La carga viral y células TCD4+ en pacientes infectados con el virus de inmunodeficiencia humana (VIH) coinfectados con sífilis / The viral load and TCD4+ cells in human immunodeficiency virus (HIV) infected patients coinfected with syphilis

La coinfección con sífilis en el paciente infectado con VIH-1 ha aumentado en los últimos años. La sífilis se ha asociado con activación inmunológica, pero el efecto de la misma sobre los parámetros inmunovirológicos en esta población aún son controversiales. El objetivo es evaluar el efecto de la sífilis en el contaje de células TCD4+ y la carga viral del paciente VIH+. Se realizó un estudio retrospectivo, multicéntrico, de casos y controles, extrayendo de las historias clínicas de los pacientes VIH+ que asistieron a control en los últimos 10 años, los reportes de contaje de células TCD4+ y carga viral, antes, durante y después del diagnóstico de sífilis para compararlos entre sí y con un grupo control. 48 pacientes VIH+ diagnosticados con sífilis conformaron el grupo de estudio y 56 sin sífilis, el grupo control. 14 (29%) pacientes con sífilis secundaria, 33 (69%) latente y 1 (2%) primaria. 38 (80%) recibían TARV en el momento de la sífilis. 24 (70%) elevaron sus valores de TCD4+ durante la enfermedad y 27(59%) posterior a ella, con una media de elevación de 19,41 celulas x mm³ (p=0,43) y 23,74 células x mm³ (p=0,28) respectivamente. Las determinaciones de carga viral se elevaron durante la enfermedad en 8 (38%) pacientes con una media de elevación de 64688 copias ARN-VIH/ml (4,96 log10) (p=0,03), y disminuyeron en 13 (45%) con una media de -1163 copias de ARN/ml (3,06 log10) (p=0,99) posteriormente. La sífilis en el paciente VIH+ estuvo asociada a elevaciones significativas en la carga viral y a cambios no significativos en el contaje de células TCD4+ durante la enfermedad.

Syphilis co-infection in HIV-1 patients has increased in recent years. Syphilis has been linked to immunoactivation, however, its effect on immunovirological parameters in this population is still controversial. Objective evaluate the effect of syphilis on the TCD4+ cell count andviral load of the HIV+ patient. A retrospective, multicenter case-control study was conducted by extracting the TCD4+ cell counts and viral load before, during, and after diagnosis of syphilis, from the clinical records of HIV+ patients who attended check-ups in the past 10 years, in order to compare them among themselves and against a control group. Seroprevalence of HIV/Syphilis co-infection was 18%. 48 HIV+ patients diagnosed with syphilis formed the study group, while 56, without syphilis, the control group. 14 (29%) had secondary, 33 (69%) latent and 1 (2%) primary syphilis. 38 (80%) received ART at the time of their syphilis. Of 24 (70%) the TCD4+ values increased during illness, and of 27 (59%) they increased subsequently, with a mean increase of 19.41 cell/mm³ (p=0.43) and 23.74 cell/mm³ (p=0.28) respectively. Measurements of the viral load increased in 8 (38%) patients during the disease with a mean increase of 64,688 HIV RNA copies/ml (4.96 log10) (p=0.03); and in 13 they decreased subsequently (45%) with a mean of -1,163 RNA copies/ml (3.06 log10) (p=0.99). Syphilis in the HIV+ patient was linked to significant increases in the viral load and to non-significant changes in the TCD4+ cell count during the disease.

Up regulated expression of fractalkine/CX3CL1 and CX3CR1 in patients with systemic sclerosis.

BACKGROUND: Fractalkine expressed on endothelial cells mediates activation and adhesion of leucocytes expressing its receptor, CX(3)CR1. Soluble fractalkine exhibits chemotactic activity for leucocytes expressing CX(3)CR1. OBJECTIVE: To determine the role of fractalkine and its receptor in systemic sclerosis (SSc) by assessing their expression levels in patients with this disease. METHODS: The expression of fractalkine and CX(3)CR1 in the skin and lung tissues was immunohistochemically examined. Circulating soluble fractalkine levels were examined by enzyme linked immunosorbent assay (ELISA). Blood samples from patients with SSc were stained for CX(3)CR1 with flow cytometric analysis. RESULTS: CX(3)CR1 levels on peripheral monocytes/macrophages and T cells were found to be raised in patients with diffuse cutaneous SSc. The numbers of cells expressing CX(3)CR1, including monocytes/macrophages, were increased in the lesional skin and lung tissues from patients with diffuse cutaneous SSc. Fractalkine was strongly expressed on endothelial cells in the affected skin and lung tissues. Soluble fractalkine levels were significantly raised in sera and were associated with raised erythrocyte sedimentation rates, digital ischaemia, and severity of pulmonary fibrosis. CONCLUSIONS: Up regulated expression of fractalkine and CX(3)CR1 cooperatively augments the recruitment of mononuclear cells expressing CX(3)CR1 into the affected tissue of SSc, leading to inflammation and vascular injury.

Novel role of the membrane-bound chemokine fractalkine in platelet activation and adhesion.

Chemokines released by the endothelium have proaggregatory properties on platelets. Fractalkine, a recently discovered membrane-bound chemokine with a transmembrane domain, is expressed in vascular injury; however, the effects of fractalkine on platelets have not yet been investigated. Blood was taken from healthy Wistar-Kyoto rats and the expression of the fractalkine receptor on platelets was demonstrated. The modulation of surface expression of P-selectin was assessed by flow cytometry. P-selectin expression was significantly enhanced by in vitro stimulation with recombinant rat fractalkine compared with baseline levels. Selectively inhibiting the function of recombinant fractalkine by an antagonizing antibody or the disruption of the G-protein-coupled intracellular signaling cascade of the fractalkine receptor by pertussis toxin (PTX) completely prevented fractalkine-mediated platelet activation. Preincubation with apyrase significantly attenuated the fractalkine-induced degranulation. In a flow chamber model of platelet adhesion, stimulation with fractalkine significantly enhanced platelet adhesion to collagen and fibrinogen. Similar to P-selectin expression, enhanced adhesion could be prevented by the antagonizing antibody or preincubation of platelets with PTX. Fractalkine, which is overexpressed in atherosclerosis and vascular injury, contributes to platelet activation and adhesion and hence is likely to play a pathophysiologically important role for increased thrombogenesis in vascular diseases.

Increased mature and immature CCR3 messenger RNA+ eosinophils in bone marrow from patients with atopic asthma compared with atopic and nonatopic control subjects.

BACKGROUND: Eosinophil infiltration of the bronchial mucosa is characteristic of asthma. Eosinophils differentiate from CD34(+) progenitors. Animal models suggest cooperation between IL-5 and eotaxin to allow rapid mobilization of a pool of bone marrow eosinophils followed by recruitment to the airway mucosa. OBJECTIVE: The purpose of this study was to enumerate CD34(+) cell numbers in blood and bone marrow from atopic asthmatics and control subjects and to test the hypothesis that there is an increased bone marrow pool of CCR3(+) eosinophils in patients with atopic asthma, as compared with control subjects. METHODS: Bone marrow aspirates and peripheral blood were obtained from volunteers with asthma and control volunteers. CD34(+) cell numbers were evaluated by flow cytometry, and eosinophil colony-forming activity was evaluated by methylcellulose cultures. Mature eosinophils, eosinophil myelocytes, metamyelocytes, and band forms (immature eosinophils) were enumerated by morphologic findings and immunocytochemistry for eosinophil cationic protein. CCR3 and eotaxin mRNA expression was examined by in situ hybridization, and protein expression was examined by immunocytochemistry. CCR3(+) cells were further identified with Chromotrope 2R staining. RESULTS: CD34(+) cell numbers in bone marrow were increased in atopic subjects. Numbers of eosinophil colony-forming units in blood and bone marrow did not differ between groups. Percentages of both mature and immature eosinophils were increased in bone marrow from patients with atopic asthma, but not atopic patients with no asthma or normal control subjects. CCR3 was expressed by immature and mature bone marrow eosinophils. Eotaxin was expressed by bone marrow cells from all 3 groups, but there was no increase in subjects with asthma. CONCLUSION: These findings suggest that in humans there is an increased bone marrow pool of CCR3(+) mature and immature eosinophils available for rapid mobilization in subjects with asthma but not in atopic subjects with no asthma.