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1.
Rev Neurol (Paris) ; 174(1-2): 56-65, 2018.
Article in English | MEDLINE | ID: mdl-28688606

ABSTRACT

OBJECTIVES: Unverricht-Lundborg disease (ULD) is the most common form of progressive myoclonus epilepsy. Cerebellar dysfunction may appear over time, contributing along with myoclonus to motor disability. The purpose of the present work was to clarify the motor and neurophysiological characteristics of ULD patients. METHODS: Nine patients with genetically proven ULD were evaluated clinically (medical history collected from patient charts, the Scale for the Assessment and Rating of Ataxia and Unified Myoclonus Rating Scale). Neurophysiological investigations included EEG, surface polymyography, long-loop C-reflexes, somatosensory evoked potentials, EEG jerk-locked back-averaging (JLBA) and oculomotor recordings. All patients underwent brain MRI. Non-parametric Mann-Whitney tests were used to compare ULD patients' oculomotor parameters with those of a matched group of healthy volunteers (HV). RESULTS: Myoclonus was activated by action but was virtually absent at rest and poorly induced by stimuli. Positive myoclonus was multifocal, often rhythmic and of brief duration, with top-down pyramidal temporospatial propagation. Cortical neurophysiology revealed a transient wave preceding myoclonus on EEG JLBA (n=8), enlarged somatosensory evoked potentials (n=7) and positive long-loop C-reflexes at rest (n=5). Compared with HV, ULD patients demonstrated decreased saccadic gain, increased gain dispersion and a higher frequency of hypermetric saccades associated with decreased peak velocity. CONCLUSION: A homogeneous motor pattern was delineated that may represent a ULD clinical and neurophysiological signature. Clinical and neurophysiological findings confirmed the pure cortical origin of the permanent myoclonus. Also, oculomotor findings shed new light on ULD pathophysiology by evidencing combined midbrain and cerebellar dysfunction.


Subject(s)
Unverricht-Lundborg Syndrome/physiopathology , Adolescent , Adult , Age of Onset , Ataxia/etiology , Ataxia/physiopathology , Brain/diagnostic imaging , Child , Electroencephalography , Electromyography , Evoked Potentials, Somatosensory , Eye Movements , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Myoclonus/diagnostic imaging , Myoclonus/physiopathology , Neurologic Examination , Oculomotor Muscles/physiopathology , Saccades , Unverricht-Lundborg Syndrome/diagnosis , Young Adult
2.
Data Brief ; 12: 400-404, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28491945

ABSTRACT

The data presented in this paper are reference ranges for frequencies of thirty-eight subpopulations of T, B and NK lymphocytes, established from a cohort of 253 healthy blood donors aged from 19 to 67. When relevant, the influence of age or sex was taken into account to calculate these reference values. This article is related to the research article entitled "Influence of age, sex and HCMV-serostatus on blood lymphocyte subpopulations in healthy adults" (Apoil et al., 2017) [1]. Immunophenotyping data obtained from each individual is made publicly available for extended analyses.

3.
Cell Immunol ; 314: 42-53, 2017 04.
Article in English | MEDLINE | ID: mdl-28219652

ABSTRACT

Using a standardized immunophenotyping procedure we studied thirty-eight distinct subpopulations of T, B and NK lymphocytes in 253 healthy blood donors aged from 19 to 67. We analysed the influence of age, sex and HCMV seropositivity on each lymphocyte subpopulations and established reference ranges. We observed that aging influences the largest number of lymphocyte subpopulations with a slow increase of CD8+ EMRA T lymphocytes and of the numbers of circulating Tregs. The proportion of HLA-DR+ cells among Tregs increased with age and was correlated to the proportion of HLA-DR+ cells among effector T CD4+ lymphocytes. Sex had a major impact on absolute counts of CD4+ T cells which were higher in females. HCMV-seropositivity was associated with higher frequencies of CD8+ EMRA memory T lymphocytes while a high frequency of terminally differentiated EMRA CD4+ T cells was observed in 80% of HCMV-positive individuals and in none of the HCMV seronegative individuals.


Subject(s)
Age Factors , Cytomegalovirus Infections/immunology , Cytomegalovirus/immunology , Lymphocyte Subsets/immunology , Sex Factors , T-Lymphocytes/immunology , Adult , Aged , Antibodies, Viral/blood , B-Lymphocytes/immunology , CD4 Antigens/metabolism , CD8 Antigens/metabolism , Cytomegalovirus Infections/epidemiology , Female , HLA-DR Antigens/metabolism , Healthy Volunteers , Humans , Immunophenotyping , Killer Cells, Natural/immunology , Lymphocyte Count , Male , Middle Aged , Prevalence , Reference Values
4.
Am J Transplant ; 17(2): 420-431, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27402017

ABSTRACT

The reasons for the increased incidence of de novo anti-human leukocyte antibody (HLA) donor-specific antibodies (DSAs) observed after kidney allograft nephrectomy are not fully understood. One advocated mechanism suggests that at graft loss, DSAs are not detected in the serum because they are fixed on the nonfunctional transplant; removal of the kidney allows DSAs to then appear in the blood circulation. The aim of our study was to compare anti-HLA antibodies present in the serum and in the graft at the time of an allograft nephrectomy. Using solid-phase assays, anti-HLA antibodies were searched for in the sera of 17 kidney transplant patients undergoing allograft nephrectomy. No anti-HLA antibodies were detected in the graft if they were not also detected in the serum. Eleven of the 12 patients who had DSAs detected in their sera also had DSAs detected in the grafts. Epitopic analysis revealed that most anti-HLA antibodies detected in removed grafts were directed against the donor. In summary, our data show that all anti-HLA antibodies that were detected in grafts were also detected in the sera. These intragraft anti-HLA antibodies are mostly directed against the donor at an epitopic level but not always at an antigenic level.


Subject(s)
Epitopes/immunology , Graft Rejection/etiology , HLA Antigens/immunology , Isoantibodies/blood , Kidney Transplantation/adverse effects , Nephrectomy/adverse effects , Tissue Donors , Adult , Alleles , Allografts , Female , Graft Survival , Humans , Male
5.
Clin Exp Allergy ; 46(1): 133-41, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26767494

ABSTRACT

BACKGROUND: Mastocytosis is difficult to diagnose, especially when systemic mast cell activation symptoms are not present or involve only one extracutaneous organ. OBJECTIVE: The main objective was to evaluate the accuracy of the bone marrow tryptase level in the diagnosis of systemic mastocytosis in patients with a clinical suspicion of mastocytosis. METHODS: We included all adult patients evaluated in our centre between December 2009 and 2013 for suspected mastocytosis as part of a standardized procedure and who had a bone marrow and serum tryptase assay on the same day. The diagnosis of systemic mastocytosis was established on the basis of the World Health Organization criteria as the gold standard. The accuracy of the bone marrow tryptase level in the diagnosis of systemic mastocytosis was assessed by a receiver operating characteristics curve analysis. The different sensitivity and specificity values, corresponding to the set of possible bone marrow tryptase level cut-off values, were estimated with 95% confidence intervals. RESULTS: Seventy-three patients were included. The diagnosis of systemic mastocytosis was established in 43 patients (58.9%). The median bone marrow tryptase level was 423 µg/L [95% CI: 217-868] in the systemic mastocytosis group and 7.5 µg/L [95% CI: 4.6-17.1] in the non-systemic mastocytosis group (P < 0.001). A cut-off value of 50 µg/L for bone marrow tryptase identified systemic mastocytosis with a sensitivity of 93.0% [95% CI: 80.9-98.5%] and a specificity of 90.0% [95% CI: 73.5-97.9%]. CONCLUSION AND CLINICAL RELEVANCE: The bone marrow tryptase level appears to be a valuable diagnostic criterion for confirming systemic mastocytosis. If this diagnosis can reliably be excluded by evaluation of the bone marrow tryptase level, there would be no need to perform a bone marrow biopsy.


Subject(s)
Bone Marrow/enzymology , Bone Marrow/pathology , Mastocytosis, Systemic/diagnosis , Mastocytosis, Systemic/enzymology , Tryptases/metabolism , Adolescent , Adult , Aged , Biomarkers , Biopsy , Female , Humans , Male , Middle Aged , ROC Curve , Reproducibility of Results , Tryptases/blood , Young Adult
6.
Rev Med Interne ; 36(4): 237-42, 2015 Apr.
Article in French | MEDLINE | ID: mdl-25554401

ABSTRACT

PURPOSE: Cryofibrinogenemia is an unknown disorder and studies dedicated to it are limited. The aim of our study was to report on the incidence, clinical manifestations and associated diseases in patients with isolated cryofibrinogenemia. METHODS: This is a retrospective single-center study. Patients included in this study had a positive and isolated detection of cryofibrinogen between January 1st, 2011 and December 31st, 2012. Identification was possible through the database of the laboratory of immunology. RESULTS: Two hundred and eighty-one consecutive orders of cryofibrinogenemia were identified. Seventy-three patients had a positive detection of cryofibrinogenemia. Among them, 12 had an isolated cryofibrinogenemia and sixty-one patients (84%) had concomitant cryofibrinogenemia and cryoglobulinemia. The mean age was 59±19years. Seven patients were female (58%). Cutaneous manifestations were present in half case. Peripheral nerve involvement was present in 5 cases (42%) and rheumatic manifestations in 4 patients (33%). A thrombotic event was reported in 7 patients (58%). Renal impairment was present in 7 patients. The median cryofibrinogen concentration was 254±304mg/L. Five patients had a secondary cryofibrinogenemia. The most often prescribed treatment was corticosteroids. CONCLUSION: Cryofibrinogenemia is an unknown disorder. Testing for cryoglobulinemia is more frequent than for cryofibrinogenemia whereas clinical manifestations are similar. Detection of cryofibrinogen is positive in most of the cases, with an important prevalence of thrombotic events in this population. This study confirms the importance of conducting prospective studies on cryofibrinogenemia.


Subject(s)
Cryoglobulinemia , Cryoglobulinemia/diagnosis , Female , France , Hospitals, University , Humans , Incidence , Male , Middle Aged , Retrospective Studies
7.
Am J Transplant ; 14(4): 867-75, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24580771

ABSTRACT

Although large retrospective studies have identified the presence of donor-specific antibodies (DSAs) to be a risk factor for rejection and impaired survival after liver transplantation, the long-term predicted pathogenic potential of individual DSAs after liver transplantation remains unclear. We investigated the incidence, prevalence and consequences of DSAs in maintenance liver transplant (LT) recipients. Two hundred sixty-seven LT recipients, who had undergone transplantation at least 6 months previously and had been screened for DSAs at least twice using single-antigen bead technology, were included and tested annually for the presence of DSAs. At a median of 51 months (min-max: 6-220) after an LT, 13% of patients had DSAs. At a median of 36.5 months (min-max: 2-45) after the first screening, 9% of patients have developed de novo DSAs. The sole predictive factor for the emergence of de novo DSAs was retransplantation (OR 3.75; 95% CI 1.28-11.05, p = 0.025). Five out of 21 patients with de novo DSAs (23.8%) developed an antibody-mediated rejection. Fibrosis score was higher among patients with DSAs. In conclusion, monitoring for the development of DSAs in maintenance LT patients is useful in case of graft dysfunction and to identify patients with a high risk of developing liver fibrosis.


Subject(s)
Graft Rejection/etiology , HLA Antigens/blood , Isoantibodies/blood , Liver Cirrhosis/etiology , Liver Diseases/surgery , Liver Transplantation/adverse effects , Adolescent , Adult , Aged , Female , Follow-Up Studies , Graft Rejection/epidemiology , Graft Rejection/mortality , Graft Survival , HLA Antigens/immunology , Humans , Incidence , Isoantibodies/immunology , Liver Cirrhosis/epidemiology , Liver Cirrhosis/mortality , Liver Diseases/complications , Liver Diseases/mortality , Male , Middle Aged , Prevalence , Prognosis , Prospective Studies , Reoperation , Retrospective Studies , Risk Factors , Survival Rate , Young Adult
8.
Immunogenetics ; 66(6): 353-60, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24676686

ABSTRACT

African green monkeys (AGM) are among the most widely used nonhuman primate models used in various fields of medical research. One species of AGM that originated from West Africa, Chlorocebus sabaeus, was introduced three centuries ago in the Caribbean islands. We present here a systematic study of the major histocompatibility complex (MHC) polymorphism of Caribbean AGM which is currently frequently used as an animal model. We studied 54 animals originated from Barbados (N=25) or Saint Kitts (N=29). The MHC polymorphism was characterized by means of 17 MHC microsatellites spread across MHC and DRB genotyping by DGGE sequencing. We defined nine frequent MHC haplotypes of which two were found in the two insular populations suggesting either past exchanges between the two populations or a common origin of the founders of the two populations. By the analysis of a previously described EST library, we characterized 38 MHC cDNA sequences (17 class I and 21 class II). In conclusion, we characterized for the first time the MHC polymorphism of Barbados and Saint Kitts AGM. We found a restricted polymorphism due to a founding effect, which is responsible for a strong bottleneck. The poorness of MHC polymorphism observed in the Caribbean AGM populations is similar to that observed in the Mauritian cynomolgus macaque population.


Subject(s)
Chlorocebus aethiops/genetics , Founder Effect , Major Histocompatibility Complex/genetics , Polymorphism, Genetic , Animals , Caribbean Region , Chlorocebus aethiops/immunology , Expressed Sequence Tags , Female , Genotyping Techniques , Haplotypes , Islands , Major Histocompatibility Complex/immunology , Male , Microsatellite Repeats/immunology , Sequence Analysis, DNA
9.
Immunogenetics ; 66(4): 219-30, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24569954

ABSTRACT

The cynomolgus macaque (Macaca fascicularis) is currently used as an animal model in various fields of immunology especially in the development of innovative vaccines for the prevention and treatment of infectious diseases. The polymorphism of the major histocompatibility complex (MHC) influences the development of adaptive immune responses and it is crucial to characterize the polymorphism of cynomolgus MHC genes. We present here a systematic study of the MHC class II haplotypes in the Filipino macaque population. By the study of a large sample of Filipino animals (N = 353), we have characterized 18 MHC class II haplotypes by means of genotyping seven microsatellites. The animals were DRB genotyped by means of PCR-SSO or DGGE-sequencing on genomic amplified fragments. We cloned and sequenced the complementary DNA (cDNA) of DQA, DQB, DPA, and DPB genes of 117 animals. Combining the microsatellite genotyping and cDNA characterized in the 117 animals, we defined genetic association between the cDNA and the microsatellites and characterized 18 MHC class II haplotypes. For 104 animals out of the 353 studied, the presence of a recombinant haplotype was highly probable. Thirty-four percent of recombination was located in 256 kb segment between D6S2876 and D6S2747 microsatellites, a region encompassing several hot spots of recombination in the human MHC.


Subject(s)
Genes, MHC Class II , Macaca fascicularis/genetics , Macaca fascicularis/immunology , Animals , DNA, Complementary/genetics , Gene Frequency , Genetic Association Studies/veterinary , Genetics, Population , Haplotypes , Humans , Microsatellite Repeats , Philippines , Polymorphism, Genetic , Recombination, Genetic , Species Specificity
11.
Tissue Antigens ; 81(1): 12-8, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23134469

ABSTRACT

The cynomolgus macaque (Macaca fascicularis) is a model of choice among primates for the study of local adaptation processes because of its mixed and wide insular and continental distribution. In a previous study, by using 12 markers [5 microsatellites located in the major histocompatibility complex (MHC) region and 7 outside MHC], we have detected a signal of positive selection on the microsatellite DRACA located inside the gene DRA. In order to refine the location of this signal of positive selection in the MHC region, we studied the genetic diversity of 36 markers (18 microsatellites spread across the MHC region and 18 autosomal microsatellites outside MHC) in a sample of 254 individuals from four populations (Vietnam, Java, the Philippines, and Mauritius). We estimated for each locus the deviation of F(st) from a neutral model by using two methods based on contrasted demographic models. The two approaches showed a signal of positive selection in the MHC class III region that is much more significant than the one previously reported for the marker DRACA which could have been influenced by a hitchhiking effect due to its proximity with the class III region.


Subject(s)
Macaca fascicularis/genetics , Major Histocompatibility Complex , Selection, Genetic , Animals , Genetic Markers , Genetic Variation , Genetics, Population , Linkage Disequilibrium , Microsatellite Repeats
12.
Am J Transplant ; 10(1): 89-98, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19656128

ABSTRACT

Rituximab off-label use includes organ transplantation. We review the occurrence of infectious disease and its outcome after rituximab therapy. Between April 2004 and August 2008, 77 kidney-transplant patients received rituximab therapy [2-8 courses (median 4) of 375 mg/m2 each] for various reasons. Their results were compared with a control group (n=902) who had received no rituximab. After a median follow-up of 16.5 (1-55) months for rituximab patients and 60.9 (1.25-142.7) months for control patients, the incidence of infectious disease was 45.45% and 53.9% (ns), respectively. The incidence of bacterial infection was similar between the two groups, whereas the viral-infection rate was significantly lower, and the rate of fungal infection was significantly higher in the rituximab group. Nine out of 77 patients (11.68%) died after rituximab therapy, of which seven deaths (9.09%) were related to an infectious disease, compared to 1.55% in the controls (p=0.0007). In the whole population, the independent predictive factors for infection-induced death were the combined use of rituximab and antithymocyte-globulin given for induction or anti-rejection therapy, recipient age, and bacterial and fungal infections. After kidney transplantation, the use of rituximab is associated with a high risk of infectious disease and death related to infectious disease.


Subject(s)
Antibodies, Monoclonal/adverse effects , Immunosuppressive Agents/adverse effects , Infections/etiology , Kidney Transplantation/adverse effects , Adult , Aged , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Murine-Derived , Bacterial Infections/etiology , Case-Control Studies , Female , Humans , Immunosuppressive Agents/therapeutic use , Infections/mortality , Male , Middle Aged , Mycoses/etiology , Risk Factors , Rituximab , Safety , Virus Diseases/etiology , Young Adult
13.
Neurology ; 72(15): 1301-9, 2009 Apr 14.
Article in English | MEDLINE | ID: mdl-19365051

ABSTRACT

OBJECTIVE: The literature on propriospinal myoclonus (PSM) is poor and there are no systematic reviews of the subject. We sought to clarify the spectrum of PSM. METHODS: We first prospectively investigated all patients seen in our movement disorders clinic with a firm diagnosis of PSM between 2002 and 2007. All had a standardized interview, detailed clinical examination, laboratory investigations, comprehensive neurophysiologic examination, and spinal cord MRI, including diffusion tensor imaging with fiber tracking (DTI-FT). We also collected drug responses. Finally, we conducted a systematic review of the literature. RESULTS: We enrolled 10 patients meeting the strict criteria for PSM, and also analyzed data on 50 patients from 26 previous reports. PSM occurred predominantly in male and middle-aged patients. The typical clinical picture consisted of myoclonic jerks consistently involving abdominal wall muscles, which worsen in the lying position. A premonitory sensation preceding the jerks and wake-sleep transition phase worsening were frequent. Most patients had a myoclonic generator at the thoracic level, with a myoclonus duration between 200 msec and 2 s. An underlying cause was infrequently found. DTI-FT detected cord abnormalities all of our patients. CONCLUSION: The clinico-physiologic spectrum of propriospinal myoclonus (PSM) is homogenous. Involvement of the abdominal wall muscles, worsening in the lying position, premonitory sensation, and wake-sleep transition phase worsening are helpful clinical clues. Diffusion tensor imaging with fiber tracking appears more sensitive than conventional MRI for detecting associated microstructural abnormalities of the spinal cord. Symptomatic treatment of PSM is not straightforward, and clonazepam is reported to be the most effective drug. Zonisamide may be an interesting option.


Subject(s)
Myoclonus/diagnosis , Myoclonus/therapy , Adolescent , Adult , Aged , Diffusion Magnetic Resonance Imaging , Electrodiagnosis , Electroencephalography , Electromyography , Evoked Potentials, Somatosensory/physiology , Female , Hematologic Tests , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Myoclonus/pathology , Neural Pathways/physiopathology , Prospective Studies , Spinal Cord/pathology , Spinal Cord/physiopathology , Tomography, X-Ray Computed , Young Adult
14.
Clin Nephrol ; 69(4): 239-43, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18397697

ABSTRACT

AIMS: To examine the prevalence of cryoglobulinemia (Cryo) and autoimmune markers in renal-transplant recipients in a stable condition, and to determine its risk factors and impact upon allograft function. PATIENTS AND METHODS: In May, 2006, 117 kidney-transplant (KT) recipients, aged 31 â 76 years, were tested for cryoglobulinemia, hepatitis B and C, complement C3, C4, CH50, antinuclear (ANAs), anticytoplasmic nuclear (ANCAs) and anticardiolipid antibodies, rheumatoid factor (RF), and lymphocyte subpopulations. Renal, liver, and hematological tests were also performed. Immunosuppressive regimens were based on calcineurin inhibitors (82%). RESULTS: Cryo was positive in 47 patients (Cryo(+): 40.2%), of whom 13 were HCV+ (27.7%), with characteristics of Type II in 21.2% and Type III in 78.8%. Cryo was positive in 13/16 (81.2%) of HCV+/RNA+ patients vs. 34/101 (33.6%, p = 0.0003) of HCV-negative patients. Cryo(+) RT patients had been recipients of a graft for longer (142 months) than Cryo(-) patients, i.e., 95 months (p = 0.02). Creatinine clearances were similar in the two groups (56 vs. 50 ml/mn, p = 0.5), as were microalbuminuria and albuminemia. There was no difference between Cryo(-) and Cryo(+) patients in terms of age, sex, HLA mismatch, daily steroid doses, liver and hematological tests, ANAs, anticardiolipid antibodies, serum complement, and lymphocyte subpopulations. RF occurred in all Cryo(+) patients and in 82.8% of Cryo(-) patients, with higher titers in the Cryo(+) group (23 vs. 9 UI/ml, p = 0.012). ANCA occurred in nine Cryo(-) but in no Cryo(+) patients (p = 0.013). Finally, a multivariate analysis was not able to determine any predictive factor associated with cryoglobulinemia. CONCLUSION: Cryoglobulinemia is frequent after KT, and is associated with HCV markers, RF, and absence of ANCA.


Subject(s)
Autoimmunity/immunology , Biomarkers/blood , Cryoglobulinemia/epidemiology , Kidney Transplantation/immunology , Adult , Aged , Cryoglobulinemia/diagnosis , Cryoglobulinemia/immunology , Cryoglobulins/analysis , Female , Hepatitis C/immunology , Humans , Male , Middle Aged , Prevalence , Rheumatoid Factor/blood
15.
Mol Ecol ; 17(4): 1009-19, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18261045

ABSTRACT

Cynomolgus macaques (Macaca fascicularis) were introduced on the island of Mauritius between 400 and 500 years ago and underwent a strong population expansion after a probable initial founding event. However, in practice, little is known of the geographical origin of the individuals that colonized the island, on how many individuals were introduced, and of whether the following demographic expansion erased any signal of this putative bottleneck. In this study, we asked whether the current nuclear genome of the Mauritius population retained a signature that would allow us to answer these questions. Altogether, 21 polymorphic autosomal and sex-linked microsatellites were surveyed from 81 unrelated Mauritius individuals and 173 individuals from putative geographical sources in Southeast Asia: Java, the Philippines islands and the Indochinese peninsula. We found that (i) the Mauritius population was closer to different populations depending on the markers we used, which suggests a possible mixed origin with Java playing most probably a major role; and (ii) the level of diversity was lower than the other populations but there was no clear and consistent bottleneck signal using either summary statistics or full-likelihood methods. However, summary statistics strongly suggest that Mauritius is not at mutation-drift equilibrium and favours an expansion rather than a bottleneck. This suggests that on a short time scale, population decline followed by growth can be difficult to deduce from genetic data based on mutation-drift theory. We then used a simple Bayesian rejection algorithm to estimate the number of founders under different demographic models (exponential, logistic and logistic with lag) and pure genetic drift. This new method uses current population size estimates and expected heterozygosity of Mauritius and source population(s). Our results indicate that a simple exponential growth is unlikely and that, under the logistic models, the population may have expanded from an initial effective number of individuals of 10-15. The data are also consistent with a logistic growth with different lag values, indicating that we cannot exclude past population fluctuation.


Subject(s)
Genetic Variation , Macaca fascicularis/genetics , Animals , Asia, Southeastern , Genotype , Mauritius , Microsatellite Repeats/genetics , Population Density
16.
Tissue Antigens ; 70(5): 398-411, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17854428

ABSTRACT

Across a large distribution range, population-specific factors as well as pathogen-mediated selection may shape species genetic diversity in the major histocompatibility complex (MHC). We have studied genetic diversity and population differentiation in the MHC region of the Southeast Asian cynomolgus macaque (Macaca fascicularis fascicularis), a species with large and discontinuous range, in order to investigate the role of demography vs selection. Genetic variation was assessed at seven MHC microsatellites on 272 individuals from five populations (Indochina, Java, Borneo, Philippines, and Mauritius). A high genetic diversity was observed in all populations and the Philippines but also the Mauritius populations were the most genetically differentiated. The strength and extent of linkage disequilibrium (LD) (up to 4 Mb) varies across populations mainly because of demographic factors. In Indochina, the complete lack of LD could be the signature of ancient hybridization between cynomolgus and rhesus macaques in the Indochinese peninsula. With the additional support of seven autosomal microsatellites, tests for outlier loci based on intrapopulation diversity and interpopulation differentiation (using F-statistic) allowed to dissociate demographic from selective histories: (i) demographic history may itself explain levels of MHC variability in the Mauritius populations and (ii) positive selection could be responsible for the Philippines population differentiation, especially in the MHC class II region. Among various pathogens, Plasmodium knowlesi and Plasmodium coatneyi are two likely candidates to explain the higher frequency of some MHC haplotypes. Indeed, literature describes low parasitemia in the Philippines individuals, contrasting with fatal infections provoked by these parasites in other cynomolgus macaque populations.


Subject(s)
Genetic Variation , Haplotypes , Linkage Disequilibrium , Macaca fascicularis/genetics , Major Histocompatibility Complex/genetics , Malaria/genetics , Animals , Asia, Southeastern , Genetics, Population , Humans , Macaca fascicularis/parasitology , Macaca mulatta , Malaria/epidemiology , Parasitemia/epidemiology , Parasitemia/genetics , Plasmodium knowlesi
17.
Immunogenetics ; 59(1): 17-23, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17146684

ABSTRACT

A new mutation of the CD40LG gene that encodes the CD40 ligand molecule was characterized in a young patient harboring a hyper-IgM with immunodeficiency syndrome. Inactivation of CD40LG gene resulted from the insertion of an AluYb8 element in exon 1 responsible for a total deficiency of CD40 ligand expression by T lymphocytes. Maternal transmission of the X-linked mutation was confirmed by gene-specific polymerase chain reaction. This is the 17th case report concerning a human genetic disease caused by an Alu element insertion in a coding sequence.


Subject(s)
Alu Elements/genetics , CD40 Ligand/genetics , Genetic Diseases, X-Linked/genetics , Hyper-IgM Immunodeficiency Syndrome, Type 1/genetics , Mutagenesis, Insertional/genetics , Base Sequence , Chromosomes, Human, X/genetics , Exons/genetics , Humans , Infant , Male , Molecular Sequence Data , Mutation
18.
Am J Transplant ; 6(6): 1285-96, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16686753

ABSTRACT

A nonhuman primate (NHP) study was designed to evaluate in nonlife-supporting kidney allografts the progression from acute rejection with transplant endarteritis (TXA) to chronic rejection (CR) with sclerosing vasculopathy. Group G1 (n = 6) received high cyclosporine A (CsA) immunosuppression and showed neither TXA nor CR during 90 days post-transplantation. Group G2 (n = 6) received suboptimal CsA immunosuppression and showed severe TXA with graft loss within 46 days (median). Arterial intimal changes included infiltration of macrophages and T lymphocytes (CD3, CD4, CD8) with few myofibroblasts, abundant fibronectin/collagen IV, scant collagens I/III, high rate of cellular proliferation and no C4d accumulation along peritubular capillaries. Group G3 (n = 12) received suboptimal CsA and anti-rejection therapy (rabbit ATG + methylprednisolone + CsA) of TXA. Animals developed CR and lost grafts within 65 days (median). As compared to G2, the arterial intimal changes showed less macrophages and T lymphocytes, an increased number of myofibroblasts, abundant fibronectin/collagen IV and scar collagens I/III, C4d deposition along capillaries in 60% of animals and transplant glomerulopathy in 80% of animals. In conclusion, CR is an immune stimulated process initiated during TXA with the accumulation and proliferation of myofibroblasts, and progressive deposition of collagens in the intima. Our experimental design appears well suited to study events leading to CR.


Subject(s)
Graft Rejection/immunology , Kidney Transplantation/immunology , Vascular Diseases/immunology , Acute Disease , Animals , Biomarkers/blood , Chronic Disease , Disease Models, Animal , Endarteritis/immunology , Endarteritis/pathology , Female , Kidney Transplantation/mortality , Kidney Transplantation/pathology , Macaca fascicularis , Male , Postoperative Period , Primates , Survival Analysis , Vascular Diseases/etiology
19.
Am J Primatol ; 67(3): 385-91, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16287102

ABSTRACT

Cross-amplification of 15 human microsatellites was performed successfully in cynomolgus (Macaca fascicularis) and rhesus (M. mulatta) macaques and 11 other Cercopithecidae species of biomedical and conservation relevance. To allow for quick, efficient, and high-throughput genotyping to assess intra- and interspecific genetic variation, we performed three multiplex sets, each comprised of five markers from different parts of the genome (i.e., autosomes, the MHC region, and the X-chromosome). These multiplex sets are likely to reveal allelic divergence between taxa, which could be used for their discrimination. Population studies on three regional populations of M. fascicularis and one of M. mulatta revealed that most of the loci, with the exception of one monomorphic locus, displayed polymorphisms (the expected heterozygosities were 0.48-0.91 for M. fascicularis, and 0.61-0.93 for M. mulatta), which makes them useful for population genetics. For the multiplex set M1, including the nonlinked autosomal markers, low probabilities of identity were observed: P(ID) values ranged from 8 x 10(-7) to 3 x 10(-5). This multiplex set is reliable for forensic applications, such as individual identification, parentage testing, and kinship analysis, in wild and captive populations.


Subject(s)
Animal Identification Systems/methods , Cercopithecidae/genetics , Microsatellite Repeats/genetics , Animals , Genetic Markers/genetics , Genetic Variation/genetics , Genotype , Species Specificity , Time Factors
20.
J Clin Virol ; 30(3): 218-23, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15135738

ABSTRACT

Screening for HIV infection can use many algorithms. When two different HIV antibody assays are used, discordant results may occur. To discriminate between HIV seroconversion, HIV variant infection and false positive reactivity, 30 consecutive subjects with two discordant HIV antibody-screening assays were extensively investigated for HIV infection. No subject had HIV seroconversion or reached HIV seropositivity criteria after a follow-up of 3 months. By contrast 36% became HIV negative by the use of both HIV screening assays. p24 Antigen, HIV-1 RNA, HIV-1 DNA, HIV-2 DNA assays and HIV isolation by sensitive culture were unable to identify HIV infection in the 30 subjects with discordant HIV screening assays. The data suggest that the use of two HIV screening assays increase false-positive HIV results without increasing clinical sensitivity. To compliment follow-up of HIV screening, early testing for HIV RNA could be useful to identify or eliminate a recent infection.


Subject(s)
HIV Antibodies/blood , HIV Infections/diagnosis , HIV-1/isolation & purification , HIV-2/isolation & purification , Adolescent , Adult , Aged , DNA, Viral/analysis , False Negative Reactions , Female , HIV Core Protein p24/analysis , HIV Infections/virology , HIV-1/classification , HIV-1/genetics , HIV-1/immunology , HIV-2/classification , HIV-2/genetics , HIV-2/immunology , Humans , Male , Middle Aged , RNA, Viral/analysis , Virus Cultivation
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