Ana Paula Alegretti

Mesenchymal stem cell therapy and acute graft-versus-host disease: a review.

Mesenchymal stem cells (MSCs) are being widely studied as potential cell therapy agents due to their immunomodulatory properties, which have been established by in vitro studies and in several clinical trials. Within this context, mesenchymal stem cell therapy appears to hold substantial promise, particularly in the treatment of conditions involving autoimmune and inflammatory components. Nevertheless, many research findings are still contradictory, mostly due to difficulties in characterization of the effects of MSCs in vivo. The purpose of this review is to report the mechanisms underlying mesenchymal stem cell therapy for acute graft-versus-host disease, particularly with respect to immunomodulation, migration, and homing, as well as report clinical applications described in the literature.

Expression of CD55 and CD59 on peripheral blood cells from systemic lupus erythematosus (SLE) patients.

CD55 and CD59 are glycosylphosphatidylinositol-anchored proteins with complement inhibitory properties. CD55 inhibits the formation of C3 convertases, and CD59 prevents the terminal polymerisation of the membrane attack complex. It has been reported that SLE patients seems to have an acquired deficiency of these proteins associated with secondary autoimmune haemolytic anaemia and lymphopenia. The aim of this study was to evaluate the presence of altered CD55 and CD59 expression on peripheral blood cells from SLE patients. Flow cytometric analyses were performed on red and white blood cells from 23 SLE patients and 23 healthy controls. We observed more CD55- and CD59-lymphocytes (p=0.005 and p=0.019, respectively), and CD59-granulocytes (p=0.045) in SLE patients than in controls. These results suggest there is an altered pattern of CD55 and CD59 expression on the peripheral blood cells of SLE patients, and it may play a role in the cytopenias in these patients.

Diminished expression of complement regulatory proteins on peripheral blood cells from systemic lupus erythematosus patients.

CD55, CD59, CD46, and CD35 are proteins with complement regulatory (Creg) properties that ensure cell and tissue integrity when this system is activated. The aim of this study was to evaluate the Creg expression on peripheral blood cells from SLE patients and its association with cytopenia and disease activity. Flow cytometric analyses were performed on blood cells from 100 SLE patients and 61 healthy controls. Compared with healthy controls, we observed in SLE patients with lymphopenia and neutropenia decreased expression of CD55, CD59, and CD46 (P < 0.05). In SLE patients with anemia, CD59 and CD35 were decreased on red blood cells. Furthermore, there was a negative correlation between CD55 and CD59 on neutrophils and the disease activity. The results suggest there is an altered pattern of Creg expression on the peripheral blood cells of SLE patients, and the expression is correlated with disease activity and/or with activation of the complement system.

Expressão de proteínas reguladoras do complemento CD55, CD59, CD35 e CD46 na artrite reumatoide

Rheumatoid arthritis (RA) is an autoimmune disease associated with polyarticular inflammatory synovitis affecting mainly peripheral joints. It affects approximately 1% of the world population, being two to three times more prevalent in women. Rheumatoid arthritis has a complex and multifactorial pathogenesis. The synovium of the affected joints is infiltrated by T and B lymphocytes, macrophages, and granulocytes. The rheumatoid synovium has proliferative characteristics, forming the pannus, which invades cartilage and bone, leading to normal architecture destruction and function loss. The decreased expression of complement regulatory proteins (CRP) seems to play an important role in RA activity, and is associated with worsening of the clinical symptoms. In several models of autoimmune diseases, the overactivation of the complement system (CS) is the cause of disease exacerbation. This article aimed at reviewing the main aspects related to CS regulation in RA in order to provide a better understanding of the potential role of this system in the pathophysiology and activity of the disease.

Vitamin D levels and cytokine profiles in patients with systemic lupus erythematosus

Objectives To evaluate the expression of Th1, Th2, and Th17 cytokines in patients with systemic lupus erythematosus (SLE), and verify the association between serum cytokine levels and vitamin D concentration. Methods The sample consisted of 172 patients with SLE. 25-Hydroxyvitamin D (25(OH)D) levels were measured by chemiluminescence and 25(OH)D levels <20 ng/mL were considered to reflect vitamin D deficiency. Serum cytokine levels were measured in once-thawed samples, using a Th1/Th2/Th17 CBA (cytometric beads array) kit. Results One hundred and sixty-one (93.6%) patients were women and 128 (74.4%) were of European descent. Mean patient age was 40.5 ± 13.8 years, and mean age at diagnosis was 31.5 ± 13.4 years. At the time of study entry, patients had a median (IQR) SLEDAI of 2 (1–4) and SLICC of 0 (0–1). Mean 25(OH)D concentration was 25.4 ± 11.04 ng/mL. Fifty-nine (34.3%) patients had a vitamin D deficiency. No statistically significant associations were identified between cytokine and vitamin D levels. The most significant finding was a positive correlation between INF-α levels and SLEDAI (rs = 0.22, p = 0.04). Conclusion Although vitamin D deficiencies are highly prevalent in patients with SLE, vitamin D levels were not significantly associated with patient cytokine profiles. The positive correlation between IFN-α levels and SLEDAI showed in this study corroborates other findings in the literature. The present results did not replicate those of in vitro studies of the effect of vitamin D levels on cytokine profiles. Placebo-controlled intervention trials of the effect of vitamin D on cytokine profiles are still required before any definitive conclusions can be drawn regarding the association between these variables.

The role of complement regulatory proteins in peripheral blood cells of patients with systemic lupus erythematosus: Review

CD55, CD59, CD35 and CD46 are cell membrane proteins that have regulatory properties on the activation of the complement cascade. Deficiency in the expression of these proteins may be associated with lower protection of healthy cells against complement mediated lysis and also with the accumulation of immune complexes in tissues. Few studies assess the expression of these proteins in patients with SLE and the mechanisms that regulate reduction in cellular expression, whereas its impact on manifestations of systemic lupus erythematosus is still unknown.

The expression of CD56 antigen is associated with poor prognosis in patients with acute myeloid leukemia

Background The expression of CD56 is considered a bad prognostic factor for overall survival, lower rates or short complete remission and extramedullary invasion but the results are controversial. The importance of validating new prognostic parameters in acute leukemias was the reason to investigate the CD56 expression in blast cells of patients with acute myeloid leukemia. Methods A cohort of 48 patients treated at Hospital de Clinicas de Porto Alegre and diagnosed with acute myeloid leukemia as classified by the French-American-British group (FAB) criteria using cell morphology, cytochemistry and flow cytometry were evaluated. Results Eight cases (16.7%) were CD56 positive without correlation to age or gender. The highest incidence of CD56 positivity was in FAB subtypes M4 and M5. The death rate during induction was not significantly different between patients with and without CD56 expression (62.5% vs. 27.5%; p-value = 0.097). However, patients that expressed CD56 had significantly lower overall survival than those who did not (mean 4.0 months vs. 14.5 months; p-value = 0.03). Conclusions The data suggest that expression of CD56 in acute myeloid leukemia may be indicative of poor prognosis because it is associated with a shorter overall survival. The death rate during induction was not significantly different despite an apparent difference in proportions between groups.

O papel das proteínas reguladoras do complemento CD55/CD59 em células de sangue periférico de pacientes com lúpus eritematoso sistêmico

CD55 and CD59 are glycosylphosphatidylinositol-anchored proteins with regulatory properties on the activating cascades of the complement system. This regulation occurs through inhibition of the C3-convertase formation by CD55, and prevention of the terminal polymerization of the membrane attack complex by CD59. Deficiency in the expression of these proteins can be associated with increased susceptibility to complement-mediated cell death. Systemic lupus erythematosus patients with hemolytic anemia and lymphopenia seem to have an acquired deficiency of CD55 and CD59 proteins. However, the mechanisms involved in this deficiency and its impact on the clinical manifestation of SLE needs to be further investigated.

Exercise on Progenitor Cells in Healthy Subjects and Patients with Type 1 Diabetes.

PURPOSE To evaluate the acute effect of aerobic exercise (AE) and resistance exercise (RE) on the release of endothelial progenitor cell (EPCs, CD34+/KDR+/CD45 dim) and vascular function in type 1 diabetes (T1DM). METHODS Fourteen men with T1DM and 5 nondiabetic controls were randomly assigned to 40-min AE (60% VO 2peak) and RE sessions (60% 1-RM). The study had a crossover design, and interventions were 1 wk apart. Venous occlusion plethysmography (blood flow, reactive hyperemia, and vascular resistance) and blood collection (EPC levels, flow cytometry) were done immediately before and after exercise sessions. RESULTS Patients were 30.3 ± 1.6 yr-old, HbA1c 7.7% ± 0.2%; controls were 26.8 ± 2.3 yr-old. Groups did not differ in EPC levels at baseline or in relation to exercise. Over time, exercise did not induce changes in patients with T1DM, whereas, in controls, EPCs were decreased after AE (-10.7%, P = 0.017) and increased after RE (+12.2%, P = 0.004). Compared with baseline, blood flow increased and vascular resistance decreased after RE in both groups. Reactive hyperemia was increased 10 min after AE and RE sessions in patients with T1DM (36.5% and 42.0%, respectively) and in controls (35.4% and 74.3%), but no group differences were observed between groups in response to exercise. CONCLUSIONS Despite the increased vascular reactivity in both groups after both exercise sessions, EPCs were only influenced by exercise in controls. The unchanged number of EPCs in T1DM after exercise sessions might indicate a blunted endothelium regenerating capacity, revealing an early deterioration of the functional arterial characteristics not disclosed by only evaluating vascular functional variables.

Assessment of Mean Platelet Volume in Patients with Systemic Lupus Erythematosus

Introduction: The Mean Platelet Volume (MPV) is a platelet activation biomarker that has been recently correlated with disease activity in SLE. We aimed to evaluate the MPV in patients with SLE comparing it with healthy individuals, to study the correlation between MPV and SLE Disease Activity Index (SLEDAI) in SLE patients and to analyze possible correlation between MPV and Erythrocyte Sedimentation Rate (ESR), C-Reactive Protein (CRP), and complement components C3 and C4. Methods: This is a cross-sectional study in which 81 patients with SLE according to the American College of Rheumatology (ACR) diagnostic classification criteria and 58 healthy controls were included. Active disease was defined as SLEDAI>0. Results: Patients with active SLE had decreased MPV when compared to inactive disease group (10.0±0.7fL vs. 10.7±1.0fL, p=0.005, respectively) and when compared to control group (10.9±1.0fL, p<0.001). Our study found a weak negative correlation between the SLEDAI and the MPV (r=-0.29, p=0.009). There was no correlation between MPV and CRP, ESR, C3 and C4. Also, no correlation between SLEDAI and CRP, ESR, C3 and C4 was found. Conclusion: MPV decreases in patients with active SLE and is inversely correlated with SLEDAI.