5 research outputs found

    E.U. paediatric MOG consortium consensus: Part 3 – Biomarkers of paediatric myelin oligodendrocyte glycoprotein antibody-associated disorders

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    A first episode of acquired demyelinating disorder (ADS) in children is a diagnostic challenge as different diseases can express similar clinical features. Recently, antibodies against myelin oligodendrocyte glycoprotein (MOG) have emerged as a new ADS biomarker, which clearly allow the identification of monophasic and relapsing ADS forms different from MS predominantly in children. Due to the novelty of this antibody there are still challenges and controversies about its pathogenicity and best technique to detect it. In this manuscript we will discuss the recommendations and caveats on MOG antibody assays, role in the pathogenesis, and additionally discuss the usefulness of other potential new biomarkers in MOG-antibody associated disorders (MOGAD)

    Regulatory T Cells Increase After rh-MOG Stimulation in Non-Relapsing but Decrease in Relapsing MOG Antibody-Associated Disease at Onset in Children

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    International audienceMOGAD. Increase of Th17 cells was significant in MOGNR (means: 0.63 ± 0.15 vs. 1.36 ± 0.43; Wilcoxon-test p = 0.03) but not in MOGR. CD4 + T regs were significantly increased in MOGNR (means: 3.51 ± 0.7 vs. 4.59 ± 1.33; Wilcoxon-test p = 0.046) while they decreased in MOGR. CD45RA-Foxp3 + T regs were significantly decreased in MOGR (means: 2.37 ± 0.23 vs. 1.99 ± 0.17; paired t-test p = 0.021), but not in MOGNR. MOGR showed the highest ratio of effector T regs /non suppressive-T regs, which was significantly higher than in MOGNR. Conclusions: Our findings suggest that CD4 + Th2 and Th17 cells are involved in the pathophysiology of MOGAD in children. The opposite response of T regs to rh-MOG in MOGNR, where CD4 + T regs increased, and in MOGR, where CD45RA-Foxp3 + T regs decreased, suggests a probable loss of tolerance toward MOG autoantigen in MOGR which may explain relapses in this recurrent pediatric autoimmune disease

    Simple FISH-based evaluation of spermatic nuclear architecture shows an abnormal chromosomal organization in balanced chromosomal rearrangement carriers

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    International audienceIntroduction: Interphasic DNA has a constant three-dimensional conformation, which is particularly striking for spermatic DNA, with distinct chromosomal territories and a constant chromosomal conformation. We hypothesized that this organization is fragile, and that an excess or a lack of chromosomal segments could hinder the genomic structure as a whole.Methods: Five human male chromosomal translocation carriers and five controls were included. Spermatic DNA spatial organization was studied, in both balanced and unbalanced spermatozoa, with two-dimensional fluorescent in situ hybridization (FISH) via analysis of chromosomes not implicated in the cases' translocations, compared to that of normal controls. Two parameters were studied: the distance between the two telomeric ends of chromosome 1, and the area of the chromosomal territories of chromosomes 1 and 17.Results: Sperm FISH analysis of rearrangement carriers revealed changes in the nuclear architecture compared to that of controls. Inter-telomeric distance and chromosomal territories areas were both significantly increased.Discussion: We show that an excess or lack of chromosomal segments can hinder the normal spatial nuclear architecture in sperm. These results show that nuclear architecture is a fragile assembly, and that local chromosomal abnormalities may impact the nucleus as a whole. This suggests a potential avenue for selection of spermatozoa prior to in vitro fertilization, not only in rearrangement carriers but also in the infertile population at large. Furthermore, we suggest that 2D-FISH could possibly be a useful tool in assessing spermatic nuclear organization in a way to evaluate male fertility

    Double chromosomal translocation in an infertile man: one-step FISH meiotic segregation analysis and reproductive prognosis

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    International audienceBackground: The prevalence of chromosomal translocations is 1/500 in the general population. While in the vast majority of cases, carriers have a normal phenotype; they can present with difficulty conceiving due to the presence of a proportion of unbalanced gametes as a consequence of abnormal chromosomal segregation during meiosis. Since complex translocations involve three or more chromosomes, meiotic segregation leads to a greater number of possible combinations which effectively complicate both their study and therapeutic care.Case presentation: We report on the case of a male carrier of a complex homogeneous double Robertsonian translocation: 44, XY, der(13;14)(q10;q10),der(21;22)(q10;q10). We studied his meiotic segregation by FISH on spermatozoa from the initial sample, as well as following discontinuous gradient centrifugation and after incubation in an hypo-osmotic solution.Conclusion: We report a method to study in a simple single-step manner the meiotic segregation of double Robertsonian translocations in spermatozoa. Further, our results suggest that reproductive prognosis of affected individuals may be markedly improved by HOST-based sperm selection (HBSS)

    Association of Maternal First Trimester Serum Levels of Free Beta Human Chorionic Gonadotropin and Hypospadias: A Population Based Study

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    Purpose:Human chorionic gonadotropin stimulates fetal testosterone production and contributes to normal development of male genitalia. Using population based data we hypothesized that differences in maternal free beta human chorionic gonadotropin may be associated with hypospadias.Materials and Methods:Data were obtained from the Paris Registry of Congenital Malformations (REMAPAR) (2011 to 2016). The initial study population included 3,172 pregnant women who gave birth to a singleton live born male infant with a congenital malformation. After exclusion of cases with unknown beta human chorionic gonadotropin and those with chromosomal or genetic abnormalities, the study population included 194 boys with isolated hypospadias and 1,075 controls. For cases with operative notes (125) we obtained data on type (proximal/distal) of hypospadias. Using quantile regression we compared median values of multiple of median beta human chorionic gonadotropin measured for first trimester Down syndrome screening (10th to 13th gestational weeks) for overall as well as by type of hypospadias vs controls. We also considered possible effects of placental dysfunction (maternal age, intrauterine growth retardation and preterm births) as potential confounding factors.Results:Overall the median beta human chorionic gonadotropin multiple of median was comparable for women who had an infant with hypospadias vs controls (0.99 vs 0.95, p=0.3). However, proximal hypospadias was associated with a statistically significant higher median multiple of median than distal hypospadias or unspecified (1.49 vs 0.92 vs 1.05, p=0.02). The estimates were comparable after adjustment for placental dysfunction.Conclusions:Our findings support the hypothesis that an alteration in maternal beta human chorionic gonadotropin levels is associated with hypospadias. However, this association appears to be limited to proximal hypospadias
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