Association of paediatric autoimmune cytopenia and inflammatory bowel disease suggests a common genetic origin.

The association of autoimmune cytopenia (AIC) and inflammatory bowel disease (IBD) has been reported in small series, but the incidence of and risk factors for IBD in children with AIC are not known. One thousand six hundred nine children with chronic immune thrombocytopenic purpura, autoimmune haemolytic anaemia or Evans syndrome from the prospective OBS'CEREVANCE cohort are included in this study. Overall, 15 children were diagnosed with IBD, including 14 who developed IBD after AIC diagnosis (median delay: 21 months). The only risk factor for IBD development is age at AIC over 10 years. Out of 10 children genetically tested, germline variants associated with autoimmune disorders were identified in three (CTLA4: two, DOCK11: one). In children and adolescents monitored for AIC or past history of AIC, especially children over 10 years, gastro-intestinal (GI) symptoms (recurrent abdominal pains, GI bleeding, chronic diarrhoea, weight loss) should suggest IBD and deserve specific work-up and genetic studies. Identification of a causal germline variant will allow targeted therapy.

Dynamics of heterogeneous wetting in periodic hybrid nanopores.

We present experimental and theoretical results concerning the forced filling and spontaneous drying of hydrophobic cylindrical mesopores in the dynamical regime. Pores are structured with organic/inorganic moieties responsible for a periodicity of the surface energy along their axis. We find that the forced intrusion of water in these hydrophobic pores presents a slow dynamics: the intrusion pressure decreases as the logarithm of the intrusion time. We find that this slow dynamics is well described quantitatively by a classical model of activated wetting at the nanoscale, giving access to the structural length scales and surface energies of the mesoporous material.

Effects of a dietary supplement enriched in palmitoleic acid on fatty acid composition of follicular fluid, granulosa cell metabolism, and oocyte developmental capacity in early lactation dairy cows.

In high-yielding dairy cows, some fertility traits can be influenced by the fatty acid (FA) composition of the follicular fluid during early lactation. The first objective of the current study was to evaluate the potential of dietary supplements enriched in specific FA to influence the FA composition of follicular fluid lipid classes in early lactation dairy cows. The second objective was to determine the influence of the resulting follicular fluid FA composition on the folliculogenesis, lipid and energy metabolism of granulosa cells, as well as oocyte quality and embryo development. Twenty Holstein multiparous cows in late gestation were randomly assigned to 200 g/d of FA supplements enriched in (1) palmitic acid (control treatment; 82% 16:0; PA) in the rumen or (2) palmitoleic acid (sea buckthorn oil; 27% cis-9 16:1, 28% 16:0, 22% cis-9 18:1, and 11% cis-9,cis-12 18:2; SBT) in the abomasum. The treatment period ranged from 20 ± 5 d precalving to 67 ± 2 d postcalving. Cumulus-oocyte complexes, granulosa cells, and follicular fluid were recovered from 2 sequential sessions of ovum pick-up (OPU-1 and OPU-2) at 46 and 67 ± 2 d postcalving (mean ± standard deviation). On the same days, blood samples were collected. Milk performance was recorded, and feed and milk samples were collected from d 8 to 10 ± 3 (onset of lactation), d 35 to 37 ± 2 (before OPU-1), and d 63 to 65 ± 2 (before OPU-2). Treatments did not affect milk yield or fat concentration throughout the experimental trial. Compared with PA, SBT increased the cis-9 16:1 concentration in milk fat, in plasma esterified lipid classes (phospholipids, cholesterol esters, and triacylglycerols), and in follicular fluid phospholipids and cholesterol esters at OPU-1. Abundance of mRNA for stearoyl-CoA desaturase 1 and 5, and perilipin 2 in granulosa cells was not different between treatments, but an increase in the level of stearoyl-CoA desaturase 5 was observed between the 2 OPU periods. Treatments did not affect oocyte quality and developmental capacity or embryo lipid metabolism when cultivated in vitro. These results suggest that limited modifications in the FA composition of the oocyte microenvironment via dietary lipid supplements enriched in specific FA had no major effects on granulosa cell metabolism and oocyte developmental capacity in early lactation cows.

Evaluation of timolol maleate gel for management of hard-to-heal chronic venous leg ulcers. Phase II randomised-controlled study.

BACKGROUND: Venous leg ulcers (VLUs) often take a very long time to heal. Timolol maleate has been reported as displaying efficacy in healing of VLUs. OBJECTIVES: To evaluate the efficacy of timolol maleate gel in the management of hard-to-heal VLUs and to assess its safety as a topical agent during 12 weeks of use in combination with conventional treatment. METHODS: A prospective, phase-II randomised-controlled trial with a sample size based on Fleming's one-stage design (P0=0.25, P1=0.45, alpha=0.1, beta=0.2) was planned. Patients with VLUs present for ≥24 weeks and with ≥50% granulation tissue were included. One drop of sustained-release timolol gel (Timoptol® LP 0.5%, Santen, Tampere, Finland) per 6 cm2 VLU area was applied every 2 days for 12 weeks in timolol-treated patients, as adjuvant therapy to the standard care protocol (interface dressing and multilayer venous compression). Controls received standard care alone. The primary endpoint was to obtain ≥40% reduction in ulcer area at week 12 (W12). RESULTS: Forty-three patients were randomised to the study, with 40 receiving at least one treatment and included in the analysis: 21 timolol-treated patients and 19 controls (females: 70%; median age: 72.5 [range 35-93] years). At W12, ≥40% ulcer-area reduction was achieved in 14/21 (67%) timolol-treated patients vs. 6/19 (32%) controls. No serious adverse events occurred. Local wound infections not requiring systemic antibiotics occurred in 5 cases in the timolol group and in one case in the controls. CONCLUSIONS: These results support the benefit and safety of using timolol maleate to manage hard-to-heal VLUs, but confirmation is required in a larger multicentre randomised phase-III study.

Genetic and phenotypic consequences of early domestication in black soldier flies (Hermetia illucens).

The black soldier fly, Hermetia illucens, is an emerging biotechnological agent with its larvae being effective converters of organic waste into usable bio-products including protein and lipids. To date, most operations use unimproved commercial populations produced by mass rearing, without cognisance of specific breeding strategies. The genetic and phenotypic consequences of these commercial practices remain unknown and could have a significant impact on long-term population viability and productivity. The aim of this study was thus to assess the genetic and phenotypic changes during the early phases of colony establishment and domestication in the black soldier fly. An experimental colony was established from wild founder flies and a new microsatellite marker panel was developed to assess population genetic parameters along with the phenotypic characteristics of each generational cohort under captive breeding. The experimental colony was characterised by a small effective population size, subsequent loss of genetic diversity and rapid genetic and phenotypic differentiation between the generational cohorts. Ultimately, the population collapsed by the fifth generation, most likely owing to the adverse effect of inbreeding depression following the fixation of deleterious alleles. Species with r-selected life history characteristics (e.g. short life-span, high fecundity and low larval survival) are known to pose particular challenges for genetic management. The current study suggests that sufficient genetic and phenotypic variations exist in the wild population and that domestication and strain development could be achieved with careful population augmentation and selection during the early stages of colony establishment.

Management of granulomatous foreign body reaction to fillers with methotrexate.

BACKGROUND: Granulomatous foreign body reactions (GFBR) have been reported after injection with almost every soft tissue fillers, more commonly with non-biodegradable ones. Such granulomatosis is rare but can cause significant discomfort owing to their aesthetic and functional repercussions. OBJECTIVE: To determine whether immunomodulation with low doses of methotrexate is effective in the treatment of GFBR to filler material. METHODS: Clinical case series of four patients with severe, treatment-resistant GFBR to non-biodegradable fillers in the Department of Dermatology of Bordeaux University Hospital, Bordeaux, France, successfully treated with oral or subcutaneous methotrexate, 10-15 mg weekly during 6 months. Adverse events were monitored throughout the treatment once weekly the first month then once monthly the remaining 5 months. RESULTS: Four women with a mean age of 73.7 years (66-85 years) and nodularity of the face were included and treated up to 6 months. Histological findings were consistent with GFBR to liquid injectable silicone in 2 cases, polymethylmethacrylate in 1 case and hydroxyethylmethacrylate in the last case. The delay after injection of the filler material was from 17 to 30 years. In one patient, inflammatory lesions followed dental care. After 6 months of treatment with 10-15 mg once weekly, all patients were cleared. Three patients developed a mild hepatic cytolysis (grade 1 or 2). Methotrexate could be maintained in those 3 cases and was discontinuated after 6 months in all cases. Two patients developed recurrence of lesions, 28 and 9 months, respectively, after treatment stops, requiring reintroduction of treatment. The two other patients remained cleared after 6 months of follow-up. CONCLUSION: Low doses of methotrexate appear to offer a low-risk therapeutic alternative in resistant and severe GFBR to fillers. A prospective study with long-term follow-up is required to confirm these preliminary observations.

Sensory perception of textural properties of cosmetic Pickering emulsions.

OBJECTIVE: The increasing interest for the Pickering emulsions is based on the possibility to replace classical emulsifiers by the solid particles. This approach is extremely attractive for the cosmetic field. But, the main difficulty is to obtain stable emulsions with appreciable skin feel. However, there is no information about the texture of such systems. The aim of this study is to formulate and describe the textural properties of cosmetic Pickering emulsions compared with conventional systems. METHODS: Three metal oxides were selected: titanium dioxide, zinc oxide and silicon dioxide, able to form stable and totally emulsified systems. A conventional emulsifier was used to formulate the emulsion of reference. Finally, the mixture of two emulsifying systems, combining both, surfactant and particles, was also studied. Then, a sensory panel was asked to quantify the intensities of the perception of the seven discriminating attributes. RESULTS: Each particle brought its properties to the textural perception of the emulsion. TiO2 particles ensured the whitening effect of the emulsions, SiO2 provided the screech residue, whereas ZnO gave intermediate results. The conventional surfactant was perceived as glossy, greasy and more difficult to spread. The particle/surfactant mixtures gave mostly in-between results. CONCLUSIONS: The study shows that the sensory profile of Pickering emulsions is indirectly and directly governed by the particle properties used for the emulsion stabilization: indirectly, through affecting the emulsion orientation (oil in water or water in oil), the droplet organization and viscosity, and directly, through the particle perception on the skin surface.

OBJECTIF: L'intérêt croissant pour les émulsions de type Pickering repose sur la possibilité de remplacer les émulsifiants classiques par les particules solides. Cette approche est extrêmement attractive pour le domaine cosmétique. Mais, la principale difficulté est d'obtenir des émulsions stables avec un toucher agréable. Cependant, il n'y a aucune information sur la texture de tels systèmes. Le but de cette étude est de formuler et de décrire les propriétés de texture des émulsions cosmétiques de type Pickering par rapport aux systèmes conventionnels. MÉTHODES: Trois oxydes métalliques ont été sélectionnés: le dioxyde de titane, l'oxyde de zinc et le dioxyde de silicium, capables de former des systèmes stables et totalement émulsifiés. Un émulsifiant conventionnel a été utilisé pour formuler l'émulsion référence. Enfin, le mélange de deux systèmes émulsionnants, combinant à la fois le tensioactif et les particules, a également été étudié. Ensuite, un panel sensoriel a quantifié les intensités de perception des sept attributs discriminants. RÉSULTATS: Chaque particule a apporté ses propriétés à la perception de la texture de l'émulsion. Les particules de TiO2 ont assuré l'effet blanchissant des émulsions, SiO2 a rendu le résidu crissant, tandis que ZnO a donné des résultats intermédiaires. Le surfactant conventionnel était perçu comme brillant, gras et plus difficile à étaler. Les mélanges particules/tensioactifs ont donné principalement des résultats intermédiaires. CONCLUSION: L'étude montre que le profil sensoriel des émulsions Pickering est indirectement et directement gouverné par les propriétés des particules utilisées pour la stabilisation de l'émulsion: indirectement, en contrôlant l'orientation de l'émulsion (huile dans l'eau ou eau dans l'huile), l'organisation des gouttelettes et la viscosité, et directement, grâce à la perception des particules à la surface de la peau.

[Ichtyosiform erythroderma revealing a severe combined immunodeficiency]. / Érythrodermie ichtyosiforme révélant un déficit immunitaire combiné sévère.

BACKGROUND: Severe combined immunodeficiency (SCID) is a the most severe form of primary immunodeficiency and is highly heterogeneous. We report an atypical form of SCID revealed by exfoliative erythroderma. PATIENTS AND METHODS: A 3-month-old boy, born to consanguineous parents, was admitted to the dermatology department with exfoliative erythroderma associated with eczematous patches and alopecia of the scalp, eyelashes, and eyebrows, but with no lymphadenopathy or hepatosplenomegaly. He displayed chronic diarrhea and recurrent infection since birth. A complete blood count showed marked leukocytosis with eosinophilia and lymphocytosis. These clinical and biological findings improved partly with topical steroids. The patient no longer had erythroderma and showed regrowth of hair, eyelashes and eyebrows. The subsequent CBC showed less marked eosinophilia with mild lymphopenia and no leukocytosis. Immunoglobulin levels were undetectable. Primary immunodeficiency was discussed. Immunological investigations concluded on a diagnosis of T-B-NK+ SCID. Mutation analysis revealed a homozygous c.1338C>G (pCys446Trp) mutation in the RAG2 gene. Hematopoietic stem cell transplantation is planned in the near future. CONCLUSION: This case illustrates atypical T-B-NK+ SCID revealed by severe exfoliative erythroderma in a 3-month-old boy with RAG2 gene mutation. Neonatal erythroderma must be considered a warning sign of primary immunodeficiency requiring immediate immunological phenotyping as well as genetic testing for a definitive diagnosis.

Cutaneous granulomas with primary immunodeficiency in children: a report of 17 new patients and a review of the literature.

BACKGROUND: Paediatric cutaneous granuloma with primary immunodeficiency (PID) is a rare condition. The physiopathology is unclear, and treatment is challenging. We report on 17 paediatric cases and review the literature. OBJECTIVES: To make dermatologists and dermatopathologists aware of the diagnostic value of skin granulomas in paediatric PID. METHODS: We collected data on 17 patients with cutaneous granulomas and PID registered with us and also reviewed 33 cases from the literature. RESULTS: Cutaneous granuloma was the presenting feature of the PID in 15 of the 50 collated cases. The lesions presented as red-brownish nodules and infiltrated ulcerative plaques, predominantly on the face and limbs. Scleroderma-like infiltration on a single limb was observed in 10% of the cases. The associated PID was ataxia-telangiectasia (52%), combined immunodeficiency (24%), cartilage-hair hypoplasia (6%) and other subtypes (18%). The granulomas were mostly sarcoidal, tuberculoid, palisaded or undefined subtypes. In some patients, several different histopathologic granulomatous patterns were found in the same biopsy. Some granulomas were associated with the presence of a vaccine strain of rubella virus. CONCLUSION: Cutaneous granulomas associated with a PID have a variable clinical presentation. A PID can be suspected when crusty, brownish lesions are found on the face or limbs. The concomitant presence of several histological subtypes in a single patient is suggestive of a PID.

[Ensuring safety of patients under antipsychotic drugs: Impact of medical and pharmaceutical collaboration at prison]. / Sécurisation de la prise en charge médicamenteuse des patients sous antipsychotiques : impact de la collaboration médico-pharmaceutique à la Maison d'Arrêt de Lyon-Corbas.

OBJECTIVE: Antipsychotics are the standard treatment for psychosis. However, when combined with other lifestyle factors they are partially responsible for an excessive mortality rate. A clinical and paraclinical monitoring of patients is therefore necessary. In 2011, this element led doctors and pharmacists to improve monitoring and formalize a follow-up adapted to inmate patients. The aim of this study was to assess the impact of medical-pharmaceutical collaboration on monitoring quality of patients treated by antipsychotics. METHODS: This is a retrospective study including all patients treated by antipsychotics for at least 6 months in 2011 and again in 2015. Data were collected from medical files. The indicator assessing the monitoring quality was the compliance percentage, of registred parameters for each patient on the basis of specific guidelines. RESULTS: In 2015 compared to 2011, the monitoring quality increased for 9 out of 10 parameters. This improvement was statisticaly significant for 7 of them : Body Mass Index, lipid test, complete blood count, transaminase, ionogram, glycemia, glomerular filtration rate. CONCLUSION: The actions of improvement collectivelly implemented in 2011 had a concrete impact on patients in the follow-up in 2015.

Quality control implementation for universal characterization of DNA and RNA viruses in clinical respiratory samples using single metagenomic next-generation sequencing workflow.

BACKGROUND: In recent years, metagenomic Next-Generation Sequencing (mNGS) has increasingly been used for an accurate assumption-free virological diagnosis. However, the systematic workflow evaluation on clinical respiratory samples and implementation of quality controls (QCs) is still lacking. METHODS: A total of 3 QCs were implemented and processed through the whole mNGS workflow: a no-template-control to evaluate contamination issues during the process; an internal and an external QC to check the integrity of the reagents, equipment, the presence of inhibitors, and to allow the validation of results for each sample. The workflow was then evaluated on 37 clinical respiratory samples from patients with acute respiratory infections previously tested for a broad panel of viruses using semi-quantitative real-time PCR assays (28 positive samples including 6 multiple viral infections; 9 negative samples). Selected specimens included nasopharyngeal swabs (n = 20), aspirates (n = 10), or sputums (n = 7). RESULTS: The optimal spiking level of the internal QC was first determined in order to be sufficiently detected without overconsumption of sequencing reads. According to QC validation criteria, mNGS results were validated for 34/37 selected samples. For valid samples, viral genotypes were accurately determined for 36/36 viruses detected with PCR (viral genome coverage ranged from 0.6 to 100%, median = 67.7%). This mNGS workflow allowed the detection of DNA and RNA viruses up to a semi-quantitative PCR Ct value of 36. The six multiple viral infections involving 2 to 4 viruses were also fully characterized. A strong correlation between results of mNGS and real-time PCR was obtained for each type of viral genome (R2 ranged from 0.72 for linear single-stranded (ss) RNA viruses to 0.98 for linear ssDNA viruses). CONCLUSIONS: Although the potential of mNGS technology is very promising, further evaluation studies are urgently needed for its routine clinical use within a reasonable timeframe. The approach described herein is crucial to bring standardization and to ensure the quality of the generated sequences in clinical setting. We provide an easy-to-use single protocol successfully evaluated for the characterization of a broad and representative panel of DNA and RNA respiratory viruses in various types of clinical samples.

Benzodiazepine dose reduction in prisoner patients: 15 years' teamwork between psychiatrists and pharmacists.

WHAT IS KNOWN AND OBJECTIVE: Benzodiazepines are widely consumed in prisons, despite the iatrogenic risks associated with this therapeutic class. A multidisciplinary pharmacotherapy programme was therefore initiated by pharmacists in 2001. The aim of this study was to demonstrate the efficacy of teamwork between psychiatrists and pharmacists in benzodiazepine dose adjustment, with 15 years of hindsight. METHOD: In this retrospective study, daily prescribed benzodiazepine doses were compared between a reference group of patients in prisons in Lyon, France, in 2000, and four groups after psychiatrist-pharmacist teamwork in 2004, 2008, 2012 and 2016. RESULTS AND DISCUSSION: A number of 1249 patients were included. Prescribed doses of benzodiazepine decreased in the intervention groups, to a mean of 29-35 mg diazepam equivalent per day, compared to the control group (42 mg/day) (P < .001). The first 4-year period (2000-2004) demonstrated that monthly meetings and systematic pharmaceutical medication review had an impact on prescribed benzodiazepines, limiting consumed doses. The others (2004-2008, 2008-2012 and 2012-2016) confirmed that physicians' adherence to prescription guidelines and the efficacy of pharmacotherapy programme was maintained, particularly in those inmates taking high doses. WHAT IS NEW AND CONCLUSION: A continuous quality programme conducted by psychiatrists and pharmacists showed positive impact in reducing doses of benzodiazepine prescribed to prisoner patients and contributing to reduce risk of benzodiazepine-related problems.

Influence of the emollient on emulsions containing lamellar liquid crystals: from molecular organization towards applicative properties.

OBJECTIVE: The sensory perception of cosmetic emulsions is complex as it is governed by an important number of parameters like the choice of raw materials, their interactions, the structural organisation of the system, etc. The aim of the present work was to go further in the interpretation of the emollient-surfactant interactions, towards the emulsions applicative properties. For this purpose, two systems containing liquid crystals of the lamellar type were formulated, differing only in the selected emollient. METHODS: First, the liquid crystals types were checked using different tools like the optical microscopy under the bright and polarized light, the wide-angle X rays diffraction and, finally, thermogravimetric analysis. Next, two sensory attributes, namely compression force and difficulty of spreading, were evaluated by a sensory panel. In addition to that, complementary instrumental characterizations (flow tests, textural analysis and contact angle measurements) were performed in order to understand how the panel could discriminate the products. RESULTS: The results showed that isohexadecane emollient induces the α-gel structures, while caprylic capric triglycerides favour the formation of the lamellar liquid crystals near to α-gel. For the compression force, the results point out that there is no direct interaction between the oil phase and the skin. For this attribute, depending on its chemical structure, emollient impacts the human perception only by changing the lamellar phase type. Concerning the difficulty of spreading, both the emulsion structure and the emollient properties should be considered. Immediate perception is impacted by the emulsions destruction, making the droplet roll one on each other. Then, once the droplets monolayer is disrupted, the emollient comes into direct contact with the skin. In this case, the perception is governed by the direct affinity of the emollient with the skin, nonpolar emollients being easier to spread if compared to polar ones. CONCLUSION: The sensory perception is guided not only by the choice of the raw materials but also by their interactions. It was shown that the chemical structure of the emollients affected the molecular organization of liquid crystals present in the emulsion and, consequently, directly or indirectly its sensory perception.

Antibody-Mediated Rejection in Lung Transplantation: Clinical Outcomes and Donor-Specific Antibody Characteristics.

In the context of lung transplant (LT), because of diagnostic difficulties, antibody-mediated rejection (AMR) remains a matter of debate. We retrospectively analyzed an LT cohort at Foch Hospital to demonstrate the impact of AMR on LT prognosis. AMR diagnosis requires association of clinical symptoms, donor-specific antibodies (DSAs), and C4d(+) staining and/or histological patterns consistent with AMR. Prospective categorization split patients into four groups: (i) DSA positive, AMR positive (DSA(pos) AMR(pos) ); (ii) DSA positive, AMR negative (DSA(pos) AMR(neg) ); (iii) DSA limited, AMR negative (DSA(Lim) ; equal to one specificity, with mean fluorescence intensity of 500-1000 once); and (iv) DSA negative, AMR negative (DSA(neg) ). AMR treatment consisted of a combination of plasmapheresis, intravenous immunoglobulin and rituximab. Among 206 transplanted patients, 10.7% were DSA(pos) AMR(pos) (n = 22), 40.3% were DSA(pos) AMR(neg) (n = 84), 6% were DSA(Lim) (n = 13) and 43% were DSA(neg) (n = 88). Analysis of acute cellular rejection at month 12 showed higher cumulative numbers (mean plus or minus standard deviation) in the DSA(pos) AMR(pos) group (2.1 ± 1.7) compared with DSA(pos) AMR(neg) (1 ± 1.2), DSA(Lim) (0.75 ± 1), and DSA(neg) (0.7 ± 1.23) groups. Multivariate analysis demonstrated AMR as a risk factor for chronic lung allograft dysfunction (hazard ratio [HR] 8.7) and graft loss (HR 7.56) for DSA(pos) AMR(pos) patients. Our results show a negative impact of AMR on LT clinical course and advocate for an early active diagnostic approach and evaluation of therapeutic strategies to improve prognosis.

HLA-G*01:04∼UTR3 Recipient Correlates With Lower Survival and Higher Frequency of Chronic Rejection After Lung Transplantation.

Lung transplantation (LTx) is a valid therapeutic option for selected patients with end-stage lung disease. Soluble HLA-G (sHLA-G) has been associated with increased graft survival and decreased rejection episodes in solid organ transplantation. HLA-G haplotypes named UTRs, defined by SNPs from both the 5'URR and 3'UTR, have been reported to reliably predict sHLA-G level. The aim of this retrospective study was to determine the impact of HLA-G alleles and UTR polymorphism from LTx recipients on anti-HLA allo-immunization risk, overall survival and chronic rejection (CLAD). HLA-G SNPs were genotyped in 124 recipients who underwent LTx from 1996 to 2010 in Marseille, 123 healthy individuals and 26 cystic fibrosis patients not requiring LTx. sHLA-G levels were measured for 38 LTx patients at D0, M3 and M12 and for 123 healthy donors. HLA-G*01:06∼UTR2 was associated with a worse evolution of cystic fibrosis (p = 0.005) but not of long-term survival post-LTx. HLA-G*01:04∼UTR3 haplotype was associated with lower levels of sHLA-G at D0 and M3 (p = 0.03), impaired long-term survival (p = 0.001), increased CLAD occurrence (p = 0.03) and the production of de novo donor-specific antibodies (DSA) at M3 (p = 0.01). This study is the first to show the deleterious association of different HLA-G alleles and UTRs in LTx.

Value of allohaemagglutinins in the diagnosis of a polysaccharide antibody deficiency.

Polysaccharide antibody deficiency is characterized by a poor or absent antibody response after vaccination with an unconjugated pneumococcal polysaccharide vaccine. Allohaemagglutinins (AHA) are antibodies to A or B polysaccharide antigens on the red blood cells, and are often used as an additional or alternative measure to assess the polysaccharide antibody response. However, few studies have been conducted to establish the clinical significance of AHA. To investigate the value of AHA to diagnose a polysaccharide antibody deficiency, pneumococcal polysaccharide antibody titres and AHA were studied retrospectively in 180 subjects in whom both tests had been performed. Receiver operating characteristic curves for AHA versus the pneumococcal vaccine response as a marker for the anti-polysaccharide immune response revealed an area under the curve between 0·5 and 0·573. Sensitivity and specificity of AHA to detect a polysaccharide antibody deficiency, as diagnosed by vaccination response, were low (calculated for cut-off 1/4-1/32). In subjects with only low pneumococcal antibody response, the prevalence of bronchiectasis was significantly higher than in subjects with only low AHA (45·5 and 1·3%, respectively) or normal pneumococcal antibody response and AHA (2·4%). A logistic regression model showed that low pneumococcal antibody response but not AHA was associated with bronchiectasis (odds ratio 46·2). The results of this study do not support the routine use of AHA to assess the polysaccharide antibody response in patients with suspected immunodeficiency, but more studies are warranted to clarify the subject further.

Chronic active Epstein-Barr virus infection with cutaneous and sinus lymphoproliferation in a white female patient with 25 years' follow-up: an original case report.

Chronic active Epstein-Barr virus infection (CAEBV) is characterized by chronic infectious mononucleosis-like symptoms associated with very high viral load, as assessed by quantitative polymerase chain reaction. We present an unusual case in a French woman who was followed up over 25 years with cutaneous and sinus lymphoproliferation. This white woman presented with a long history of recurrent cutaneous necrotic papules of the skin, which started during childhood and healed spontaneously with depressed scars. The lesions spread to the left maxillary sinus and were associated with hepatomegaly and splenomegaly with no other visceral locations. Pathological examination of the skin and sinus revealed a dermal monoclonal T-cell lymphoproliferative disorder, CD7(+) and CD20(-) , with no epidermotropism. T-cell receptor rearrangement was positive, showing the monoclonality from the first biopsy. This T-cell proliferation was positive for EBV-encoded small RNA and was associated with a high EBV viral load. Since then, the patient has been in good health, despite a permanently high EBV viral load. Hydroa vacciniforme (HV)-like lymphoma and natural killer/T-cell lymphoma were discussed, but none really fit our case. Natural killer cell lymphoma was ruled out because of the indolent course, but sinus lesions do not exist in HV-like lymphoma. A therapeutic approach is difficult because of the coexistence of viral infection and monoclonal T-cell proliferation. Chemotherapy is not efficient and induces immunosuppression, which may worsen the prognosis. Although rituximab may have an immunomodulatory function, it was not effective in our case.

Pathophysiology and treatment of typical and atypical hemolytic uremic syndrome.

Hemolytic uremic syndrome is a rare disease, frequently responsible for renal insufficiency in children. Recent findings have led to renewed interest in this pathology. The discovery of new gene mutations in the atypical form of HUS and the experimental data suggesting the involvement of the complement pathway in the typical form, open new perspectives for treatment. This review summarizes the current state of knowledge on both typical and atypical hemolytic uremic syndrome pathophysiology and examines new perspectives for treatment.