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Background: Despite advances in health care for sickle cell disease patients, as well as in the improvement in reproductive issues mainly in women with the disease, pregnancy is still a challenge, both for the mother and the child, with high rates of maternal and fetal morbidity and mortality. Besides their chronic hemolytic status and vaso-occlusive events that confer systemic complications, pregnant women also have higher rates of pain episodes, infections, abortion, intrauterine growth retardation, pre-term births, eclampsia, stillbirth and the hemolysis, elevated liver enzymes and low platelets syndrome. The physiologic mechanisms of the disease in pregnancy are still unknown and chronic inflammatory responses may interfere in the adverse outcomes. The cytokine and chemokine profiles in pregnancy with sickle cell disease remain unknown. The aim of this study was to evaluate the cytokine profile of the inflammatory response of pregnant women with sickle cell disease. Method: Blood samples from 20 pregnant women with sickle cell disease, 24 women with sickle cell disease in steady state, 16 healthy pregnant women and a control group with 9 women at childbearing age were assayed for interleukin-6. Main results: Pregnant women with sickle cell disease presented high serum levels of interleukin-6, compared to healthy pregnant women (p = 0.0115). Conclusion: These data suggest that the increased production of interleukin-6 may occur during pregnancy with sickle cell disease and that the role of this cytokine in the sickle cell disease pathophysiology and pregnancy complications should be further studied. Keywords: Pregnancy, Cytokines, Inflammation, Interleukin-6, Sickle cell

Introduction: There is evidence that aldosterone plays a role in the pathogenesis of vascular calcification. The aim of this study was to evaluate the effect of spironolactone, a mineralocorticoid receptor antagonist, on the progression of coronary calcification (CC) in peritoneal dialysis patients and to identify the factors involved in this progression. Methods: Thirty-three patients with a coronary calcium score (CCS) ≥ 30, detected through multi-detector computed tomography (MDCT) and expressed in Agatston units, were randomly assigned to a group receiving 25mg spironolactone per day for 12 months (spironolactone group) and a control group not receiving this drug. The primary outcome was a percentage change in CCS from baseline to end of the study (relative progression), when a further MDCT was conducted. Patients who had progression of CC were compared with those who did not progress. Results: Sixteen patients, seven in the spironolactone group and nine in the control group, concluded the study. The relative progression of the CCS was similar in both groups, 17.2% and 27.5% in the spironolactone and control groups respectively. Fifty-seven percent of the treated patients and 67% of those in the control group presented progression in the CC scores (p = 0.697). Progressor patients differed from non-progressors because they presented higher levels of calcium and low-density lipoprotein cholesterol and lower levels of albumin. Conclusion: In peritoneal dialysis patients, spironolactone did not attenuate the progression of CC. However, large-scale studies are needed to confirm this observation. Disorders of mineral metabolism and dyslipidemia are involved in the progression of CC. RESUMO Introdução: Existem evidências de que a aldosterona exerça um papel na patogênese da calcificação vascular. O objetivo deste estudo foi avaliar o efeito da espironolactona, um antagonista do receptor mineralocorticoide, na progressão da calcificação coronariana (CC) de pacientes em diálise peritoneal, e identificar os fatores envolvidos nessa progressão. Métodos: Trinta e três pacientes com escore de cálcio coronariano (ECC) ≥ 30, detectado por tomografia computadorizada com múltiplos detectores (TCMD) e expresso em unidades de Agatston, foram randomizados para um grupo que recebeu 25 mg de espironolactona por dia durante 12 meses (grupo espironolactona) e um grupo controle que não recebeu este medicamento. O desfecho primário foi a mudança percentual do ECC do início para o final do estudo (progressão relativa), quando uma nova TCMD foi realizada. Os pacientes que tiveram progressão de CC foram comparados com aqueles que não progrediram. Resultados: Dezesseis pacientes, sete no grupo espironolactona e nove no grupo controle, concluíram o estudo. A progressão relativa do ECC foi semelhante nos dois grupos, 17,2% e 27,5% nos grupos espironolactona e controle, respectivamente. Cinquenta e sete por cento dos pacientes tratados e 67% daqueles no grupo controle apresentaram progressão nos escores de CC (p = 0,697). Os pacientes progressores diferiram dos não progressores porque apresentaram níveis séricos mais elevados de cálcio e LDL-colesterol e menores níveis de albumina. Conclusão: Em pacientes em diálise peritoneal, a espironolactona não atenuou a progressão da CC. No entanto, estudos em grande escala são necessários para confirmar essa observação. Distúrbios do metabolismo mineral e dislipidemia estão envolvidos na progressão da CC.

Regular physical activity prevents and treats cancer patients by assisting and improving the immune system. Co-stimulatory molecules that activate the immune system have been studied in cancer, such as immune checkpoint molecules of the CD40/CD40L pathway. This study aimed to characterize plasma levels of soluble CD40 (sCD40) and CD40 ligand (sCD40L) in older people with gastrointestinal tract (GIT) cancer and associate results with physical activity. This prospective and exploratory cohort study was performed with 24 older people with GIT cancer and 23 healthy elderly individuals as controls. Physical activity level was classified as active or sedentary according to the International Physical Activity Questionnaire-Short Form (IPAQ-SF). Plasma levels of sCD40 and sCD40L were determined using Enzyme-Linked Immunosorbent Assay. Plasma levels of sCD40 were higher, while sCD40L were lower (p = 0.0171) in older people with GIT cancer than controls (p = 0.0038). Regarding physical activity, active older people with GIT cancer presented lower plasma levels of sCD40 and sCD40L than those sedentary with GIT cancer (p = 0.0228 and p = 0.0236), respectively. Our findings suggest that GIT cancer stimulates the immune system in older people, elevates levels of sCD40, and reduces levels of sCD40L. Physical activity may be a protective factor for the immune system of these patients since it acts on sCD40/sCD40L pathway.

Among the lysosomal storage disorders, Gaucher disease (GD) features some of the most striking alterations in the immune system, including increased levels of cytokines and chemokines. Although studies have demonstrated the efficacy of enzyme replacement therapy (ERT) for GD, the ideal dosage remains controversial. In this study, we report differences in levels of cytokines (IL-6, TNF-a, and IFN-y) and chemokines (IL-8, IP-10, and MCP-1) in patients with GD type 1 treated with different ERT dosages and treatment durations. Patients were recruited from two ERT centers in Brazil and divided into two groups according to treatment facility. Comparison between groups showed that patients in group 1 had received ERT for longer (p=0.0078) and at higher doses (p=0.0002) than those in group 2. Patients in group 1 exhibited decreased levels of IL-6 (p=0.0006), TNF-α (p

BACKGROUND AND OBJECTIVES The prognosis of colorectal cancer (CRC) has improved in the last decades, however, a lower overall survival persists in the elderly. The understanding of immunity changes in the elderly with CRC will allow the emergence of new treatments with higher response rates. 4-1BB and CD40L, an immune checkpoint stimulator, play an important role in T-cell responses and platelets. Our aim was to characterize the soluble levels of CD40L and 4-1BB in CRC elderly patients. METHODS A cross-sectional study was performed in 41 patients with CRC and 35 healthy elderly controls. Patients with CRC were divided into three groups according to staging: 13 patients with advanced tumor restricted to the organ (stages II); 16 patients with lymph node metastasis (stage III); and 12 patients with distant metastasis (stage IV). RESULTS There were higher levels of soluble s4-1BB and sCD40L in CRC elderly stage II patients when compared with healthy controls (P = .0009 and P

22q11.2 deletion syndrome (22q11.2DS) has a heterogeneous presentation that includes multiple congenital anomalies and immunodeficiency, one of the most striking features. Usually, it is characterized by T cell lymphopenia, B cell dysfunction and autoimmunity. Here, we describe an unusual case of 22q11.2DS in a patient with lymphoproliferative disorder, polyautoimmunity and hypogammaglobulinemia.

Pregnancy in sickle cell disease is a problem due to the adverse outcomes related to the disease. Research into the role of chemokines in sickle cell disease is available, but studies investigating the disease in pregnancy are scarce. Our data show the chemokine profiles of pregnant women with sickle cell disease compared with control groups. There were no differences in MCP-1 level among the groups, but IL-8 and MIG were likely related with disease activity. In addition, levels of IP-10 were higher in pregnant women with sickle cell disease and, interestingly, RANTES levels were higher in normal pregnancy when compared to pregnancy in sickle cell disease. More studies should be encouraged to fully elucidate chemokine activity during pregnancy in sickle cell disease.

Gaucher Disease (GD) is a rare autosomal recessive disorder caused by the deficient activity of beta-glucocerebrosidase. GD is one of the lysosomal storage diseases with the most remarkable alterations in the immune system, and that may manifest clinically as autoimmune disorders and malignancy. We reported the immunological evaluation of a patient with GD and lupus nephritis. Decreased absolute values of T, and NK, and an inversion of CD4(+)/CD8(+) ratio, low levels of IgM and normal B cells were found when compared to reference values in a Brazilian population. Absence ofCD4(+)CD25(high)Foxp3(+) Treg and high levels of total NKT, iNKT cells and CD8(+) iNKT subsets were also observed when compared to the healthy control and GD patient without lupus nephritis. Treg subset and CD8(+) iNKT abnormalities might be involved in severe lupus nephritis in a GD patient. We conclude by emphasizing the importance of the immunological evaluation on early diagnosis of autoimmunity contributing to reduce mortality and morbidity of these patients.