S. Fellahi

Increased systemic immune activation and inflammatory profile of long-term HIV-infected ART-controlled patients is related to personal factors, but not to markers of HIV infection severity

OBJECTIVESnThe objective of this study was to analyse the respective roles of personal factors and HIV infection markers on the systemic immune activation/inflammatory profile of long-term antiretroviral treatment-controlled patients.nnnPATIENTS AND METHODSnA panel of soluble immune activation/inflammatory biomarkers was measured in 352 HIV-infected treatment-controlled patients from the APROCO-COPILOTE cohort, all of whom were started on a PI in 1997-99 and had a final evaluation 11 years later, and in 59 healthy controls.nnnRESULTSnA total of 81.5% of the patients were male, with the following characteristics: median age 49 years; 620 CD4 cells/mm(3); 756 CD8 cells/mm(3); CD4/CD8 ratio 0.81; BMI 23.0 kg/m(2); waist-to-hip ratio 0.95. Markers of inflammation-high-sensitivity (hs) IL-6 (median and IQR) (1.3 pg/L, 0.7-2.6), hs C-reactive protein (CRP) (2.1 mg/L, 0.9-4.5) and D-dimer (252 ng/mL, 177-374)-were elevated compared with healthy controls (Pu200a<u200a0.001) and strongly related to each other, as were markers of immune activation [soluble (s) CD14 (1356 ng/mL, 1027-1818), β2-microglobulin (2.4 mg/L, 2.0-3.1) and cystatin-C (0.93 mg/L, 0.82-1.1)]. Inflammatory and immune activation markers were also associated with each other. In HIV-infected patients: age was related to D-dimer, β2-microglobulin and cystatin-C levels; being a smoker was related to increased IL-6 and cystatin-C; and BMI and waist-to-hip ratio were related to CRP. Conversely, markers of HIV infection, current CD4 or CD8 values, CD4 nadir, CD4/CD8 ratio, AIDS stage at initiation of PIs, current viral load and duration of ART were not associated with immune activation/inflammation markers.nnnCONCLUSIONSnIn these long-term treatment-controlled HIV-infected patients, all systemic markers of inflammation and immune activation were increased compared with healthy controls. This was related to demographic and behavioural factors, but not to markers of severity of the HIV infection. Intervention to decrease low-grade inflammation must thus prioritize modifiable personal factors.

Late Antiretroviral Therapy (ART) Initiation Is Associated with Long-Term Persistence of Systemic Inflammation and Metabolic Abnormalities.

Objectives HIV-induced immunodeficiency is associated with metabolic abnormalities and systemic inflammation. We investigated the effect of antiretroviral therapy (ART) on restoration of insulin sensitivity, markers of immune activation and inflammation. Methods Immunological, metabolic and inflammatory status was assessed at antiretroviral therapy initiation and three years later in 208 patients from the ANRS-COPANA cohort. Patients were compared according to their pre-ART CD4+ cell count (group 1: ≤ 200/mm3, n = 66 vs. group 2: > 200/mm3, n = 142). Results Median CD4+ cell count increased in both groups after 3 years of successful ART but remained significantly lower in group 1 than in group 2 (404 vs 572 cells/mm3). Triglyceride and insulin levels were higher or tended to be higher in group 1 than in group 2 at ART initiation (median: 1.32 vs 0.97 mmol/l, p = 0.04 and 7.6 vs 6.8 IU, p = 0.09, respectively) and remained higher after three years of ART (1.42 vs 1.16 mmol/L, p = 0.0009 and 8.9 vs 7.2 IU, p = 0.01). After adjustment for individual characteristics and antiretroviral therapy regimens (protease inhibitor (PI), zidovudine), insulin levels remained significantly higher in patients with low baseline CD4+ cell count. Baseline IL-6, sCD14 and sTNFR2 levels were higher in group 1 than in group 2. Most biomarkers of immune activation/inflammation declined during ART, but IL-6 and hsCRP levels remained higher in patients with low baseline CD4+ cell count than in the other patients (median are respectively 1.4 vs 1.1 pg/ml, p = 0.03 and 2.1 vs 1.3 mg/ml, p = 0.07). Conclusion After three years of successful ART, low pretreatment CD4+ T cell count remained associated with elevated insulin, triglyceride, IL-6 and hsCRP levels. These persistent metabolic and inflammatory abnormalities could contribute to an increased risk of cardiovascular and metabolic disease.

Concordance between CRP and SAA in familial Mediterranean fever during attack-free period: A study of 218 patients.

INTRODUCTIONnMonitoring SAA level in attack-free FMF patients is recommended in order to adjust colchicine dose, and minimize the risk of AA amyloidosis. In countries where this test is not available, C-reactive protein (CRP), another acute phase reactant, is used instead. However, CRP is low and SAA is increased in some patients and vice versa.nnnOBJECTIVESnTo determine the threshold of CRP corresponding to SAA<10mg/L in patients with FMF and to assess their concordance at the patient level.nnnPATIENTS AND METHODSnConsecutive FMF patients in attack-free period and no other cause of intermittent inflammation including infections were recruited during their regular visits in the French reference center for FMF. Demographic and genetic data were recorded; CRP and SAA were tested simultaneously. The threshold value of CRP corresponding to 10mg/L for SAA was determined and the concordance between the two markers was assessed with Cohens kappa index.nnnRESULTSn399 samples were obtained from 218 patients, mean age of 27years (33% under 18years old), 55% of female, from Sephardic Jewish origin in 71%. MEFV mutation was M694V homozygous or compound heterozygous in 52%, and simple heterozygous in 18%. Six patients had AA amyloidosis. The appropriate CRP threshold was found to be 5mg/L in children and 8.75mg/L in adults. Global agreement with SAA<10mg/L was 84% [95% confidence interval: 82 to 86%], leading to a kappa index at 0.62 [95% confidence interval: 0.57 to 0.68].nnnCONCLUSIONnCRP<5mg/L in FMF children or 8.75mg/L in FMF adults during attack-free periods might be a convenient substitute to guide therapeutic decisions when SAA is unavailable.

Adipokines in Semen: Physiopathology and Effects on Spermatozoas

Adipokines are secreted by adipose tissue and could be the link between obesity and infertility. Different studies investigated the involvement of adipokines in reproductive functions but only a few have looked into the male part. This review assesses adipokine functions on male reproductive parameters. Adiponectin seems to have a positive effect on sperm parameters, whereas other adipokines such as resistin or chemerin would have a rather deleterious effect on spermatogenesis. Semen parameters seem to be impacted when resistin and chemerin are increased: indeed, there is a decrease of sperm motility. Sperm morphology is improved when adiponectin is increased. The most studied adipokine, leptin, has a dual effect with a positive effect on sperm at physiological levels and a negative one for high seminal concentrations. Many semen parameters and fertility itself are disturbed according to semen adipokine levels, even if it is not the only interfering element. Taken together, adipokines are found in human and animal semen and most of them or their receptors are expressed in male genital tract. Although the pathophysiological role of adipokines in semen is not clearly elucidated, the adipokines could influence sperm functionality and could be potential biomarkers of male fertility.

Comparison of two techniques of adiponectin assay, ELISA and immunoturbidimetry: Should we move towards standardization?

Diabetes & Metabolism - In Press.Proof corrected by the author Available online since vendredi 13 janvier 2017

CA-010: Comparaison de deux techniques de dosage d'adiponectine (ELISA versus turbidimétrie) : faut-il aller vers une standardisation ?

Introduction Ladiponectine est une adipokine dont les proprietes biologiques multiples interviennent a plusieurs niveaux : metabolique, cardiovasculaire, osteo-articulaire, renal et dans les processus de carcinogenese. Son dosage immunologique fait le plus souvent appel aux techniques manuelles de type ELISA (Enzyme-Linked Immunosorbent Assays). Cependant, depuis quelques annees, ce dosage a ete developpe en immuno-turbidimetrie ce qui a permis son automatisation et dorenavant son accessibilite sur differents analyseurs de biochimie clinique. Patients et Methodes Comparer les resultats du dosage de ladiponectine totale realises en technique ELISA (Kit ALPCO) et en technique immuno-turbidimetrique (Kit RANDOX) sur analyseur Architect Ci8200 (ABBOTT) a partir dechantillons de serums issus dune cohorte de sujets ( n =439) ayant participe a une etude clinique financee par lANRS. Resultats Les resultats montraient une correlation significative entre les 2 tests (rho de Spearma n =0,861, p p vs 8,8mg/L (IQR 6,8-11,9) en immunoturbidimetrie. Apres reajustement des valeurs de calibrant RANDOX en fonction de leur dosage en ELISA avec le kit ALPCO, bien que toujours significati-vement differents ( p Conclusions Nos resultats montrent une excellente correlation entre les mesures dadiponectine totale mesurees manuellement en technique ELISA et automatiquement en immuno-turbidimetrie sur analyseur de biochimie. Neanmoins, les differences obtenues en donnees ponderales posent la question dune standardisation des techniques utilisees pour le dosage de ladiponectine, puisque plusieurs etudes recemment publiees proposent deja des valeurs usuelles de cette adipokine chez lenfant en fonction de lâge, du sexe et de la corpulence.

Hidradenitis suppurativa and familial Mediterranean fever: a report of 6 cases and literature review

Familial Mediterranean fever (FMF) is the most frequent monogenic autoinflammatory disease (AID). Hidradenitis suppurativa (HS) is an inflammatory skin disease characterized by recurrent abscesses and scarring in apocrine gland-bearing areas. HS shares common features with AID including a positive correlation between the increase of acute phase reactants (APR) and the severity of the disease. HS can be associated with other AID.

PW01-022 – Dissociation between CRP and SAA in FMF

An Israeli study previously showed that dissociation between normal C-reactive protein (CRP) and elevated serum amyloid A (SAA) could be observed in Familial Mediterranean fever (FMF). Considering that elevated SAA is predictive for AA amyloidosis, this study suggested that SAA could be a better tool in the diagnosis and therapeutic management of FMF.