C2 and C4A deficiency. RESULTS: The total complement activity (CH50) was decreased in only one out of two patients with complete C4B deficiency. CH50 level was found to be low-normal (35-38 U/ml(-1)) in one patient with partial C4B deficiency, one patient with complete C4B deficiency and both patients with combined partial C4A and C2 deficiency. Total C4 levels were normal in 9 out of 13 the patients with a partial C4A deficiency and in 2 out of 6 patients with a complete C4B deficiency. The antigenic concentration of C3 was low in only 1 patients with a complete C4B deficiency and within the normal range in all the others patients. Overall, 50% of the patients had normal or elevated C3, C4, and CH50 levels. DISCUSSION: This study emphasizes that the usual measurements of CH50, C3 and C4 levels are not adequate to detect a C4 and/or C2 deficiency in patients with LE. In epidemiologic or investigative studies addressing the prevalence of complement deficiency, more elaborated diagnostic tests, such as C4 protein allotyping, C2 level measurement and genetic screening for type I C2 deficiency should also be performed.

Adult↗
PubMed2006

Inhaled formaldehyde exposure: effect on bronchial response to mite allergen in sensitized asthma patients.

BACKGROUND: Formaldehyde, an indoor air pollutant, is known to be an irritant and an etiologic factor in occupational asthma. An epidemiologic study suggests that it may also increase the risk of childhood asthma for concentrations above 60 microg/m(3). AIM: To evaluate the influence of pre-exposure to low-dose formaldehyde (100 microg/m(3) in 30 min according to the World Health Organization's recommended maximum value for indoor environments) on bronchial response to Dermatophagoides pteronyssinus. METHOD: Nineteen asthmatic subjects were included. Each subject underwent a mite allergen bronchial challenge test immediately after a standardized exposure in a chamber to formaldehyde or air (random order). Induced sputum were collected 24 h before and after mite challenge. RESULTS: After formaldehyde inhalation, patients developed an immediate bronchial response at a significantly lower dose of mite allergen than after air exposure (the geometric mean PD(20) for Der p 1 was 34.3 ng after formaldehyde and 45.4 ng after placebo, P = 0.05). The late-phase reaction, expressed as the maximum fall in forced expiratory volume in 1 s (FEV(1)) from baseline, was significantly higher after formaldehyde (15%vs 11%, P = 0.046). CONCLUSION: Our study demonstrated that exposure to low levels of formaldehyde significantly enhanced bronchial responsiveness to mite allergen in mite-sensitized subjects with asthma.

Adult↗
PubMed2006

[The bronchial response to inhaled formaldehyde].

INTRODUCTION: Formaldehyde is an ubiquitous indoor chemical polutant. Occupational exposure to high concentrations has revealed its irritant and allergenic potential. Nevertheless, domestic exposure to low concentrations may also have an effect on respiratory health in a non-specific way, just as has been found for other pollutants. STATE OF KNOWLEDGE: Potentiation of the response to allergens has been observed in animals and children. This effect has also been found on respiratory symptoms, with a 39% increase in the risk of asthma for a domiciliary exposure of more than 60 microgrammes.m(-3). We have recently been able to show, in a study with asthmatics sensitised to house dust mite, that the response to allergen provocation was increased following a 30 minutes exposure to 100 microgrammes.m(-3) formaldehyde. VIEWPOINT AND CONCLUSIONS: All the data show that mild exposure to formaldehyde in the home is sufficient to provoke sensitisation and also an aggrevation of symptoms in patients with allergic asthma. Taking into account the published evidence it is advisable that the concentrations of formaldehyde in domestic products should be made known in order to improve domiciliary air quality.

Air Pollution, Indoor↗
PubMed2005

The combination of complement deficiency and cigarette smoking as risk factor for cutaneous lupus erythematosus in men; a focus on combined C2/C4 deficiency.

BACKGROUND: Although deficiencies in the early components of the complement system were among the first identified genetic risk factors for systemic lupus erythematosus (SLE), only a few studies addressed their significance in patients with cutaneous LE (CLE). Among environmental factors, it was postulated that cigarette smoking might intervene in the pathogenesis of LE. OBJECTIVES: To describe the clinical and biological features of patients with CLE and a complement deficiency. A secondary objective was to assess cigarette smoking in patients with CLE. PATIENTS AND METHODS: A retrospective study including all patients diagnosed as having LE between 1995 and 2003 in the Dermatology Department of Strasbourg University Hospital. Patient charts were reviewed and those patients in whom a C4 and/or C2 deficiency was diagnosed were included. Two patients with a combined C2/C4 deficiency were analysed in detail. RESULTS: There were 48 females and 37 males (F/M ratio = 1.3), with a mean age of 41 years at diagnosis; 73% of the patients had chronic LE and 27% subacute CLE. Among 32 screened patients, 24 patients with a mean age of 36 years had a complement deficiency; 17 had a C4A deficiency, five a C4B deficiency and two a combined C4A/C2 deficiency. A high proportion (58%) of these patients was male; 82% of the patients were smokers. This was especially true in males: 94% were smokers compared with 69% of females. CONCLUSIONS: Partial deficiency of C4, C2 or C4 and C2 is a common finding in patients with CLE. Most male patients with CLE are smokers. It is thus suggested that the combination of cigarette smoking and complement deficiency could be a risk factor for LE in men.

Adolescent↗
PubMed2000

Lupus erythematosus associated with genetically determined deficiency of the second component of the complement.

BACKGROUND: The gene deletion responsible for the type I human complement C2 deficiency was reported in 1992. The purpose of our study is to evaluate clinical and immunological characteristics of 11 patients with lupus erythematosus and type I C2 deficiency. OBSERVATIONS: We observed 5 patients with a homozygous C2 deficiency and 6 with a heterozygous C2 deficiency. Eight patients had systemic lupus erythematosus, 2 had subacute cutaneous lupus erythematosus, and 1 had chronic lupus erythematosus. Photosensitivity was present in 73% of the patients, and 64% tested positive for anti-Ro (SSA) antibodies. Renal involvement that required immunosuppressive therapy was present in 54% of the patients. Ninety percent of the patients tested positive for antinuclear antibodies, and 54% tested positive for anti-double-stranded DNA antibodies. Phenotyping of the fourth component of the complement was performed in 82% of the patients and showed a C4A4B2 phenotype, which is suggestive for the type I C2 deficiency. CONCLUSIONS: Most patients with lupus erythematosus associated with C2 type I deficiency are photosensitive, and this is probably related to the presence of anti-Ro (SSA) autoantibodies. The prognosis for those patients is not better than that for patients with lupus erythematosus in general.

Adolescent↗
PubMed1999

Frequent factor II G20210A mutation in idiopathic portal vein thrombosis.

BACKGROUND & AIMS: Despite extensive investigations of portal vein thrombosis, no underlying cause is identifiable in up to 30% of patients. A recently described mutation of the prothrombin gene at nucleotide position 20210 is associated with history of venous thrombosis and was assessed in this study. METHODS: We compared the frequency of factor II G20210A and factor V G1691A (factor V Leiden) mutations in 10 patients with idiopathic portal vein thrombosis, 10 patients with nonidiopathic portal vein thrombosis, 60 patients with deep vein thrombosis of the legs, and 42 control subjects. RESULTS: The frequency of factor II G20210A mutation was increased in patients with idiopathic portal vein thrombosis (40.0%; confidence interval, 3.1%-76.9%) compared with controls (4.8%; confidence interval, 0%-11.5%) or patients with nonidiopathic portal vein thrombosis or deep vein thrombosis (P = 0.0001). In contrast, the frequency of the factor V G1691A mutation was similar in subjects with portal vein thrombosis and in controls but was increased in patients with deep vein thrombosis (P = 0.0001). CONCLUSIONS: The factor II G20210A mutation is frequent in patients with idiopathic portal vein thrombosis and should therefore be assessed under this circumstance.

Adult↗
PubMed1997

Combined heterozygous deficiency of the classical complement pathway proteins C2 and C4.

Genetic deficiencies of components of the classical pathway of complement activation are associated with an increased risk for the development of autoimmune and immune complex-mediated diseases. In the present study we report on the molecular and clinical features associated with combined heterozygous C4 and C2 deficiency in 15 individuals investigated within six families. Approximately 30% of the individuals manifested SLE or another autoimmune condition. Heterozygous C2 deficiency was related to a 28-bp deletion in the C2 gene (C2 deficiency type I), in most cases within the HLA-A25 B18 C2Q0 BfS C4A4B2 DR2 haplotype. Among 13 partial C4-deficient haplotypes transmitted, 8 carried C4A*Q0 alleles and 5 C4B*Q0 alleles. In seven cases the C4A*Q0 alleles were associated with a deletion of the C4A/CYP21P genes within the HLA-B8 C2C BfS C4AQ0B1 DR3 haplotype. In three cases, the C4B*Q0 allele was associated with a deletion of the C4B/CYP21P genes within the HLA-B18 C2C BfF1 C4A3BQ0 DR3 haplotype. In the other cases, C4A*Q0 or C4B*Q0 was dependent on as yet uncharacterized defects in the C4 gene or in C4 gene expression. In view of the relatively high frequency of heterozygous C4 deficiency in the normal Caucasian population, the expected frequency of the combined deficiency should approximate 0.001.

Adult↗
PubMed1996

Recurrent hematuria: a novel clinical presentation of hereditary complete complement C4 deficiency.

A 10-year-old boy suffered from recurrent attacks of fever, vomiting, and hematuria. During disease flares, circulating immune complexes were detected in the serum. Elevated levels of Bb, Ba, and C3a indicated complement activation through the alternative pathway. Complement C4 was undetectable. C4 phenotyping by agarose gel electrophoresis showed complete C4 deficiency. Restriction fragment length polymorphism (RFLP) studies showed a homozygous deletion of the C4B and 21-hydroxylase A genes. A mild mesangioproliferative glomerulonephritis with mesangial deposits of immunoglobulin (1g) G, IgM, IgA, Clq, C3, properdin, and terminal complement complex was probably caused by immune complex deposition and alternative complement pathway activation. Treatment with low-dose prednisolone substantially reduced the frequency of further episodes.

Biopsy↗
PubMed1996

Complement C4 phenotypes in patients with end-stage renal disease.

The phenotypes of complement C4 were determined by agarose gel electrophoresis in 130 patients with end-stage renal failure of various causes and compared with those of 140 healthy controls. C4 allotype frequencies did not differ between patients and controls. Null alleles of both isotypes C4A and C4B were increased, but also without reaching significance. In type 1 diabetics an increased frequency of C4AQ0 (25 vs. 11.8%, p < 0.05) was found. Patients with two null alleles were far more frequent in the group with insulin-dependent diabetes mellitus (25 vs. 3.6%, p < 0.01). We confirmed the presence of a previously described uremic variant of C4B1. Additional uremic variants of C4 were detected in uremic patients homozygous for C4A3, B2 and B3. The relative electrophoretic migration values of the uremic variants of C4A3, B1, B2 and B3 were 132.1 +/- 2.9, 35.8 +/- 1.5, 70.4 and 73.9. These variants appear early in the course of chronic renal failure and disappear after successful renal transplantation. Uremic variants are the only acquired C4 phenotypes known so far. How uremia causes these variants remains unclear, but probably involves carbamylation of the C4 molecule.

Alleles↗
PubMed1995

Immunogenicity of intraperitoneal insulin infusion using programmable implantable devices.

Intraperitoneal insulin infusion using implantable devices in insulin-dependent diabetic (IDDM) patients is promising since it improves diabetic control and decreases frequency of hypoglycaemia. However, preliminary data show a striking increase in plasma levels of anti-insulin antibodies with this therapy. In order to more precisely evaluate the immunogenicity and its consequences, anti-insulin antibody levels in 62 IDDM patients were assessed every 3 months during a 2-year period following pump implantation. At the same time, diabetes control was evaluated with HbA1c, mean blood glucose levels, standard deviation of the daily blood glucose levels and the frequency of low blood glucose (< 3.58 mmol/l). Factors involved in antibody formation such as age, gender, HLA typing, and complement C4 alleles were also studied. After implantation, anti-insulin antibody levels increased significantly from 3.14% (range 0-26%) to 8.34% (0-49%) after 1 year and remained elevated. Patients were divided into two groups: responders able to show at least one antiinsulin antibody titre higher than 15% and non-responders whose titres were always lower than 6%. None of the factors studied was shown to statistically influence the anti-insulin antibody titres. Non-responders had significantly better metabolic results than the responders. Severe hypoglycaemic episodes decreased dramatically in both groups. Insulin requirements were comparable at time 0 and decreased initially in both groups. They remained low for the non-responders but returned to pre-implantation values for responders. Intraperitoneal insulin infusion led to a high immunogenetic response towards insulin in about half of the patients, leading to only moderately deleterious effects on metabolic control.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

[Changes in the polymorphism and concentrations of components of the class II complement after orthotopic transplantation of the liver].

OBJECTIVES AND METHODS: The genes of complement factor B, C2 and C4 are located within the major histocompatibility complex class III region on chromosome 6 in man. These components demonstrate a genetic polymorphism which, when determinated, can be used to define complotypes (association of C2, factor B, C4A and C4B allotypes). On the other hand the liver is the main source of the circulating complement component synthesis. The aim of this study was to analyse the kinetics of several complement component (C3, factor B and C4) concentrations in the plasma and to assess changes in the polymorphic pattern of the complotypes after orthotopic liver transplantation. Nephelometry was used for plasma level measurements and factor B, C2 and C4 typings were performed with high voltage electrophoresis or isofocalisation and immunofixation at intervals before, during and after orthotopic liver transplantation in eleven patients. RESULTS: Complotypes changes were observed 24 hours after liver transplantation in all patients. A slight decrease in C3, C4, and factor B plasma levels was observed in the first hours after transplantation. A rapid increase in the levels of these components was observed subsequently, with normalization in less than 15 days. CONCLUSION: These results demonstrate a rapid synthesis of complement components and the changes in complement polymorphic patterns after liver transplantation.

Adult↗
PubMed1994

Complete inherited deficiency of the fourth complement component in a child with systemic lupus erythematosus and his disease-free brother in a north African family.

Although null alleles of complement C4 genes (C4A*Q0 and C4B*Q0) are frequent in the normal population, the occurrence of two null alleles on the same chromosome is very rare and therefore complete C4 deficiency is exceptional. We describe a 16-year-old North African boy who presented with systemic lupus erythematosus with renal involvement and persistent undetectable classical pathway activity and C4 protein and hemolytic activity in plasma, with normal C3 levels. Similar complement abnormalities were observed in his healthy 12-year-old brother. Complete C4 deficiency was documented in the two brothers by investigation of the family and the lack of C4A and C4B bands upon phenotyping of C4. Southern blot analysis of the C4/CYP21 gene organization in the family indicated that the deficiency resulted from a deletion of the C4B/CYP21A genes associated with nonexpression of a C4A gene. The double-null haplotype was found to be associated with homozygous A2 B17 C2C BFF C4 AQ0 BQ0 DR7 HLA haplotype. Thus, similar C4 deficiencies with HLA identity may lead to different clinical presentations.

Adolescent↗
PubMed1993

Complement component C4 deficiencies and gene alterations in patients with systemic lupus erythematosus.

Deficiency of complement component C4 is considered playing a role in the genetic predisposition for systemic lupus erythematosus (SLE). The purpose of this study was to characterize the genomic alterations of the C4 and CYP21 genes in 40 caucasoid patients with SLE by C4 allotyping and by RFLP analysis. Nineteen patients (47.5%) carried C4A null alleles and eight patients (20.0%) C4B null alleles. SLE patients had more frequent C4A null alleles (47.5%) than healthy individuals (20%) (chi 2 = 10.75; P < 0.005). The commonest molecular alteration in the patients with C4A null alleles was a large gene deletion affecting both C4A and CYP21A genes. However, among the patients with C4A null alleles, 16.7% persons had no detectable C4A deletion. The non-expression of C4A gene might be due to defects at various levels of gene expression (i.e. transcription and translation). Among the patients with C4B null alleles, 62.5% persons had no detectable gene lesion, whereas 37.5% showed a C4B deletion including both C4B/CYP21A or C4B/CYP21B genes. Duplication of the C4B gene was not rare in SLE patients, as we found 15.0% of the patients with a heterozygous C4B/CY21A gene duplication. The patients typed as having C4B gene homoduplication (B1,1) demonstrated two long C4B loci, whereas heteroduplication (B1,2) displayed two short loci, therefore the type of C4B gene duplication may be related to the gene length. In conclusion, C4 deficiencies observed in 26 of the 40 SLE patients studied were very heterogeneous. In every case, the gene alteration affected both C4 and CYP21 genes.

Alleles↗
PubMed1992

[11th International Histocompatibility Workshop 1991: Personal data for the Multiple Sclerosis Study].

In our multiple sclerosis (MS) study as a part of the 11th IHWS we HLA-typed 6 MS families with 9 patients and defined the complement polymorphisms (BF, C2, C4) of these families. The aims of the study were the definition of the MS susceptibility gene and the investigation of the involvement of other factors in the etiopathogenesis of MS. The MS study of the IHWS demonstrated a strong association with HLA-DRw15 and -DWw6 in a Caucasian population. The heterozygous C2 deficiency in our family PD1 linked with the haplotype A25 B18 DR2 BFS C4A4 C4B2 confirmed by complement titration may express the participation of complement factors in the etiopathogenesis of MS resulting in immunogenetic heterogeneity of MS. Analysis of the 3 MS pairs of sisters shows the linkage of HLA with the assumed MS susceptibility gene. This could not be confirmed in the whole MS family study of the 11th IHWS.

Chromosome Mapping↗
PubMed1991

Clinical manifestations in humans of combined C7 and C4 deficiency associated with low levels of C2, C8, and C9.

64 members of a large kindred with inherited deficiency of the seventh component of complement, C7, were studied for plasma levels of antigenetic and functional components of complement as well as for clinical manifestations of infections and autoimmune diseases. Thirty-six individuals showed a low level of C2, C7, C8, and/or C9, including null alleles for C4A and C4B. Two subjects had a complete C7 deficiency. One of them concomitantly presented a low C2 level and a C4BQ0 allele. HLA allotyping strongly suggested C2 depression associated with a C4BQ0 allele. The 2 individuals with total absence of C7 suffered from fulminant disseminated meningococcal infections. The partial depression of one or more complement components associated with apparent good health. These results may indicate that simultaneous partial depressions of up to four complement components do not lead to clinical manifestation of infectious and autoimmune disease.

Adult↗
PubMed1990

A new duplication C4B*1,12 at the C4B locus associated with BF*S07 in a Tunisian population.

Twenty-five Tunisian families were analyzed for their complement alleles in order to detect duplications at the C4 loci. In this population, the most characteristic duplications are C4A2, B1.12 or C4A1, B1,12 always associated with BFS07 and C2C. This previously undescribed C4B1,12 duplication was found in seven families, five times in association with HLA-A2, B50.

Alleles↗
PubMed1990

C2 reference typing report.

Thirty samples contributed by seven laboratories to the VIth Complement Genetics Workshop were analyzed by isoelectric focusing and immunoblotting with a specific antihuman C2 antibody for the study of the polymorphism of native, activated and desialated C2. This study allowed to compare almost all the C2 variants so far described and also several 'new variants'. According to our results, the C2 system consists of nine structural variants at the protein level which include the common C2 C, the less common C2 B (in Caucasoids), four rare acidic and three rare basic variants. The polymorphic site for the basic variants is carried by the C2a fragment. Typing of desialated C2 is necessary to identify rare acidic or basic variants, especially the C2 BH and C2 BJ variants which seem difficult to be recognized in the native protein.

Antibodies↗