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S Caillat-Zucman

Publications and source records attributed to S Caillat-Zucman.

At least 19 recordsLinked to original sources
PubMed2006

[Pathophysiology of Behcet's disease].

SUBJECT: Pathophysiology of Behçet's disease (BD) is complex. Recent experimental data shed new light on the mechanisms leading to organ lesions. MAIN ISSUES: Neutrophils and cytotoxic lymphocytes are now recognized as key effector cells in BD. Genetic susceptibility, environmental factors (virus and/or bacterial infections), inflammatory response abnormalities (heat shock proteins, dysregulated NO production) and abnormal immune response play also a major role in BD pathogeny. PERSPECTIVES: Better understanding of the BD pathophysiology will allow the development of new therapies more specific of BD.

Behcet Syndrome↗
PubMed2005

Transient familial haemophagocytic lymphohistiocytosis reactivation post-CD34 haematopoietic stem cell transplantation.

Familial haemophagocytic lymphohistiocytosis (FHLH) is a genetic disorder caused by defective lymphocyte cytotoxicity, resulting in impaired lymphocyte homeostasis and macrophage infiltration of solid tissues and bone marrow, with extensive haemophagocytosis. It is invariably fatal unless treated by allogeneic haematopoietic stem cell transplantation (HSCT). In a retrospective analysis of 11 cases of FHLH, transplanted in one centre between January 1999 and December 2003, it was found that host T cell expansion occurred early after HSCT in a setting of a viral infection (cytomegalovirus and Epstein-Barr virus respectively) in two cases who received T cell-depleted HSCT. Transient recurrence of clinical and biological manifestations of FHLH was observed, despite evidence for donor cell engraftment. Secondary development of donor T cells led to stable mixed chimaerism and sustained remission of FHLH. Detection of host-derived T cells soon after HSCT in a patient with FHLH should thus not mistakenly be taken as a manifestation of graft rejection.

Antigens, CD34↗
PubMed2004

Impact of HLA matching on outcome of hematopoietic stem cell transplantation in children with inherited diseases: a single-center comparative analysis of genoidentical, haploidentical or unrelated donors.

SUMMARY: Hematological inherited diseases can be cured by hematopoietic stem cell transplantation (HSCT) from an human leukocyte antigen (HLA)-identical sibling donor (MSD), but the outcome of unrelated donors (URD) or haploidentical donors (HMD) has been a cause of concern. In all, 94 children affected with inherited diseases underwent HSCT at a single center using MSD (group A, n=31), URD (group B, n=23) or HMD (group C, n=40). There was no difference in the rate of engraftment or in the incidence of grades III-IV acute graft-versus-host disease (GVHD) between the groups. Survival rate was 80.6% in group A, 62.5% in group B and 47.5% in group C (P=0.023). In group B, survival rate was 73.7% in the subgroup with zero or one class I mismatch, and 25% in the subgroup with two or more class I mismatches (P=0.04). In group C, survival rate was 83.3% in the 9/10-identical subgroup, 64.3% in the seven or 8/10 subgroup, and 25% in the five or 6/10 subgroup (P=0.0007). Thus, engraftment, incidence of GVHD and survival are similar in recipients of grafts from MSD, URD with 0-1 class I-mismatch, or HMD with at least 7/10 HLA matches. The low success of HSCT using more disparate donors suggests reserving them for patients with very poor prognosis.

Adolescent↗
PubMed2004

Does haploidentical transplantation in children with primary immunodeficiencies have the potential to exploit donor NK cell alloreactivity?

Donor potential to exert NK cell alloreactivity has been shown to confer survival advantage in haploidentical hematopoietic cell transplantation for hematological malignancies. We investigated killer immunoglobulin receptor (KIR) ligand incompatibility in 40 children receiving haploidentical transplantation for primary immunodeficiencies. The conditioning regimen consisted of busulfan and cyclophosphamide. T-cell depletion of the graft used complement-dependent lysis or CD34+ selection. Two patients died in the first month. The remaining 38 patients were divided into those with (n=13) and those without (n=25) donor potential to exert NK cell alloreactivity. Engraftment was similar in the two groups (61.5 and 64%, respectively). The incidence of grade II-IV acute graft-versus-host disease (GVHD) tended to be lower in the group with donor potential to exert NK cell alloreactivity, but the difference was not significant. In conclusion, in this series of patients with primary immunodeficiencies, donor potential to exert NK cell alloreactivity was not associated with significant advantages in engraftment and prevention of acute GVHD.

Child, Preschool↗
PubMed2003

HLA-B phenotype modifies the course of Behçet's disease in Moroccan patients.

In Moroccan patients, predisposition to Behçet's disease is associated with HLA-B*51, mostly in males with young age at disease onset. In addition, the disease is associated with B*15 both in females and in males with late disease onset. We analyzed the clinical presentation, the severity and the course of the disease in 86 Moroccan patients according to their HLA-B phenotype. The presence of the B*51 or B*15 did not predispose to a particular clinical manifestation, nor to a more severe presentation of the disease. By contrast, outcome of the disease significantly differed depending on HLA-B phenotype, with an increase of symptoms in most B*51+ patients and in half of B*15 patients, and a remission or a decrease of symptoms in all B*51-B*15- patients. This variable course was mostly observed for ocular lesions, skin lesions, articular symptoms, and neurological symptoms. These data may suggest that treatment should be given early in the course of the disease in B*51 or B*15-positive patients in order to stabilize the inflammatory process.

Alleles↗
PubMed2002

HLA class I polymorphism in a Moroccan population from Casablanca.

We have studied the distribution of HLA-A and -B alleles and haplotypes by sequence-specific primer amplification in a sample of 100 unrelated healthy individuals belonging to both Berber and Arabic-speaking groups from the region of Casablanca in Morocco. Among the 17 HLA-A and 23 HLA-B alleles observed, the most frequent were HLA-A2 (21%), -A1 (11%), -A3 (10%), -B44 (11.4%), -B50 (9.9%), -B5(8.5%) and -B35 (6.5%). Six two-locus haplotypes were observed with a frequency above 5%: A2-B50 (9.6%), A23-B44 (7.4%), A2-B15 (6.4%), A68-B39 (5.3%), A1-B51 (5.3%) and A68-B44 (4.3%). Our data confirm that, on the basis of genetic distances, the majority of present-day North Africans from Morocco are closely related to Berbers and also to Iberians. They cluster apart from Middle-Eastern Mediterranean populations, and show greater genetic distances to Eastern and other Mediterranean populations. This study will serve as a reference for further anthropological studies, as well as studies of HLA and disease associations.

Evolution, Molecular↗
PubMed2002

Histological features and HLA class II alleles in hepatitis C virus chronically infected patients with persistently normal alanine aminotransferase levels.

OBJECTIVE: A significant proportion of individuals with chronic hepatitis C virus (HCV) infection have persistently normal alanine aminotransferase (ALT) levels. Although data are controversial, such patients usually have weaker histological damage and a lower progression rate of fibrosis. The aims of this study were: (1) to compare demographic, virological, and histological parameters of HCV patients with normal ALT values with those of HCV patients with elevated ALT levels; and (2) to determine whether HLA class II alleles contribute to the persistence of normal ALT levels in HCV patients. PATIENTS AND METHODS: Eighty three patients with chronic HCV infection and persistently normal ALT values (group 1) and 233 patients with chronic HCV infection and elevated ALT levels (group 2) were studied. Histological features were expressed using Knodell and Metavir scores. HLA DRB1* and DQB1* genotyping was performed using hybridisation with sequence specific oligonucleotides after genomic amplification. The kappa2 and Fisher's exact tests were used to compare discrete variables and phenotype frequencies between the two groups, and Wilcoxon's test was used for continuous variables. A multivariate logistic regression model was used to determine which variables predicted normal ALT values. RESULTS: ALT levels were correlated with the severity of liver damage. In group 1, 93% of patients had an F0 or F1 Metavir index of fibrosis compared with 47% of patients in group 2 (p<0.001). A longer duration of infection (p<0.001) and increased DRB1*11 phenotype frequency (pc=0.03) were observed among patients with normal ALT. The two groups did not differ with regard to the mode of contamination or viral genotype. After logistic regression, young age (p=0.0008), female sex (p=0.01), long duration of infection (p=0.0001), and HLA DRB1*11 (p=0.050) were more strongly associated with persistence of normal ALT. CONCLUSIONS: Our study confirms that patients with chronic hepatitis C and normal ALT levels have less severe liver disease than those with elevated ALT levels. This particular biochemical outcome may be explained, at least in part, by host immunogenetic factors such as the presence of HLA-DRB1*11.

Adult↗
PubMed2002

Anticardiolipin antibodies in patients with multiple sclerosis do not represent a subgroup of patients according to clinical, familial, and biological characteristics.

BACKGROUND: In multiple sclerosis (MS), case control studies have shown that anticardiolipin antibodies (aCL Ab) are more frequent than in the general population and that aCL Ab positivity may be associated with specific clinical characteristics. OBJECTIVES: To determine whether patients with MS who are positive for aCL Ab have specific characteristics. METHODS: 285 consecutive patients with MS were tested for aCL Ab positivity. Patients also underwent complete autoimmune screening and were systematically evaluated for clinical characteristics and individual or family history of autoimmune disease. RESULTS: aCL Ab positivity was found in 42 patients (15%). The main isotype was aCL IgM (32 patients, 11%). Demographics and clinical characteristics including sex, age at onset, course of the disease, expanded disability status scale score, and progression index were not different between aCL Ab positive and aCL Ab negative patients. Clinical systems involved at onset or during the course of the disease were not different from what is usually observed in MS. aCL Ab positivity was not associated with an increased frequency of autoimmune disease and was not predictive of a family history of autoimmune disease. Patients positive for aCL IgM were more frequently positive for the presence of non-organ specific antibodies (53% v 39%, respectively, p = 0.02). CONCLUSIONS: These results do not support the hypothesis that patients with MS with aCL Ab constitute a subgroup of MS according to demographic clinical and familial characteristics. The greater frequency of other antibodies in aCL Ab positive patients suggests that they only reflect a more general autoimmune activation in MS.

Adult↗
PubMed2001

Maternally inherited diabetes and deafness: a multicenter study.

BACKGROUND: Maternally inherited diabetes and deafness (MIDD), which is seen in 0.5% to 2.8% of patients with type 2 diabetes mellitus, is related to a point mutation at position 3243 of mitochondrial (mt) DNA. Its clinical description is incomplete. OBJECTIVE: To study the clinical presentation and complications of diabetes in patients with MIDD and to identify clinical characteristics that may help select diabetic patients for mtDNA mutation screening. DESIGN: Multicenter prospective descriptive study. SETTING: 16 French departments of internal medicine, diabetes and metabolic diseases, or both. PATIENTS: 54 patients with type 2 diabetes mellitus and the mtDNA 3243 mutation. MEASUREMENTS: Characteristics of diabetes, metabolic control (glycosylated hemoglobin level), complications of diabetes, and involvement of other organs. RESULTS: On average, patients with MIDD were young at diabetes onset and presented with a normal or low body mass index. None were obese. Seventy-three percent of probands had a maternal family history of diabetes. Diabetes was non-insulin-dependent at onset in 87% of patients; however, 46% of patients had non-insulin-dependent disease at onset but progressed to insulin therapy after a mean duration of approximately 10 years. Neurosensory hearing loss was present in almost all patients. Eighty-six percent of patients who received an ophthalmologic examination had macular pattern dystrophy (a specific retinal lesion). Forty-three percent of patients had myopathy, 15% had cardiomyopathy, and 18% (9 of 51) had neuropsychiatric symptoms. Although the prevalence of diabetic retinopathy was 8% among patients who received an ophthalmologic examination, lower than expected after a mean 12-year duration of diabetes, prevalence of kidney disease was 28%. This suggests that a specific renal involvement was the result of mitochondrial disease. CONCLUSIONS: Maternally inherited diabetes and deafness has a specific clinical profile that may help identify diabetic patients for mtDNA testing.

Adolescent↗
PubMed2001

Influence of HLA-DR phenotype on the risk of hepatitis C virus-associated mixed cryoglobulinemia.

OBJECTIVE: Circumstances predisposing hepatitis C virus (HCV)-infected patients to develop mixed cryoglobulinemia (MC), which may manifest as a small-vessel systemic vasculitis (MC vasculitis), remain unclear. Previous studies have failed to demonstrate a clear role of either viral factors (genotype, viral load) or host factors (lymphocytes or immunoglobulin subsets). This study was undertaken to examine a possible role of HLA class II alleles in HCV-associated MC. METHODS: One hundred fifty-eight HCV-infected patients, of whom 76 had MC (56 with type II MC and 20 with type III MC) and 82 did not have MC, were studied prospectively. MC vasculitis was noted in 35 HCV-infected patients with type II IgMkappa-containing cryoglobulins. HLA-DRB1 and HLA-DQB1 polymorphism was analyzed by hybridization using allele-specific oligonucleotides, after gene amplification. The odds ratio (OR) was calculated with Woolf's method. Then, using multivariate analysis, demographic, biologic, immunologic, virologic, and liver histologic factors associated with the presence of MC and MC vasculitis were investigated. RESULTS: HLA-DR11 was significantly more frequent in patients with type II MC than in those without MC (41.1% versus 17.1%; OR 3.4, corrected P [Pcorr] = 0.017), regardless of the presence of vasculitis accompanying the MC (37.1% of those with MC vasculitis, 34.1% of those with MC but no vasculitis). HLA-DR7 was less frequent in HCV-infected patients with MC than in those without MC (13.2% versus 30.5%; OR 0.34, P = 0.012, Pcorr not significant), with a particularly lower frequency in those with type II MC and those with MC vasculitis (12.5% and 8.6%, respectively). There was no significant difference in HLA-DQB1 distribution between the different patient groups. By univariate and multivariate analysis, HLA-DR11 was the only positive predictive factor, besides female sex and advanced age, for the presence of MC and HCV-associated MC vasculitis (OR 2.58). CONCLUSION: Our results indicate that the presence of the DR11 phenotype is associated with a significantly increased risk for the development of type II MC in patients with chronic HCV infection. In contrast, HLA-DR7 appears to protect against the production of type II MC. These results suggest that the host's immune response genes may play a role in the pathogenesis of HCV-associated MC.

Adult↗
PubMed2001

A dinucleotide repeat polymorphism at the poly(ADP-ribose) polymerase gene is not associated with predisposition to type 1 diabetes in French Caucasians.

The poly (ADP-ribose) polymerase (PARP) is a nuclear enzyme that detects and binds DNA strand breaks. Excessive PARP activation leads to the death of mice islet beta-cells by depleting cellular energy reserves. On the other hand, PARP-mutant mice are resistant to streptozotocine-induced diabetes, and in the non-obese diabetic (NOD) mouse model, treatment with nicotinamide, a PARP inhibitor, protects islet cells against cytotoxic actions in vitro and results in a decreased incidence of type 1 diabetes. PARP gene in human is located within a recently identified type 1 diabetes-susceptibility region on chromosome 1q41-42, and contains a polymorphic CA dinucleotide repeat in the promoter region. To consider the putative involvement of PARP polymorphism in predisposition to type 1 diabetes, we performed genotyping for the various alleles of the CA dinucleotide repeat in 158 unrelated French Caucasian patients with type 1 diabetes and 193 ethnically-matched healthy controls. We found no significant difference of PARP alleles distribution between patients and controls, even after stratification of the patients according to HLA class II genotype or to age at disease onset. Our results suggest that this PARP polymorphism does not influence susceptibility to type 1 diabetes in French Caucasians.

Adolescent↗
PubMed2001

HLA-B*51 and B*15 alleles confer predisposition to Behçet's disease in Moroccan patients.

HLA class I polymorphism in Moroccan patients with Behçet's disease has not been investigated so far. In this study, HLA-B* phenotype frequencies were analyzed in 86 unrelated Moroccan patients (45 males, 41 females) and 111 ethnically matched healthy controls. The predisposing effect of the B*51 was confirmed (30.2% in patients and 15.3% in controls, OR = 2.39, 95% CI [1.2-4.8], p = 0.015). It was mostly observed in males with young age at disease onset (OR= 5.5 [1.9-15.9], p = 0.002 compared to controls). The Moroccan BD group also presented a previously unknown association with HLA-B*15 (25.6% of patients versus 11.7% of controls, OR = 2.59 [1.2-5.5], p = 0.014), both in females and in males with late-onset of the disease. Altogether, the B*15 and/or B*51 alleles were expressed in 55.8% of patients compared to 27% of controls (OR = 3.4 [1.9-6.2], p < 10-4, Pc = 0.003). Our data indicate HLA-B effects on BD pathogenesis should be considered separately for men and women.

Adolescent↗
PubMed2001

Family-based association of HLA class II alleles and haplotypes with type I diabetes in Brazilians reveals some characteristics of a highly diversified population.

The association of HLA class II haplotypes with type I diabetes was analyzed in 56 Southeastern Brazilian families using affected family-based controls (AFBAC) method. DRB1-DQA1-DQB1 alleles were determined by polymerase chain reaction/sequence-specific primer genotyping. This study first revealed the great haplotype diversity of Brazilians (65 different haplotypes even with incomplete DRB1 subtyping), probably due to the admixture of Africans genes with European and Amerindian genes in this population. The results revealed increased frequencies of the DRB1*03-DQA1*0501-DQB1*02 and DRB1*0401-DQA1*03-DQB1*0302 haplotypes in the patient group The highest risk for type I diabetes was associated with the heterozygote DRB1*03/*04 genotype as largely reported, and DRB1*03/X and DRB1*04/Y genotypes conferred a significant, but much lower disease risk. Protection from type I diabetes revealed some peculiarities in Southeastern Brazilians: a lack of significant protecting effect of the DRB1*1501-DQA1*0102-DQB1*0602 haplotype, and an apparent protection conferred by the DRB1*13-DQB1*0301, DRB1*11-DQB1*0301, and DRB1*01-DQB1*0501 two-locus haplotypes. The risk to type I diabetes in the highly diversified Southeastern Brazilians evidenced specific information to the prediction of the disease in this region of the country.

Adolescent↗
PubMed2001

CTLA-4/CD 28 region polymorphisms in children from families with autoimmune hepatitis.

Susceptibility to autoimmune hepatitis is associated with particular human leucocyte antigen class II alleles. However, non-HLA genetic factors are likely to be required for development of the disease. Among the candidate genes, the cytotoxic T-lymphocyte antigen 4 (CTLA-4) and CD28 genes, located on chromosome 2q33 in humans, encode a cell surface molecule playing a dominant role in the regulation of T-cell activation. The CTLA-4 and CD28 polymorphisms were investigated in children from 32 families with autoimmune hepatitis (AIH). The transmission/disequilibrium test revealed increased transmission of the (AT)8 (dinucleotide repeat) and A (exon 1) alleles of CTLA-4 gene from heterozygous parents to affected offspring (87.5% and 83.5%) with type 1 AIH, compared with unaffected offspring (50.0% for both, p = 0.009 and 0.02, respectively). In contrast, no deviation in transmission for CTLA-4 polymorphisms was found between type 2 AIH patients and unaffected offspring. No evidence for association was found between CD28 gene polymorphism or D2S72 genetic marker and both types of AIH. This study identified the CTLA-4 gene polymorphism as a non-HLA determinant that predisposes to AIH type 1 in children. The genetic heterogeneity seen in the present study provides a new argument in favor of pathogenic differences between type 1 and type 2 AIH.

Abatacept↗
PubMed2001

Lack of evidence of a specific role for C4A gene deficiency in determining disease susceptibility among C4-deficient patients with systemic lupus erythematosus (SLE).

The aim of the present study was to investigate the prevalence of C4 and C2 deficiencies and to characterize genomic alterations in C4 genes in a large cohort of 125 unselected patients with SLE. We determined the protein concentration and functional activity of C2 and C4, as well as the C4 phenotype. C4 genotyping included Taq 1 restricted fragment lengh polymorphism (RFLP) analysis and polymerase chain reaction using sequence-specific primers (SSP-PCR). Type I C2 deficiency was diagnosed by PCR. Overall, 79.2% of the patients exhibited abnormalities of the C4 genes including deletion, non-expression, gene conversion and duplication. Among C4-deficient patients (n = 66, 52.8% prevalence), 41.0% of the patients exhibited a C4A deficiency and 59.0% a C4B deficiency. Half of the C4 deficiencies were due to a gene deletion. There was a strong association between C4A and C4B gene deletion and the presence of the DRB1*03 allele. Among the silent C4A genes, only two cases were related to a 2-bp insertion in exon 29 of the C4A gene. A gene conversion was demonstrated in eight patients (6.4%). One patient had a homozygous C4A deficiency. Three (2.4%) patients presented with a heterozygous type I C2 deficiency and none with homozygous deficiency. Our results argue against a specific role for C4A gene deficiency in determining disease susceptibility among patients with SLE that are C4-deficient.

Adolescent↗
PubMed2001

A common stromal cell-derived factor-1 chemokine gene variant is associated with the early onset of type 1 diabetes.

Type 1 diabetes results from the autoimmune destruction of pancreatic beta-cells. Although the disease shows a strong association with HLA class II alleles, other genes may influence the initiation or the rate of progression of the autoimmune process. The recruitment of mononuclear cells within the islets of Langerhans is a critical step in the pathogenesis of the disease. Because chemokines are cytokines that promote migration of mononuclear cells, we hypothesized that polymorphisms in chemokine receptor or chemokine genes, CCR5 and SDF1, may be involved in susceptibility to or clinical expression of type 1 diabetes. The frequencies of the CCR5-delta32 and SDF1-3'A (801G-->A in the 3' untranslated region) variants were similar in 208 unrelated Caucasian patients with type 1 diabetes and in 120 Caucasian control subjects. They were not modified after stratification for the predisposing HLA-DR3 and -DR4 haplotypes. However, the SDF1-3'A variant was strongly associated with early onset (< 15 years) of the disease (odds ratio 2.6, P = 0.0019). On average, the presence of the SDF1-3'A allele was associated with a 5-year reduction in the age at onset of diabetes (P = 0.0067). Our results suggest that stromal cell-derived factor-1 may be implicated in the aggressiveness of the autoimmune process leading to type 1 diabetes. These preliminary data require replication in other populations.

3' Untranslated Regions↗