Clinical spectrum and outcome of Takayasu's arteritis in children.

OBJECTIVES: We aimed to compare clinical spectrum and outcome between adults and children with Takayasu's arteritis (TAK) in a European population. METHODS: We made a nationwide retrospective observational study between 1988 and 2019. All adult patients met the ACR diagnostic criteria for TAK and all children met the EULAR/PRINTO/PRES criteria for paediatric TAK. RESULTS: We identified 46 children and 389 adults with TAK. The male to female ratio was 34/46 (0.74) in the paediatric group compared to 241/274 (0.88) in the adult group (P<0.05). Children presented with significantly more systemic symptoms; i.e., fever (P<0.05), fatigue (P<0.001), weight loss (P<0.001), abdominal pain (P<0.05), and myalgia (P<0.05) while adults had more upper limb claudication (P<0.01). Topography of the lesions differed significantly between the two groups: adults had more damage at the cerebral vasculature (P<0.01), upper and lower limbs (P<0.001) while children had more kidney lesions (P<0.05). Children TAK had more frequent (P<0.01) and higher (P<0.001) biological inflammation than adults. Children received higher dose-weight of corticosteroids (P=0.001) and less biotherapy (P<0.010) at diagnosis. Relapses (P<0.05) and death (8.6% vs 4.9%) were more frequent in children TAK than in adults. CONCLUSION: Paediatric TAK seems more severe than adult TAK. Therefore, paediatrics patients may require closer monitoring and systemic use of biological treatment.

Strengths and limitations of reduced representation bisulfite sequencing (RRBS) in the perspective of DNA methylation analysis in fish: a case-study on rainbow trout spermatozoa.

DNA methylation in CpG dinucleotides is an important epigenetic mark in fish spermatozoa since it has been shown that some sperm methylome features are transmitted to the offspring. Reduced representation bisulfite sequencing (RRBS) is one genome-scale methods developed to assess DNA methylation at CpG sites. It allows the sequencing of a reduced fraction of the genome expected to be enriched in CpGs. The aim of this study is to characterize the extent of the CpG sites that can be identified in the RRBS-reduced sequenced fraction of rainbow trout spermatozoa, in order to evaluate the potential of RRBS for sperm DNA methylation studies. We observed that RRBS did provide a reduced amount of genomic data, the sum of the CpGs analyzed on 12 males spanning 9% of the total genomic CpGs. CpGs were only slightly enriched in the RRBS data (×1.7 times the sequenced nucleotides), the possible causes being linked to trout genome structure and sequenced fragments size. All genomic functional features were represented in our CpG dataset, with a noticeable enrichment in exons but, strikingly, not in promoters. The number of CpGs shared between biological replicates was low, but this proportion reached workable values from six biological replicates (46% of the analyzed cytosines) on. The choices that are to be made regarding fragment size selection and the options during bioinformatic data processing are discussed. In all, RRBS is a relevant first-approach method to scan the CpG DNA methylation status of spermatozoa along rainbow trout genome, although in a very reduced pattern among biological replicates.

Attitudes and Behaviors towards Food and Weight in Late Pregnancy: A Comparative Approach between Individuals with and without Previous Bariatric Surgery.

The aims of this study were to compare, between pregnant individuals with and without bariatric surgery: (1) eating behaviors, (2) intuitive eating components and, (3) attitudes towards weight gain. This retrospective study included data collected in healthy pregnant individuals with and without previous bariatric surgery who were recruited at the Centre Hospitalier Universitaire (CHU) de Québec-Université Laval. Pregnant individuals who underwent bariatric surgery (biliopancreatic bypass with duodenal switch [n = 14] or sleeve gastrectomy [n = 5]) were individually matched, for age (±0.4 years) and body mass index (BMI) (±0.3 kg/m2), with pregnant individuals who have not received bariatric surgery. In the second trimester, participants completed the Three Factor Eating Questionnaire (TFEQ) and the Intuitive Eating Scale 2 (IES-2). In the third trimester, participants completed the French version of the Pregnancy Weight Gain Attitude Scale assessing attitudes towards weight gain. Pregnant individuals who have had bariatric surgery had a higher score for flexible restraint and a lower score for situational susceptibility to disinhibition compared to individuals who have not had undergone bariatric surgery (2.89 ± 1.15 vs. 1.95 ± 1.31; p = 0.04 and 1.11 ± 1.29 vs. 2.79 ± 1.44, respectively; p < 0.001). Regarding intuitive eating, pregnant individuals who experienced bariatric surgery had a higher score for reliance on internal hunger and satiety cues and a lower one for unconditional permission to eat compared with those who had not experienced bariatric surgery (3.99 ± 0.81 vs. 3.30 ± 1.03; p = 0.02 and 3.28 ± 0.54 vs. 3.61 ± 0.68, respectively; p = 0.03). No difference in attitudes towards weight gain was observed between groups. Overall, pregnant individuals who had undergone bariatric surgery had different eating behaviors and intuitive eating components compared to pregnant individuals without bariatric surgery. These results need to be confirmed in further studies with larger sample sizes.

Genome-wide comparative methylation analysis reveals the fate of germ stem cells after surrogate production in teleost.

BACKGROUND: Surrogate production by germline stem cell transplantation is a powerful method to produce donor-derived gametes via a host, a practice known as surrogacy. The gametes produced by surrogates are often analysed on the basis of their morphology and species-specific genotyping, which enables conclusion to be drawn about the donor's characteristics. However, in-depth information, such as data on epigenetic changes, is rarely acquired. Germ cells develop in close contact with supporting somatic cells during gametogenesis in vertebrates, and we hypothesize that the recipient's gonadal environment may cause epigenetic changes in produced gametes and progeny. Here, we extensively characterize the DNA methylome of donor-derived sperm and their intergenerational effects in both inter- and intraspecific surrogates. RESULTS: We found more than 3000 differentially methylated regions in both the sperm and progeny derived from inter- and intraspecific surrogates. Hypermethylation in the promoter regions of the protocadherin gamma gene in the intraspecific surrogates was found to be associated with germline transmission. On the contrary, gene expression level and the embryonic development of the offspring remained unaffected. We also discovered MAPK/p53 pathway disruption in interspecific surrogates due to promoter hypermethylation and identified that the inefficient removal of meiotic-arrested endogenous germ cells in hybrid gonads led to the production of infertile spermatozoa. CONCLUSIONS: Donor-derived sperm and progeny from inter- and intraspecific surrogates were more globally hypermethylated than those of the donors. The observed changes in DNA methylation marks in the surrogates had no significant phenotypic effects in the offspring.

Cryopreservation effect on DNA methylation profile in rainbow trout spermatozoa.

Spermatozoa are the cells that are most commonly used for cryopreservation of valuable genetic resources in aquaculture. It is known that fish spermatozoa transmit to the embryo not only their genetic but also their epigenetic profile, especially DNA methylation. Therefore, any alteration of the DNA methylation profile in spermatozoa induces the risk of transmitting epigenetic alterations to the offspring. The aim of this study was to assess the effect of cryopreservation on DNA methylation in rainbow trout spermatozoa. To trigger variable cellular response after freezing-thawing, spermatozoa from mature males were cryopreserved with dimethyl sulfoxide, methanol or glycerol as cryoprotectant. We observed that dimethyl sulfoxide was the best to preserve thawed spermatozoa functions. Methanol only slightly preserved all the cellular parameters, while glycerol failed to protect motility and fertilization ability. The consequences on DNA methylation were assessed using Reduced Representation Bisulfite Sequencing (RRBS). Sperm cryopreservation did not thoroughly impact DNA methylation, although 335-564 differentially methylated cytosines were characterized depending on the cryoprotectant. Very few of them were shared between cryoprotectants, and no correlation with the extent of cellular damage was found. Our study showed that DNA methylation was only slightly altered after sperm cryopreservation, and this may render further analysis of the risk for the progeny very challenging.

[Childhood-onset systemic lupus]. / Lupus systémique de l'enfant.

CHILDHOOD-ONSET SYSTEMIC LUPUS. Childhood-onset systemic lupus (SL) is a rare multifactorial autoimmune disease belonging to connectivitis. Clinical presentation is very heterogeneous with multi-systemic involvement: skin, joint, renal, hematological, neuropsychiatric, pulmonary, cardiac among others. Renal involvement is particularly frequent and severe in children and must be checked ou on a regular basis by screening for proteinuria. Lab exams show the production of antibodies directed against the native double-stranded DNA, excessive production of type I interferon, consumption of complement is observed during periods of flare-up. There are rare forms of monogenic SL which must be evocated in case of early-onset, familial cases or when occurring in boys.

LUPUS SYSTÉMIQUE DE L'ENFANT. Le lupus systémique (LS) de l'enfant est une maladie auto-immune multifactorielle rare appartenant aux connectivites. Sa présentation clinique est très hétérogène, avec des atteintes multisystémiques : cutanées, articulaires, rénales, hématologiques, neuropsychiatriques, pulmonaires, cardiaques, entre autres. L'atteinte rénale est particulièrement fréquente et sévère chez l'enfant et doit être dépistée régulièrement par la recherche de protéinurie. Biologiquement, le LS se caractérise par la production d'anticorps dirigés contre l'ADN natif double brin et une production excessive d'interféron de type I ; une consommation du complément est constatée lors des périodes de poussée. Il existe des formes rares de LS monogénique, qui doivent être évoquées devant le caractère précoce de la maladie ou chez le garçon.

Extra-osseous manifestations in chronic recurrent multifocal osteomyelitis: a retrospective study.

OBJECTIVES: Extra-osseous (EO) manifestations are poorly characterized in chronic recurrent multifocal osteomyelitis (CRMO). This study aimed to further define the frequency, characteristics and treatment of EO events in CRMO and whether different phenotypes can be distinguished and benefit from special management. METHODS: This multicentre retrospective study included CRMO patients followed in several paediatric rheumatology departments in France, between 2015 and 2022. EO manifestations were defined as skin lesions, gastrointestinal manifestations, arthritis, enthesitis, sacroiliitis, uveitis, vasculitis, and fever. At the last visit, the physician defined CRMO as active in the presence of clinical manifestations including both osseous and EO symptoms. RESULTS: We included 133 patients; 87 (65.4%) were girls; the median age at first symptoms was 9.0 years (interquartile range 7.0-10.0). EO manifestations were described in 90 (67.7%) patients, with a predominance of skin lesions (n = 51/90; 56.7%), followed by sacroiliitis (n = 38/90; 42.2%), enthesitis (n = 21/90; 23.3%), arthritis (n = 14/90, 15.6%) and gastrointestinal manifestations (n = 6/90, 6.7%). The use of non-steroidal anti-inflammatory drugs and bisphosphonates did not differ by presence or not of EO manifestations. Biologics were taken more frequently by patients with than without EO manifestations (p< 0.001); tumour necrosis factor inhibitors were used in 33 (36.7%) EO+ patients. Under this treatment, 18 (54.5%) patients achieved complete remission of osseous and EO manifestations. At the last visit, more EO-positive than EO-negative patients were on treatment (p= 0.009), with active disease in 58 (64.4%) patients. CONCLUSION: The analysis of EO manifestations in CRMO delineates 2 groups of patients in terms of severity and treatments used. Our study opens up new pathophysiological leads that may underlie the wide range of CRMO phenotypes.

Conserved and divergent arms of the antiviral response in the duplicated genomes of salmonid fishes.

Antiviral innate immunity is orchestrated by the interferon system, which appeared in ancestors of jawed vertebrates. Interferon upregulation induces hundreds of interferon-stimulated-genes (ISGs) with effector or regulatory functions. Here we investigated the evolutionary diversification of ISG responses through comparison of two salmonid fishes, accounting for the impact of sequential whole genome duplications ancestral to teleosts and salmonids. We analysed the transcriptomic response of the IFN pathway in the head kidney of rainbow trout and Atlantic salmon, which separated 25-30 Mya. We identified a large set of ISGs conserved in both species and cross-referenced them with zebrafish and human ISGs. In contrast, around one-third of salmonid ISG lacked orthologs in human, mouse, chicken or frog, and often between rainbow trout and Atlantic salmon, revealing a fast-evolving, lineage-specific arm of the antiviral response. This study also provides a key resource for in-depth functional analysis of ISGs in salmonids of commercial significance.

Spermatozoa methylome and its sensitivity to water temperature in a teleost fish.

Global climate change and heat waves are sources of stress which fish are facing in the wild as well as in aquaculture context. In coping with important environmental variations, they demonstrate a great plasticity and a tendency for acclimation throughout generations. Here, we question whether fish might be prone to transmit epigenetic alterations through their gametes to their offspring, thus driving rapid environmental adaptation. The question of epigenetic inheritance in fish has become of crucial interest in the recent years, when the mammalian model of methylome erasure in germ cells and embryos was found not to be conserved. In this work, by sequencing spermatozoa after bisulfite conversion, we characterized the methylation landscape of the paternal gamete in rainbow trout (in comparison to muscle) before to demonstrate its sensitivity to a 4 °C increased rearing temperature during spermatogenesis. We found that spermatozoa methylome specifically primes housekeeping and developmental genes for activation and might be instrumental to early development. Most of these methylation-free promoters were not affected by temperature, attesting the robustness of the epigenetic programming of early development. However, the increase of temperature triggered the differential methylation of 5359 regions, among which 560 gene promoters control spermiogenesis and lipid metabolism. We therefore report, for the first time in fish, that sperm epigenetic landscape carries marks of parental thermal living conditions, suggesting that DNA methylation might be a molecular basis of intergenerational inheritance.

International cohort of 382 children with lupus nephritis - presentation, treatment and outcome at 24 months.

BACKGROUND: Children with lupus have a higher chance of nephritis and worse kidney outcome than adult patients. METHODS: We retrospectively analyzed clinical presentation, treatment and 24-month kidney outcome in a cohort of 382 patients (≤ 18 years old) with lupus nephritis (LN) class ≥ III diagnosed and treated in the last 10 years in 23 international centers. RESULTS: The mean age at onset was 11 years 9 months and 72.8% were females. Fifty-seven percent and 34% achieved complete and partial remission at 24-month follow-up, respectively. Patients with LN class III achieved complete remission more often than those with classes IV or V (mixed and pure). Only 89 of 351 patients maintained stable complete kidney remission from the 6th to 24th months of follow-up. eGFR ≥ 90 ml/min/1.73 m2 at diagnosis and biopsy class III were predictive of stable kidney remission. The youngest and the oldest age quartiles (2y-9y, 5m) (14y, 2m-18y,2m) showed lower rates of stable remission (17% and 20.7%, respectively) compared to the two other age groups (29.9% and 33.7%), while there was no difference in gender. No difference in achieving stable remission was found between children who received mycophenolate or cyclophosphamide as induction treatment. CONCLUSION: Our data show that the rate of complete remission in patients with LN is still not high enough. Severe kidney involvement at diagnosis was the most important risk factor for not achieving stable remission while different induction treatments did not impact outcome. Randomized treatment trials involving children and adolescents with LN are needed to improve outcome for these children. A higher resolution version of the Graphical abstract is available as Supplementary information.

Rescue of Pap-Mas in Systemic JIA Using Janus Kinase Inhibitors, Case Report and Systematic Review.

INTRODUCTION: Biological disease-modifying anti-rheumatic drugs (bDMARDs) targeting interleukin (IL)-6 and IL-1ß represent a steroid-sparing first-line therapy used in systemic-onset juvenile idiopathic arthritis (sJIA). Recently, the occurrence of pulmonary alveolar proteinosis (PAP) in sJIA patients was reported with early-onset and exposure to bDMARDs as potential risk factors. We report on a new case with longitudinal immunomonitoring successfully treated by Janus Kinase inhibitors (JAKi) and review past clinical descriptions of this new entity. METHODS: We report one case of pulmonary alveolar proteinosis and macrophage activation syndrome (PAP-MAS) with longitudinal immunomonitoring. We then conducted a review of the literature of seven publications reporting 107 cases of PAP-MAS sJIA, and included the main characteristics and evolution under treatment. RESULTS: Of the seven articles analyzed, the incidence of PAP-MAS among sJIA patients varied from 1.28% to 12.9%. We report here a single case among a cohort of 537 sJIA patients followed in the pediatric department of the Hospices Civils de Lyon over the last 15 years. This child presented with all clinical and immunological characteristics of PAP-MAS. After several lines of treatment, he benefited from JAKi and improved with respect to both systemic symptoms and lung disease. In the literature, strategies with monoclonal antibodies targeting either INF-γ or IL-1ß/IL-18 have been tested with variable results. Orally taken JAKi presents the advantage of targeting multiple cytokines and avoiding parenteral injections of monoclonal antibodies that may contribute to the pathogenesis. CONCLUSIONS: JAKi represent a promising option in the treatment of lung disease associated with sJIA.

Evaluation of Slowfade Diamond as a buffer for STORM microscopy.

We study the potential of the commercial mounting medium Slowfade diamond as a buffer for STORM microscopy. We show that although it does not work with the popular far-red dyes typically used for STORM imaging, such as Alexa Fluor 647, it performs really well with a wide variety of green-excited dyes such as Alexa Fluor 532, Alexa Fluor 555 or CF 568. Moreover, imaging can be performed several months after the samples are mounted in this environment and kept in the fridge, providing a convenient way to preserve samples for STORM imaging, as well as to keep calibration samples, for example for metrology or teaching in particular in imaging facilities.

Higher Than Recommended Folic Acid Intakes is Associated with High Folate Status Throughout Pregnancy in a Prospective French-Canadian Cohort.

BACKGROUND: Folate and vitamin B12 status during pregnancy are important for maternal and neonatal health. Maternal intake and prepregnancy body mass index (ppBMI) can influence biomarker status. OBJECTIVES: This study aimed to, throughout pregnancy; 1) assess folate and B12 status including serum total folate, plasma total vitamin B12, and homocysteine (tHcy); 2) examine how these biomarkers are associated with intakes of folate and B12 and with ppBMI; and 3) determine predictors of serum total folate and plasma total vitamin B12. METHODS: In each trimester (T1, T2, and T3), food and supplement intakes of 79 French-Canadian pregnant individuals were assessed by 3 dietary recalls (R24W) and a supplement use questionnaire. Fasting blood samples were collected. Serum total folate and plasma total vitamin B12 and tHcy were assessed by immunoassay (Siemens ADVIA Centaur XP). RESULTS: Participants were 32.1 ± 3.7 y and had a mean ppBMI of 25.7 ± 5.8 kg/m2. Serum total folate concentrations were high (>45.3 nmol/L, T1: 75.4 ± 55.1, T2: 69.1 ± 44.8, T3: 72.1 ± 52.1, P = 0.48). Mean plasma total vitamin B12 concentrations were >220 pmol/L (T1: 428 ± 175, T2: 321 ± 116, T3: 336 ± 128, P < 0.0001). Mean tHcy concentrations were <11 µmol/L across trimesters. Most participants (79.6%-86.1%) had a total folic acid intake above the Tolerable Upper Intake Level (UL, >1000 µg/d). Supplement use accounted for 71.9%-76.1% and 35.3%-41.8% of total folic acid and vitamin B12 intakes, respectively. The ppBMI was not correlated with serum total folate (P > 0.1) but was weakly correlated with and predicted lower plasma total vitamin B12 in T3 (r = -0.23, P = 0.04; r2 = 0.08, standardized beta [sß] = -0.24, P = 0.01). Higher folic acid intakes from supplements predicted higher serum total folate (T1: r2 = 0.05, sß = 0.15, P = 0.04, T2: r2 = 0.28, sß = 0.56, P = 0.01, T3: r2 = 0.19, sß = 0.44, P < 0.0001). CONCLUSIONS: Most pregnant individuals had elevated serum total folate concentrations, reflecting total folic acid intakes above the UL driven by supplement use. Vitamin B12 concentrations were generally adequate and differed by ppBMI and pregnancy stage.

Health-Related Preconception Factors: Adherence to Guidelines and Associations with Weight Status.

BACKGROUND: Knowing the percentage of women planning a pregnancy who meet preconception dietary and physical activity (PA) guidelines and which health-related preconception factors are associated with body mass index (BMI) could help improve preconception care. OBJECTIVES: In a study conducted in women who were planning to conceive, the aims were to describe and compare eating and PA habits to current guidelines, as well as to identify the factors associated with BMI. DESIGN: This was a cross-sectional study. PARTICIPANTS/SETTING: From 2017 to 2020, women planning to conceive within the next year (n = 217) were recruited in the province of Québec (Canada) to participate in the Apports Nutritionnels durant la GrossessE - Cohorte Contrôle study. Among them, 184 (84.8%) were included in the analyses. MAIN OUTCOME MEASURES: Women completed three (90.2%) or two (9.8%) Web-based 24-hour dietary recalls and the International Physical Activity Questionnaire. Weight and height as well as the presence/absence of weight/body image concerns were self-reported. Eating and PA habits were compared with dietary reference intakes and Canadian guidelines, respectively. STATISTICAL ANALYSES: Descriptive statistics were used to describe the sample, eating and PA habits, as well as adherence to guidelines. A multivariable regression analysis was performed to identify the factors associated with BMI. RESULTS: On average, women were aged 30.8 ± 4.1 years and identified as White (94.0%). Most of them had weight/body image concerns (58.7%), 54.6% of whom had a normal body weight. Overall, 42.3% engaged in 150 minutes/week or more of moderate-to-vigorous intensity PA and 84.8% consumed <135 g alcoholic beverages per week. Mean dietary intake was below Dietary Reference Intakes for carbohydrates, vitamins D and E, and above Dietary Reference Intakes for total fat and folic acid. Factors associated with a higher BMI were weight/body image concerns (ß = 1.83; R2 = 13.0%), higher dietary protein intake (ß = .05; R2 = 4.0%), lower income (ß = .85; R2 = 2.9%), no folic acid supplementation (ß = .83; R2 = 2.5%), spending less time in moderate-to-vigorous intensity PA (ß = -.006; R2 = 2.4%), eating <2 snacks (ß = .75; R2 = 2.2%), and <3 meals (ß = 1.38; R2 = 1.5%) daily. CONCLUSION: Women planning to conceive do not have optimal eating and PA behaviors. Modifiable factors associated with BMI in preconception were identified.

TET2-mediated epigenetic reprogramming of breast cancer cells impairs lysosome biogenesis.

Methylation and demethylation of cytosines in DNA are believed to act as keystones of cell-specific gene expression by controlling the chromatin structure and accessibility to transcription factors. Cancer cells have their own transcriptional programs, and we sought to alter such a cancer-specific program by enforcing expression of the catalytic domain (CD) of the methylcytosine dioxygenase TET2 in breast cancer cells. The TET2 CD decreased the tumorigenic potential of cancer cells through both activation and repression of a repertoire of genes that, interestingly, differed in part from the one observed upon treatment with the hypomethylating agent decitabine. In addition to promoting the establishment of an antiviral state, TET2 activated 5mC turnover at thousands of MYC-binding motifs and down-regulated a panel of known MYC-repressed genes involved in lysosome biogenesis and function. Thus, an extensive cross-talk between TET2 and the oncogenic transcription factor MYC establishes a lysosomal storage disease-like state that contributes to an exacerbated sensitivity to autophagy inducers.

Defining renal remission in an international cohort of 248 children and adolescents with lupus nephritis.

OBJECTIVE: We studied the rate of remission of LN in an international cohort of 248 children and adolescents with biopsy-proven LN. Five different definitions from scientific studies and the definitions recommended by the ACR and Kidney Disease: Improving Global Outcomes were used. METHODS: Anonymized clinical data in patients with biopsy-proven LN class ≥III (International Society of Nephrology/Royal Pathology Society) diagnosed and treated in the last 10 years in 23 international centres from 10 countries were collected. We compared the rate of patients in complete and partial remission applying the different definitions. RESULTS: The mean age at diagnosis was 11 years and 4 months, and 177 were females. The number of patients in complete and partial remission varied a great deal between the different definitions. At 24 months, between 50% and 78.8% of the patients were in full remission as defined by the different criteria. The number of patients in partial remission was low, between 2.3% and 25%. No difference in achieved remission was found between boys and girls or between children and adolescents (P > 0.05). Patients with East Asian ethnicity reached remission more often than other ethnicities (P = 0.03-0.0008). Patients treated in high-income countries showed a higher percentage of complete remission at 12 and 24 months (P = 0.002-0.000001). CONCLUSION: The rate of children and adolescents with LN achieving remission varied hugely with the definition used. Our results give important information for long-awaited treatment studies in children and young people.

NLRC4 GOF Mutations, a Challenging Diagnosis from Neonatal Age to Adulthood.

The NLRC4 inflammasome is part of the human immune innate system. Its activation leads to the cleavage of pro-inflammatory cytokines IL-1ß and IL-18, promoting inflammation. NLRC4 gain-of-function (GOF) mutations have been associated with early-onset recurrent fever, recurrent macrophagic activation syndrome and enterocolitis. Herein, we describe two new patients with NLRC4 mutations. The first case presented with recurrent fever and vasoplegic syndrome, gut symptoms and urticarial rashes initially misdiagnosed as a severe protein-induced enterocolitis syndrome. The second case had recurrent macrophage activation syndrome (MAS) and shock, suggesting severe infection. We identified two NLRC4 mutations, on exon 4, within the nucleotide-binding protein domain (NBD). After a systematic review of NLRC4 GOF mutations, we highlight the wide spectrum of this disease with a limited genotype-phenotype correlation. Vasoplegic shock was only reported in patients with mutation in the NBD. Diagnosing this new entity combined with gastrointestinal symptoms and vasoplegic shocks is challenging. It mimics severe allergic reaction or sepsis. The plasma IL-18 level and genetic screening are instrumental to make a final diagnosis.

Disseminated bartonellosis in a child with steroid-dependent nephrotic syndrome receiving mycophenolate mofetil monotherapy.

Cat scratch disease, usually a benign infectious disease, may develop as multisystem disease with multiorgan involvement, particularly in immunocompromised patients. We report on a patient who developed disseminated bartonellosis while receiving mycophenolate mofetil monotherapy treating steroid-dependent nephrotic syndrome, highlighting that severe infection can be observed in those patients. Therefore, this category of patients should be cautious when having contact with kittens and receives proper prevention advice.