Urinary lipoarabinomannan as predictor for the tuberculosis immune reconstitution inflammatory syndrome

info:eu-repo/semantics/published

Apparent treatment-resistant hypertension and chronic kidney disease: another cardiovascular-renal syndrome?

To identify patients at increased risk of cardiovascular (CV) outcomes, apparent treatment-resistant hypertension (aTRH) is defined as having a blood pressure above goal despite the use of 3 or more antihypertensive therapies of different classes at maximally tolerated doses, ideally including a diuretic. Recent epidemiologic studies in selected populations estimated the prevalence of aTRH as 10% to 15% among patients with hypertension and that aTRH is associated with elevated risk of CV and renal outcomes. Additionally, aTRH and CKD are associated. Although the pathogenesis of aTRH is multifactorial, the kidney is believed to play a significant role. Increased volume expansion, aldosterone concentration, mineralocorticoid receptor activity, arterial stiffness, and sympathetic nervous system activity are central to the pathogenesis of aTRH and are targets of therapies. Although diuretics form the basis of therapy in aTRH, pathophysiologic and clinical data suggest an important role for aldosterone antagonism. Interventional techniques, such as renal denervation and carotid baroreceptor activation, modulate the sympathetic nervous system and are currently in phase III trials for the treatment of aTRH. These technologies are as yet unproven and have not been investigated in relationship to CV outcomes or in patients with CKD.

Two Cases of Late Shone Syndrome With Pulmonary Hypertension: Heart-Lung Transplant or Valve Surgery?

Two cases of Shone syndrome with severe mitral and aortic valve problems and pulmonary hypertension were referred for heart-lung transplantation. Severely elevated pulmonary vascular resistance (PVR) was confirmed as was severe periprosthetic mitral and aortic regurgitation. Based on the severity of the valve lesions in both patients, surgery was decided upon and undertaken. Both experienced early pulmonary hypertensive crises, one more than the other, that gradually subsided, followed by excellent recovery and reversal of pulmonary hypertension and PVR. These cases illustrate Braunwald's concept that pulmonary hypertension secondary to left-sided valve disease is reversible.

Dominant Splice Site Mutations in PIK3R1 Cause Hyper IgM Syndrome, Lymphadenopathy and Short Stature.

The purpose of this research was to use next generation sequencing to identify mutations in patients with primary immunodeficiency diseases whose pathogenic gene mutations had not been identified. Remarkably, four unrelated patients were found by next generation sequencing to have the same heterozygous mutation in an essential donor splice site of PIK3R1 (NM_181523.2:c.1425 + 1G > A) found in three prior reports. All four had the Hyper IgM syndrome, lymphadenopathy and short stature, and one also had SHORT syndrome. They were investigated with in vitro immune studies, RT-PCR, and immunoblotting studies of the mutation's effect on mTOR pathway signaling. All patients had very low percentages of memory B cells and class-switched memory B cells and reduced numbers of naïve CD4+ and CD8+ T cells. RT-PCR confirmed the presence of both an abnormal 273 base-pair (bp) size and a normal 399 bp size band in the patient and only the normal band was present in the parents. Following anti-CD40 stimulation, patient's EBV-B cells displayed higher levels of S6 phosphorylation (mTOR complex 1 dependent event), Akt phosphorylation at serine 473 (mTOR complex 2 dependent event), and Akt phosphorylation at threonine 308 (PI3K/PDK1 dependent event) than controls, suggesting elevated mTOR signaling downstream of CD40. These observations suggest that amino acids 435-474 in PIK3R1 are important for its stability and also its ability to restrain PI3K activity. Deletion of Exon 11 leads to constitutive activation of PI3K signaling. This is the first report of this mutation and immunologic abnormalities in SHORT syndrome.

Acquired epidermodysplasia verruciformis syndrome in HIV-infected pediatric patients: Prospective treatment trial with topical glycolic acid and human papillomavirus genotype characterization

SCOPUS: ar.j

Incidence and predictors of mortality and the effect of tuberculosis immune reconstitution inflammatory syndrome in a cohort of TB/HIV patients commencing antiretroviral therapy.

info:eu-repo/semantics/published

Syndrome d'immunodéficience acquise (AIDS) révélé par un herpes génital sévère. A propos de deux cas.

The authors present 2 cases of AIDS revealed by severe recurrent genital herpes simplex. The patients are 2 young, previously healthy, African women without histories of homosexuality or drug abuse. The first patient died after 5 months of follow-up (post mortem findings: viral bronchopneumonia with positive cultures for herpes and cytomegalovirus (CMV), viral colitis due to CMV). The second patient survived. She has been treated, during the last 11 months, for filariasis, buccal and vaginal candidiasis and cerebral toxoplasmosis.

LPS-binding protein and IL-6 Mark paradoxical tuberculosis immune reconstitution inflammatory syndrome in HIV patients

Background: Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) remains a poorly understood complication in HIV-TB co-infected patients initiating antiretroviral therapy (ART). The role of the innate immune system in TB-IRIS is becoming increasingly apparent, however the potential involvement in TB-IRIS of a leaky gut and proteins that interfere with TLR stimulation by binding PAMPs has not been investigated before. Here we aimed to investigate the innate nature of the cytokine response in TB-IRIS and to identify novel potential biomarkers. Methods: From a large prospective cohort of HIV-TB co-infected patients receiving TB treatment, we compared 40 patients who developed TB-IRIS during the first month of ART with 40 patients matched for age, sex and baseline CD4 count who did not. We analyzed plasma levels of lipopolysaccharide (LPS)-binding protein (LBP), LPS, sCD14, endotoxin-core antibody, intestinal fatty acid-binding protein (I-FABP) and 18 pro-and anti-inflammatory cytokines before and during ART. Results: We observed lower baseline levels of IL-6 (p = 0.041), GCSF (p = 0.036) and LBP (p = 0.016) in TB-IRIS patients. At IRIS event, we detected higher levels of LBP, IL-1RA, IL-4, IL-6, IL-7, IL-8, G-CSF (p ≤ 0.032) and lower I-FABP levels (p = 0.013) compared to HIV-TB co-infected controls. Only IL-6 showed an independent effect in multivariate models containing significant cytokines from pre-ART (p = 0.039) and during TB-IRIS (p = 0.034). Conclusion: We report pre-ART IL-6 and LBP levels as well as IL-6, LBP and I-FABP levels during IRIS-event as potential biomarkers in TB-IRIS. Our results show no evidence of the possible contribution of a leaky gut to TB-IRIS and indicate that IL-6 holds a distinct role in the disturbed innate cytokine profile before and during TB-IRIS. Future clinical studies should investigate the importance and clinical relevance of these markers for the diagnosis and treatment of TB-IRIS. Copyright: © 2013 Goovaerts et al.

Helper T cell dysfunctions in a patient with Omenn's syndrome: modulation by IFN-gamma therapy.

Case Reports

Antibody-deficiency and Acute Nephritic Syndrome in a Patient with Homozygous Disruption of the CD81 Gene

info:eu-repo/semantics/nonPublished

Antibody-deficiency and Acute Nephritic Syndrome in a Patient with Homozygous Disruption of the CD81 Gene

info:eu-repo/semantics/nonPublished

Clinical Spectrum, risk factors and outcome of immune reconstitution inflammatory syndrome in patients with tuberculosis-HIV coinfection.

info:eu-repo/semantics/published

Contribution à l'étude de la réponse de type IgA chez l'homme: signification de la présence des anticorps IgA polymériques

Doctorat en sciences médicales

Modulation of the complement system in monocytes contributes to tuberculosis-associated immune reconstitution inflammatory syndrome.

Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a common complication in HIV-TB co-infected patients receiving combined antiretroviral therapy (cART). This study investigated a putative contribution of monocytes to the development of TB-IRIS.