Immune phenotype predicts new onset diabetes after kidney transplantation

Few data are available concerning immune factors involved in the occurrence of new onset diabetes after transplantation (NODAT). Our objective was to determine an immune profile associated with the subsequent development of NODAT. The secondary objective was to build a predictive model of NODAT. We studied a prospective cohort of incident kidney transplant patients to determine whether pre-transplant immune characteristics could be associated with the occurrence of NODAT. 818 patients were included. We observed a significant inverse correlation between BMI and recent thymic emigrants (RTE) % at transplant time (p < 0.001). 177 (17.3%) of 677 non-diabetic patients experienced NODAT in the first year post-transplant. In multivariate analysis, age, body mass index (BMI), use of Tacrolimus, use of anti-thymocyte globulins (ATG), higher B cell count, and lower recent thymic emigrants (RTE) % were associated with NODAT. A differential effect of immune profile was observed in ATG-treated patients and non-ATG-treated patients. B cell count predicts NODAT only in non-ATG-treated patients whereas lower RTE% was associated with NODAT only in ATG-treated patients. Tacrolimus sparing and B cell depletion may efficiently prevent NODAT in selected patients. We identified an immune profile associated with the occurrence of post-transplant diabetes. Further studies should better precise the exact mechanisms involved in this association. Trial registration NCT02843867, registered July 8, 2016 – retrospectively registered https://clinicaltrials.gov/ct2/show/record/NCT02843867.     

Human pegivirus isolates characterized by deep sequencing from hepatitis C virus-RNA and human immunodeficiency virus-RNA–positive blood donations,France

Human pegivirus (HPgV, formerly GBV-C) is a member of the genus Pegivirus, family Flaviviridae. Despite its identification more than 20 years ago, both natural history and distribution of this viral group in human hosts remain under exploration. Analysis of HPgV genomes characterized up to now points out the scarcity of French pegivirus sequences in databases. To bring new data regarding HPgV genomic diversity, we investigated 16 French isolates obtained from hepatitis C virus-RNA and human immunodeficiency virus-RNA–positive blood donations following deep sequencing and coupled molecular protocols. Initial phylogenetic analysis of 5′-untranslated region (5′-UTR)/E2 partial sequences permitted to assign HPgV isolates to genotypes 2 (n = 15) and 1 (n = 1), with up to 16% genetic diversity observed for both regions considered. Seven nearly full-length representative genomes were characterized subsequently, with complete polyprotein coding sequences exhibiting up to 13% genetic diversity; closest nucleotide (nt) divergence with available HPgV sequences was in the range 7% to 11%. A 36 nts deletion located on the NS4B coding region (N-terminal part, 12 amino acids) of the genotype 1 HPgV genome characterized was identified, along with single nucleotide deletions in two genotype 2, 5′-UTR sequences.     

Isolation of Francisella tularensis by Centrifugation of Shell Vial Cell Culture from an Inoculation Eschar

A 52-year-old man was admitted to the hospital following the development of an inoculation eschar and fever six days after being bitten by a tick. He was clinically diagnosed as suffering from rickettsiosis. Eschar biopsy cultures on standard bacteriological media remained sterile. However, inoculation of cells with the homogenized specimen by the centrifugation-shell vial technique (M. Marrero and D. Raoult, Am. J. Trop. Med. Hyg. 40:197–199, 1989) resulted in the recovery of a bacterium. Determination of the sequence of the 16S rRNA gene amplified from the organism and comparison of the sequence to other sequences identified it as a strain of Francisella tularensis, whereas the specific serology was still negative. Our findings demonstrate that the centrifugation-cell culture, which is a tool for investigation of tick-transmitted diseases, may have the potential to serve as a method for the cultural isolation of F. tularensis.     

Coxiella burnetii Induces Reorganization of the Actin Cytoskeleton in Human Monocytes

Coxiella burnetii, an obligate intracellular bacterium which survives in myeloid cells, causes Q fever in humans. We previously demonstrated that virulent C. burnetii organisms are poorly internalized by monocytes compared to avirulent variants. We hypothesized that a differential mobilization of the actin cytoskeleton may account for this distinct phagocytic behavior. Scanning electron microscopy demonstrated that virulent C. burnetii stimulated profound and polymorphic changes in the morphology of THP-1 monocytes, consisting of membrane protrusions and polarized projections. These changes were transient, requiring 5 min to reach their maximum extent and vanishing after 60 min of incubation. In contrast, avirulent variants of C. burnetii did not induce any significant changes in cell morphology. The distribution of filamentous actin (F-actin) was then studied with a specific probe, bodipy phallacidin. Virulent C. burnetii induced a profound and transient reorganization of F-actin, accompanied by an increase in the F-actin content of THP-1 cells. F-actin was colocalized with myosin in cell protrusions, suggesting that actin polymerization and the tension of actin-myosin filaments play a role in C. burnetii-induced morphological changes. In addition, contact between the cell and the bacterium seems to be necessary to induce cytoskeleton reorganization. Bacterial supernatants did not stimulate actin remodeling, and virulent C. burnetii organisms were found in close apposition with F-actin protrusions. The manipulation of the actin cytoskeleton by C. burnetii may therefore play a critical role in the internalization strategy of this bacterium.     

Subclinical speckled perifollicular melanosis of the scalp

Based on the clinical presentation of some skin pigmentation disorders it is thought that a bicompartmental functional system exists in the epidermal melanocyte population. It corresponds to the perifollicular and interfollicular compartments, respectively. The present study was undertaken looking for the presence of such a system on scalp unaffected by pigmentary disorders. The scalps of 100 men with incipient to severe androgenic alopecia were examined using a videocamera equipped with an internal ultraviolet light-emitting unit. The face, trunk and limbs were similarly examined in 45 of these adults and in 13 children of both sexes. In 92 men, a subclinical hypermelanosis was found as a speckled pattern centered on every single follicle. With increasing baldness severity, another epidermal hyperpigmentation pattern involving the interfollicular area was superimposed to the perifollicular pattern. These stereotyped patterns of subclinical melanoderma were also disclosed on the face of adults, but not in children. In addition, the spotty perifollicular pattern was discrete or not apparent on the other parts of the body. It is concluded that the perifollicular subclinical melanotic pattern is a regional characteristic of cephalic skin, perhaps related to the local production of melanocortins, particularly alpha-MSH by the pilosebaceous unit.     

Traditional and molecular techniques for the study of emerging bacterial diseases: one laboratory's perspective

Identification of emerging bacterial pathogens generally results from a chain of events involving microscopy, serology, molecular tools, and culture. Because of the spectacular molecular techniques developed in the last decades, some authors think that these techniques will shortly supplant culture. The key steps that led to the discovery of emerging bacteria have been reviewed to determine the real contribution of each technique. Historically, microscopy has played a major role. Serology provided indirect evidence for causality. Isolation and culture were crucial, as all emerging bacteria have been grown on artificial media or cell lines or at least propagated in animals. With the use of broad-range polymerase chain reaction, some bacteria have been identified or detected in new clinical syndromes. Culture has irreplaceable advantages for studying emerging bacterial diseases, as it allows antigenic studies, antibiotic susceptibility testing, experimental models, and genetic studies to be carried out, and remains the ultimate goal of pathogen identification.     

Genetics and epidemiology of Wilms' tumor: The French Wilms' tumor study

A complete family history was obtained for 501 patients with Wilms' tumor, treated in departments of pediatric oncology in whole France. The information was collected by self-questionnaire and/or by interview of parents. The proportion of bilateral cases is 4.6% and there are 12 patients (2.4%) with a positive family history of Wilms' tumor. The affected relatives are most often distant and no first degree relative was affected. Apart from the well-known associations with aniridia, hemihypertrophy, genitourinary anomalies, Beckwith-Wiedeemann, and Drash syndromes, there is also a significant excess of congenital heart defects (P = .008) which remains to be explained. Several findings support the bimutational hypothesis such as earlier diagnosis and increased parental age in bilateral cases. No particular anomalies and no increased frequency of childhood cancer were found in patients' relatives. The frequency of Wilms' tumor in relatives was estimated to be less than 0.4% in sibs, 0.06% in unclesand aunts, and 0.04% in first cousins. These figures are very different from those found in retinoblastoma and suggest that the mechanism may be more complex in Wilms' tumor. This conclusion is in agreement with molecular biology studies in tumors and linkage analysis in multiple case families which suggest that more than one locus is involved. © 1992 Wiley-Liss, Inc.     

Large geodes in rheumatoid arthritis without joint destruction

Although subchondral geodes are a well-known radiological feature of rheumatoid arthritis (RA), large geodes are uncommon. Progressive bone damage with pathological fractures has been reported. We report the case of a 49-year-old man with seropositive RA in whom large, rapidly progressive geodes in the wrists, hands, and feet contrasted with the absence of joint destruction, good functional tolerance, and moderate abnormalities of markers for inflammation. The location and rapid progression of the cyst-like lesions in this patient were highly unusual.