References of "Moutschen, Michel"
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See detailEtude des motifs d'admission au service des Urgences d'une cohorte de patients
Pirotte, Benoit; FRIPPIAT, Frédéric ULiege; DARCIS, Gilles ULiege et al

in Revue Médicale de Liège (2019)

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See detailGrowth hormone (GH) deficient mice with GHRH ablation are severely deficient in vaccine and immune responses against Streptococcus pneumoniae
Farhat, Khalil; Bodart, Gwennaëlle ULiege; Moutschen, Michel ULiege et al

in Acta Clinica Belgica (2018, December), 73(6 (Suppl.2)),

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See detailGrowth hormone (GH) deficient mice with GHRH ablation are severely deficient in vaccine and immune responses against Streptococcus pneumoniae
Farhat, Khalil; Bodart, Gwennaëlle ULiege; Charlet-Renard, Jeanne de Chantal ULiege et al

in Frontiers in Immunology (2018), 9

The precise impact of the somatotrope axis upon the immune system is still highly debated. We have previously shown that mice with generalized ablation of growth hormone (GH) releasing hormone (GHRH) gene ... [more ▼]

The precise impact of the somatotrope axis upon the immune system is still highly debated. We have previously shown that mice with generalized ablation of growth hormone (GH) releasing hormone (GHRH) gene (Ghrh−/−) have normal thymus and T-cell development, but present a marked spleen atrophy and B-cell lymphopenia. Therefore, in this paper we have investigated vaccinal and anti-infectious responses of Ghrh−/− mice against S. pneumoniae, a pathogen carrying T-independent antigens. Ghrh−/− mice were unable to trigger production of specific IgM after vaccination with either native pneumococcal polysaccharides (PPS, PPV23) or protein-PPS conjugate (PCV13). GH supplementation of Ghrh−/− mice restored IgM response to PPV23 vaccine but not to PCV13 suggesting that GH could exert a specific impact on the spleen marginal zone that is strongly implicated in T-independent response against pneumococcal polysaccharides. As expected, after administration of low dose of S. pneumoniae, wild type (WT) completely cleared bacteria after 24 h. In marked contrast, Ghrh−/− mice exhibited a dramatic susceptibility to S. pneumoniae infection with a time-dependent increase in lung bacterial load and a lethal bacteraemia already after 24 h. Lungs of infected Ghrh−/− mice were massively infiltrated by inflammatory macrophages and neutrophils, while lung B cells were markedly decreased. The inflammatory transcripts signature was significantly elevated in Ghrh−/− mice. In this animal model, the somatotrope GHRH/GH/IGF1 axis plays a vital and unsuspected role in vaccine and immunological defense against S. pneumoniae. [less ▲]

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See detailGHRH-deleted Mice Are Severely Deficient in Vaccine And Immunological Responses Against Streptococcus Pneumoniae
Farhat, Khalil ULiege; Bodart, Gwennaëlle ULiege; Desmet, Christophe ULiege et al

Conference (2018, March 20)

Background and objective of the work. Ghrh-/- mice with a severe deficiency of their somatotrope GHRH/GH/IGF1 axis (1) are resistant to experimental allergic encephalomyelitis (2). In basal conditions ... [more ▼]

Background and objective of the work. Ghrh-/- mice with a severe deficiency of their somatotrope GHRH/GH/IGF1 axis (1) are resistant to experimental allergic encephalomyelitis (2). In basal conditions, thymus and T-cell development are not severely affected but a marked spleen atrophy and B-cell lymphopenia were constantly observed (3). Therefore, we investigated vaccinal and anti-infectious responses of Ghrh-/- mice against S.pneumoniae, a T-independent pathogen. Results. Transgenic mice were unable to trigger production of specific IgM after vaccination with either native pneumococcal polysaccharides (PPS, Pnx23) or protein-PPS conjugate (Prev13). GH treatment of Ghrh-/- mice restored IgM response to Pnx23 vaccine but not to Prev13 suggesting that GH exerts a significant impact on the spleen marginal zone that is strongly implicated in T-independent immunological response to pneumococcal polysaccharides. After intranasal instillation of a non-lethal dose of S.pneumoniae, Ghrh-/- mice exhibited a dramatic susceptibility with a time-dependent increase in lung bacterial load, a bacteremia already after 24h, and a survival limit of 48-72h. In marked contrast, WT and heterozygote mice completely cleared S.pneumoniae infection after 24h. Lungs of infected Ghrh-/- mice were massively infiltrated by inflammatory macrophages, while lung B cells were markedly decreased. Transcription of Ifng, Il10, Cd40, and Cxcl9 was highly increased in the lungs of infected Ghrh-/- mice, whereas Tgfb and Iggj transcripts were unchanged. Resistance of Ghrh-/- mice to infection by influenzavirus H1N1 (a T-dependent antigen) was normal or slightly decreased. Conclusion. This animal model shows that the somatotrope GHRH/GH/IGF1 axis plays a vital and unsuspected role in the vaccine and immunological defense against S.pneumoniae. [less ▲]

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See detailLong-term use of darunavir/ritonavir-containing regimens in daily practice in Belgium: retrospective observational cohort data of 1701 HIV-patients
De Wit, S.; Florence, Eric ULiege; Vandekerckhove, L. et al

in Acta Clinica Belgica (2018)

Background: Once daily (QD) ritonavir or cobicistat-boosted darunavir (DRV/b), in combination with other antiretrovirals (ARVs), is recommended as a first-line option for human immunodeficiency virus ... [more ▼]

Background: Once daily (QD) ritonavir or cobicistat-boosted darunavir (DRV/b), in combination with other antiretrovirals (ARVs), is recommended as a first-line option for human immunodeficiency virus-infected patients in European and USA guidelines. The objective of this study was to analyse the outcomes of DRV/r QD-based antiretroviral therapy (ART) regimens in real-life settings. Methods: This is an observational, non-interventional, non-comparative, retrospective, multicentre cohort study. Data were collected from the databases of eight Belgian AIDS Reference Centres. All patients who received at least one dose of DRV/r QD, regardless of background ARV regimen, with a minimum follow-up of 6 months were included. Results: Data from 1701 subjects were collected. Most were male (66.5%) with a mean age of 42.9 years, 33.1% were treatment-naïve and 66.9% were ART experienced. During a median follow-up of 2.45 years (95% CI: 1.50–3.34), the probability to remain on treatment was 87% for the first year, 79% for the second year. DRV/r was well tolerated with few discontinuations due to adverse events (6.9%) or virological failure (0.8%). Among the 1138 treatment-experienced patients, 111 (9.8%) patients received DRV/r QD monotherapy. Conclusions: This retrospective cohort analysis confirms the long-term effectiveness and good tolerability of DRV/r QD in a real-life setting. No unexpected adverse events were reported. © Acta Clinica Belgica 2018 [less ▲]

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See detailCanakinumab for the Treatment of Autoinflammatory Recurrent Fever Syndromes.
De Benedetti, Fabrizio; Gattorno, Marco; Anton, Jordi et al

in New England Journal of Medicine (2018), 378(20), 1908-1919

BACKGROUND: Familial Mediterranean fever, mevalonate kinase deficiency (also known as the hyperimmunoglobulinemia D syndrome), and the tumor necrosis factor receptor-associated periodic syndrome (TRAPS ... [more ▼]

BACKGROUND: Familial Mediterranean fever, mevalonate kinase deficiency (also known as the hyperimmunoglobulinemia D syndrome), and the tumor necrosis factor receptor-associated periodic syndrome (TRAPS) are monogenic autoinflammatory diseases characterized by recurrent fever flares. METHODS: We randomly assigned patients with genetically confirmed colchicine-resistant familial Mediterranean fever, mevalonate kinase deficiency, or TRAPS at the time of a flare to receive 150 mg of canakinumab subcutaneously or placebo every 4 weeks. Patients who did not have a resolution of their flare received an add-on injection of 150 mg of canakinumab. The primary outcome was complete response (resolution of flare and no flare until week 16). In the subsequent phase up to week 40, patients who had a complete response underwent a second randomization to receive canakinumab or placebo every 8 weeks. Patients who underwent a second randomization and had a subsequent flare and all other patients received open-label canakinumab. RESULTS: At week 16, significantly more patients receiving canakinumab had a complete response than those receiving placebo: 61% vs. 6% of patients with colchicine-resistant familial Mediterranean fever (P<0.001), 35% versus 6% of those with mevalonate kinase deficiency (P=0.003), and 45% versus 8% of those with TRAPS (P=0.006). The inclusion of patients whose dose was increased to 300 mg every 4 weeks yielded a complete response in 71% of those with colchicine-resistant familial Mediterranean fever, 57% of those with mevalonate kinase deficiency, and 73% of those with TRAPS. After week 16, an extended dosing regimen (every 8 weeks) maintained disease control in 46% of patients with colchicine-resistant familial Mediterranean fever, 23% of those with mevalonate kinase deficiency, and 53% of those with TRAPS. Among patients who received canakinumab, the most frequently reported adverse events were infections (173.3, 313.5, and 148.0 per 100 patient-years among patients with colchicine-resistant familial Mediterranean fever, those with mevalonate kinase deficiency, and those with TRAPS, respectively), with a few being serious infections (6.6, 13.7, and 0.0 per 100 patient-years). CONCLUSIONS: In this trial, canakinumab was effective in controlling and preventing flares in patients with colchicine-resistant familial Mediterranean fever, mevalonate kinase deficiency, and TRAPS. (Funded by Novartis; CLUSTER ClinicalTrials.gov number, NCT02059291 .). [less ▲]

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See detailPhenotype, penetrance, and treatment of 133 cytotoxic T-lymphocyte antigen 4-insufficient subjects.
Schwab, Charlotte; Gabrysch, Annemarie; Olbrich, Peter et al

in Journal of Allergy and Clinical Immunology (2018), 142(6), 1932-1946

BACKGROUND: Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is a negative immune regulator. Heterozygous CTLA4 germline mutations can cause a complex immune dysregulation syndrome in human subjects. OBJECTIVE ... [more ▼]

BACKGROUND: Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is a negative immune regulator. Heterozygous CTLA4 germline mutations can cause a complex immune dysregulation syndrome in human subjects. OBJECTIVE: We sought to characterize the penetrance, clinical features, and best treatment options in 133 CTLA4 mutation carriers. METHODS: Genetics, clinical features, laboratory values, and outcomes of treatment options were assessed in a worldwide cohort of CTLA4 mutation carriers. RESULTS: We identified 133 subjects from 54 unrelated families carrying 45 different heterozygous CTLA4 mutations, including 28 previously undescribed mutations. Ninety mutation carriers were considered affected, suggesting a clinical penetrance of at least 67%; median age of onset was 11 years, and the mortality rate within affected mutation carriers was 16% (n = 15). Main clinical manifestations included hypogammaglobulinemia (84%), lymphoproliferation (73%), autoimmune cytopenia (62%), and respiratory (68%), gastrointestinal (59%), or neurological features (29%). Eight affected mutation carriers had lymphoma, and 3 had gastric cancer. An EBV association was found in 6 patients with malignancies. CTLA4 mutations were associated with lymphopenia and decreased T-, B-, and natural killer (NK) cell counts. Successful targeted therapies included application of CTLA-4 fusion proteins, mechanistic target of rapamycin inhibitors, and hematopoietic stem cell transplantation. EBV reactivation occurred in 2 affected mutation carriers after immunosuppression. CONCLUSIONS: Affected mutation carriers with CTLA-4 insufficiency can present in any medical specialty. Family members should be counseled because disease manifestation can occur as late as 50 years of age. EBV- and cytomegalovirus-associated complications must be closely monitored. Treatment interventions should be coordinated in clinical trials. [less ▲]

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See detailSystemic AA Amyloidosis Caused by Inflammatory Hepatocellular Adenoma.
Calderaro, Julien; Letouze, Eric; Bayard, Quentin et al

in New England Journal of Medicine (2018), 379(12), 1178-1180

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See detailA case of giant cell arteritis associated with culture-proven Coxiella burnetii aortitis
de Worm, S.; GIOT, Jean-Baptiste ULiege; Courtoy, C. et al

in International Journal of Infectious Diseases (2018), 69

A case of proven Coxiella burnetii aortitis, possibly associated with giant cell arteritis (GCA), is reported. A 72-year-old man, who is a hunter, presented with weight loss, fever, jaw claudication, and ... [more ▼]

A case of proven Coxiella burnetii aortitis, possibly associated with giant cell arteritis (GCA), is reported. A 72-year-old man, who is a hunter, presented with weight loss, fever, jaw claudication, and hardened temporal arteries associated with a persistent inflammatory syndrome and arteritis of the whole aorta, including the brachiocephalic arteries, as seen on 18F-fluorodeoxyglucose positron emission tomography/computed tomography. The diagnosis of GCA was retained, and treatment with prednisolone was started. Given the aneurysm of the abdominal aorta, the patient underwent replacement of the abdominal aorta with an allograft. Histology showed intense chronic arteritis attributed to atherosclerosis with dissection. However, Coxiella burnetii infection was confirmed by serology and then by culture and molecular biology on the surgical specimen. A combination of hydroxychloroquine and doxycycline was added to tapered prednisolone and the outcome was favourable. © 2018 The Author(s) [less ▲]

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See detailIncreased risk for malignancies in 131 affected CTLA4 mutation carriers
Egg, D.; Schwab, C.; Gabrysch, A. et al

in Frontiers in Immunology (2018), 9(SEP),

Background: Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is a negative immune regulator on the surface of T cells. In humans, heterozygous germline mutations in CTLA4 can cause an immune ... [more ▼]

Background: Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is a negative immune regulator on the surface of T cells. In humans, heterozygous germline mutations in CTLA4 can cause an immune dysregulation syndrome. The phenotype comprises a broad spectrum of autoinflammatory, autoimmune, and immunodeficient features. An increased frequency of malignancies in primary immunodeficiencies is known, but their incidence in CTLA-4 insufficiency is unknown. Methods: Clinical manifestations and details of the clinical history were assessed in a worldwide cohort of 184 CTLA4 mutation carriers. Whenever a malignancy was reported, a malignancy-specific questionnaire was filled. Results: Among the 184 CTLA4 mutation carriers, 131 were considered affected, indicating a penetrance of 71.2%. We documented 17 malignancies, which amounts to a cancer prevalence of 12.9% in affected CTLA4 mutation carriers. There were ten lymphomas, five gastric cancers, one multiple myeloma, and one metastatic melanoma. Seven lymphomas and three gastric cancers were EBV-associated. Conclusion: Our findings demonstrate an elevated cancer risk for patients with CTLA-4 insufficiency. As more than half of the cancers were EBV-associated, the failure to control oncogenic viruses seems to be part of the CTLA-4-insufficient phenotype. Hence, lymphoproliferation and EBV viral load in blood should be carefully monitored, especially when immunosuppressing affected CTLA4 mutation carriers. © 2018 Egg, Schwab, Gabrysch, Arkwright, Cheesman, Giulino-Roth, Neth, Snapper, Okada, Moutschen, Delvenne, Pecher, Wolff, Kim, Seneviratne, Kim, Kang, Ojaimi, McLean, Warnatz, Seidl and Grimbacher. [less ▲]

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See detailWild-type HIV infection despite PrEP: a lot to learn from a case report.
DARCIS, Gilles ULiege; Moutschen, Michel ULiege

in Lancet HIV (2018), 5(1), 10

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See detailImmunosenescence and infectious diseases
Moutschen, Michel ULiege; Martens, Henri ULiege; Geenen, Vincent ULiege

in Michel, Jean-Pierre; Beattie, B. Lynn; Martin, Finbarr C. (Eds.) et al Oxford Textbook of Geriatric Medicine - 3rd Edition (2017)

In this chapter, we will briefly review the principal modes of interactions taking place between the host’s immune system and the principal groups of microorganisms. We will focus on the way these modes ... [more ▼]

In this chapter, we will briefly review the principal modes of interactions taking place between the host’s immune system and the principal groups of microorganisms. We will focus on the way these modes of interactions are modified by intrinsic and extrinsic factors associated with ageing. As described in Chapter 45, one of the principal features of immunosenescence is linked to thymus involution with subsequent loss of diversity of the repertoire of naïve T-cells. This has a major impact on the adaptative immune responses developed against newly encountered pathogens. Interestingly, more ubiquitous mechanisms associated with the ageing process itself could also have an impact on innate immunity. Defective autophagy impairs the clearance of intracellular pathogens and age-related defects of the ubiquitination-proteasome pathway concur to blunt antiviral responses. In summary, healthy ageing is associated with subtle impairments of innate and adaptive immunity directed against all groups of pathogens. The presence of comorbid states often exerts a synergistic effect on the susceptibility to infectious diseases. [less ▲]

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See detailExploring the link between innate immune activation and thymic function by measuring sCD14 and TRECs in HIV patients living in Belgium
DE VOEGHT, Adrien ULiege; Martens, Henri ULiege; RENARD, Jeanne de Chantal ULiege et al

in PLoS ONE (2017)

Microbial translocation is now viewed as a central event in the pathogenesis of chronic inflammation during HIV infection. Thymic function failure is another crucial factor involved in HIV disease ... [more ▼]

Microbial translocation is now viewed as a central event in the pathogenesis of chronic inflammation during HIV infection. Thymic function failure is another crucial factor involved in HIV disease progression. The goal of this study was to explore the hypothesis of potential links between microbial translocation and thymic function in HIV-1 patients living in Belgium. The extent of microbial translocation was assessed through the measurement of soluble CD14 (sCD14). T-cell receptor excision circles (sjTRECs and dβTRECs) were used as a measure of thymic function. Data were collected from 75 HIV-infected patients. Simple and complex linear regressions were done to analyze the link between these two processes. We found a statistically relevant negative correlation between thymopoiesis (sjTREC) and sCD14 level (p = 0.004). These results suggest a link between thymic function failure, microbial translocation and innate immune activation. [less ▲]

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See detailDusp3 deletion in mice promotes experimental lung tumour metastasis in a macrophage dependent manner
Vandereyken, Maud; Jacques, Sophie ULiege; Van Overmeire, Eva et al

in PLoS ONE (2017)

Vaccinia-H1 Related (VHR) dual-specificity phosphatase, or DUSP3, plays an important role in cell cycle regulation and its expression is altered in several human cancers. In mouse model, DUSP3 deletion ... [more ▼]

Vaccinia-H1 Related (VHR) dual-specificity phosphatase, or DUSP3, plays an important role in cell cycle regulation and its expression is altered in several human cancers. In mouse model, DUSP3 deletion prevents neo-angiogenesis and b-FGF-induced microvessel out- growth. Considering the importance of angiogenesis in metastasis formation, our study aimed to investigate the role of DUSP3 in tumour cell dissemination. Using a Lewis Lung carcinoma (LLC) experimental metastasis model, we observed that DUSP3-/- mice devel- oped larger lung metastases than littermate controls. DUSP3-/- bone marrow transfer to lethally irradiated DUSP3+/+ mice was sufficient to transfer the phenotype to DUSP3+/+ mice, indicating that hematopoietic cells compartment was involved in the increased tumour cell dissemination to lung tissues. Interestingly, we found a higher percentage of tumour- promoting Ly6Cint macrophages in DUSP3-/- LLC-bearing lung homogenates that was at least partially due to a better recruitment of these cells. This was confirmed by 1) the pres- ence of higher number of the Ly6Bhi macrophages in DUSP3-/- lung homogenates and by 2) the better migration of DUSP3-/- bone marrow sorted monocytes, peritoneal macrophages and bone marrow derived macrophages (BMDMs), compared to DUSP3+/+ monocytes, macrophages and BMDMs, in response to LLC-conditioned medium. Our study demon- strates that DUSP3 phosphatase plays a key role in metastatic growth through a mechanism involving the recruitment of macrophages towards LLC-bearing lungs. [less ▲]

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See detailRecurrence of visceral and muco-cutaneous leishmaniasis in a patient under immunosuppressive therapy
DARCIS, Gilles ULiege; Van der Auwera, Gert; GIOT, Jean-Baptiste ULiege et al

in BMC Infectious Diseases (2017), 17

Background: Leishmaniasis is a protozoan disease caused by parasites of the genus Leishmania, transmitted to humans by sandflies. The diagnosis of leishmaniasis is often challenging as it mimics many ... [more ▼]

Background: Leishmaniasis is a protozoan disease caused by parasites of the genus Leishmania, transmitted to humans by sandflies. The diagnosis of leishmaniasis is often challenging as it mimics many other infectious or alignant diseases. The disease can present in three ways: cutaneous, mucocutaneous, or visceral leishmaniasis, which rarely occur together or consecutively. Case presentation: The patient was a 52 years old immunosuppressed Belgian woman with a long history of severe rheumatoid arthritis. She underwent bone marrow biopsy to explore thrombocytopenia. Diagnosis of visceral leishmaniasis was made by identification of Leishman Donovan (LD) bodies in macrophages. Treatment with liposomal amphotericin B was successful. She later developed cutaneous leishmaniasis treated with amphotericin B lipid complex. She next presented with relapsing cutaneous lesions followed by rapidly progressing lymphadenopathies. Biopsy confirmed the diagnosis of leishmaniasis. Treatments by miltefosine, amphotericin B, N-methyl-glucamine antimoniate were subsequently initiated. She later presented a recurrent bone marrow involvement treated with intramuscular paromomycin and miltefosine. She died two years later from leukemia. At the time of death, she presented with a mucosal destruction of the nose. A Leishmania-specific PCR (Polymerase Chain Reaction) identified L. infantum as etiological agent. Conclusions: Clinicians should be aware of the potential concomitant or sequential involvement of multiple anatomic localizations of Leishmania in immunosuppressed patients. [less ▲]

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See detailA surprising and dramatic neuroendocrine-immune phenotype of mice deficient in Growth Hormone-Releasing Hormone (GHRH)
Farhat, Khalil; Bodart, Gwennaëlle ULiege; RENARD, Jeanne de Chantal ULiege et al

Poster (2017, May 23)

In the framework of close interactions between the immune and neuroendocrine systems, Growth Hormone (GH) has been proposed to exert significant effects on the immune system, but there is not yet a ... [more ▼]

In the framework of close interactions between the immune and neuroendocrine systems, Growth Hormone (GH) has been proposed to exert significant effects on the immune system, but there is not yet a consensus about GH immunomodulatory properties. These studies investigated the immune and anti-infectious response of dwarf Ghrh-/- mice presenting a severe deficiency of the GHRH/GH/IGF-1 axis. In basal conditions, thymic parameters and T-cell responses of Ghrh-/- mice were not severely affected but a constant B-cell lymphopaenia was observed. Thus, we investigated vaccine and anti-infectious responses of Ghrh-/- mice toward Streptococcus pneumonia, a B-dependent pathogen, Ghrh-/- mice were unable to trigger production of specific IgM and IgG against serotype 1 pneumococcal polysaccharide (PPS) after vaccination with either native PPS (Pnx23) or protein-PPS conjugate (Prev-13) vaccines. These vaccines both include the serotype 1 (our S.pneumoniae strain) and provide an effective protection in mice. A short GH supplementation to Ghrh-/- mice (1 daily injection of 1 mg/kg GH for 4 weeks) restored IgM and IgG response to Pnx23 vaccine but not to Prev-13. This suggests that GH could exert distinct impacts upon spenic areas. Furthermore, after intranasal instillation of a non-lethal dose (defined by the full clearance by WT C57BL/6 mice after 24h) of serotype 1 S.pneumoniae, Ghrh-/- mice exhibited a dramatic susceptibility. This was proved by a marked time-dependent increase in pulmonary bacterial, a septicemia already 24h after infection and a survival limit of 72h. We also observed a dramatic decrease in lung B- and T-cell populations and an increase in proportion of inflammatory macrophages. By contrast, wild-type and heterozygote mice completely cleared S.pneumoniae infection after 24h. In conclusion, our data show without ambiguity that the somatotrope GHRH/GH/IGF-1 axis plays an important and unsuspected role in defense against S.Pneumoniae. [less ▲]

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See detailA surprising and dramatic neuroendocrine-immune phenotype of mice deficient in Growth Hormone-Releasing Hormone (GHRH)
Farhat, Khalil ULiege; Bodart, Gwennaëlle ULiege; Renard, chantal et al

Poster (2017, May)

In the framework of close interactions between the immune and neuroendocrine systems, Growth Hormone (GH) has been proposed to exert significant effects on the immune system, but there is not yet a ... [more ▼]

In the framework of close interactions between the immune and neuroendocrine systems, Growth Hormone (GH) has been proposed to exert significant effects on the immune system, but there is not yet a consensus about GH immunomodulatory properties. These studies investigated the immune and anti-infectious response of dwarf Ghrh-/- mice presenting a severe deficiency of the GHRH/GH/IGF-1 axis. In basal conditions, thymic parameters and T-cell responses of Ghrh-/- mice were not severely affected but a constant B-cell lymphopaenia was observed. Thus, we investigated vaccine and anti-infectious responses of Ghrh-/- mice toward Streptococcus pneumonia, a B-dependent pathogen, Ghrh-/- mice were unable to trigger production of specific IgM and IgG against serotype 1 pneumococcal polysaccharide (PPS) after vaccination with either native PPS (Pnx23) or protein-PPS conjugate (Prev-13) vaccines. These vaccines both include the serotype 1 (our S.pneumoniae strain) and provide an effective protection in mice. A short GH supplementation to Ghrh-/- mice (1 daily injection of 1 mg/kg GH for 4 weeks) restored IgM and IgG response to Pnx23 vaccine but not to Prev-13. This suggests that GH could exert distinct impacts upon spenic areas. Furthermore, after intranasal instillation of a non-lethal dose (defined by the full clearance by WT C57BL/6 mice after 24h) of serotype 1 S.pneumoniae, Ghrh-/- mice exhibited a dramatic susceptibility. This was proved by a marked time-dependent increase in pulmonary bacterial, a septicemia already 24h after infection and a survival limit of 72h. We also observed a dramatic decrease in lung B- and T-cell populations and an increase in proportion of inflammatory macrophages. By contrast, wild-type and heterozygote mice completely cleared S.pneumoniae infection after 24h. In conclusion, our data show without ambiguity that the somatotrope GHRH/GH/IGF-1 axis plays an important and unsuspected role in defense against S.Pneumoniae. [less ▲]

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See detailIgG4-related membranous glomerulonephritis and generalized lymphadenopathy without pancreatitis: a case report
HUART, Justine ULiege; GROSCH, Stéphanie ULiege; BOVY, Christophe ULiege et al

in BMC Nephrology (2017), 18

Abstract Background: IgG4-related disease is a recently described pathologic entity. This is the case of a patient with nephrotic syndrome and lymphadenopathy due to IgG4-related disease. Such a kidney ... [more ▼]

Abstract Background: IgG4-related disease is a recently described pathologic entity. This is the case of a patient with nephrotic syndrome and lymphadenopathy due to IgG4-related disease. Such a kidney involvement is quite peculiar and has only been described a few times recently. Renal biopsy showed a glomerular involvement with membranous glomerulonephritis in association with a tubulo-interstitial nephropathy. Moreover, the patient was not suffering from pancreatitis. Case presentation: The patient is a middle-aged man of Moroccan origin. He has developed recurrent episodes of diffuse lymphadenopathies, renal failure and nephrotic syndrome. Renal biopsies showed membranous glomerulonephritis. Discussion and conclusion: The diagnostic approach of this atypical presentation is discussed in this case report as well as diagnostic criteria, therapeutic strategies, biomarkers and pathophysiology of IgG4-related disease. IgG4-related membranous glomerulonephritis is a well-established cause of membranous glomerulonephritis. It must be sought after in every patient with a previous diagnosis of IgG4-related disease and in every patient with this histological finding on renal biopsy. Corticoids are still the first-line treatment of IgG4-related disease. New therapeutic strategies are needed to avoid glucocorticoids long term side-effects. Interestingly, the patient was prescribed cyclophosphamide in addition to glucocorticoids for an immune thrombocytopenia. This treatment had a very good impact on his IgG4-related disease. [less ▲]

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See detailEndocardite à aggregatibacter aphrophilus sur prothèses valvulaires
Deleixhe, Benjamin ULiege; FRIPPIAT, Frédéric ULiege; Léonard, Philippe ULiege et al

in Revue Médicale de Liège (2017), 72(12), 522-528

We present the case of an acute endocarditis of mitral and aortic prosthetic heart valves caused by Aggregatibacter aphrophilus (Haemophilus aphrophilus-paraphrophilus). This third report in the ... [more ▼]

We present the case of an acute endocarditis of mitral and aortic prosthetic heart valves caused by Aggregatibacter aphrophilus (Haemophilus aphrophilus-paraphrophilus). This third report in the literature emphasizes the diagnostic work-up and the role of positron emission tomography combined with computed tomography in this setting. The specificities of endocarditis due to the HACEK group (Haemophilus spp., Aggregatibacter, Cardiobacterium hominis, Eikenella corrodens and Kingella spp.) and the specific microbiological data and therapeutic options pertinent to this germ are discussed. [less ▲]

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