1,721,139 research outputs found
OH vitamin D down-regulates in vitro production of antierithrocyte antibodies in autoimmune haemolytic anaemia
No full textBackground: Vitamin D is a well known regulator of bone and calcium balance that has multiple immune-modulating activities. Reduced levels of 25-OH vitamin D have been found in various autoimmune diseases, such as systemic lupus systemic lupus erythematous and multiple sclerosis, and its levels and supplementation did correlate with disease clinical severity. Aims: We evaluated a) the effect of vitamin D on the in vitro production of antiRBC autoantibodies in patients with autoimmune haemolytic anaemia (AIHA); b) vitamin D levels, VDR expression and immunemodulatory cytokines. Methods: Clinical and haematological parameters, serum samples and informed consent were collected at the time of enrolment from January 2013. 25-OH vitamin D levels, VDR and IL-6, IL-10, IL-17, TNF-alfa and IFN-gamma were evaluated in 40 patients and in 40 age and sex matched healthy controls, using ELISA kits. Heparinized blood samples from 7 AIHA patients were tested for anti-RBC production in unstimulated and PWM-stimulated 48h cultures with or without vitamin D at increasing concentrations (10, 20 and 40 ng/mL). The number of immunosuppressive therapy lines (steroids, immunosuppressors, rituximab, splenectomy) were retrospectively collected. Results: Laboratory features of the patients (15 males and 25 females; mean age 58 years; 18 CAD, 18 WAIHA and 4 DAT negative AIHA) are shown in Figure 1a. Vitamin D levels were significantly reduced in patients versus controls, regardless sex, age nor season at sampling. VDR was increased in patients compared to controls; IL-6, IL-10, IL-17 and IFN-gamma serum levels were reduced. As shown in Figure 1b, vitamin D (at 10, 20, and 40 ng/mL) exerted a dose dependent inhibition on in vitro production of anti-RBC antibodies, with a delta% reduction of 6, 16 and 31 in unstimulated conditions, and 2, 1, 16 in PWM-stimulated conditions, respectively. As regards treatment at sampling, 24 patients were under low dose steroids (e.g. 0,2-0,5 mg/Kg/day prednisone); vitamin D status was comparable in treated and untreated cases. Retrospectively, 2 cases were therapy naïve, 13 cases had been treated with steroid only, 15 cases with both steroid and a second line treatment (9 rituximab and 4 cyclophosphamyde), and 10 with more than 2 lines of therapy (4 splenectomy, 10 rituximab and 6 cyclophosphamyde). Vitamin D levels were significantly lower in patients who had been treated with 2 or more lines of therapy (1,72±1 versus 2,78±2 ng/mL, p=0.04).
Summary and Conclusions: Vitamin D deficiency/insufficiency was observed in patients with AIHA, both therapy naive or previously treated, with concomitant alteration of immuno-modulatory cytokine levels. Moreover, we found increased VDR expression, possibly reflecting an up-regulation due to ligand deficiency or increased shedding because of reduced receptor recruitment. Vitamin D deficiency was more evident in relapsed/refractory patients, suggesting a more pronounced immune disregulation in these cases. In vitro studies demonstrated a dose dependent inhibitory effect of vitamin D on the production of anti-RBC auto-antibodies even at very low concentrations and suggested that vitamin D supplementation may be useful in AIHA
Mesenchymal Stem Cells in Myeloid Malignancies: A Focus on Immune Escaping and Therapeutic Implications
Full text linkThe importance of the bone marrow microenvironment forming the so-called niche in physiologic hemopoiesis is largely known, and recent evidences support the presence of stromal alterations from the molecular to the cytoarchitectural level in hematologic malignancies. Various alterations in cell adhesion, metabolism, cytokine signaling, autophagy, and methylation patterns of tumor-derived mesenchymal stem cells have been demonstrated, contributing to the genesis of a leukemic permissive niche. This niche allows both the ineffective haematopoiesis typical of myelodysplastic syndromes and the differentiation arrest, proliferation advantage, and clone selection which is the hallmark of acute myeloid leukemia. Furthermore, the immune system, both adaptive and innate, encompassing mesenchymal-derived cells, has been shown to take part to the leukemic niche. Here, we critically review the state of art about mesenchymal stem cell role in myelodysplastic syndromes and acute myeloid leukemia, focusing on immune escaping mechanisms as a target for available and future anticancer therapies
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) role in hematopoiesis and in hematologic diseases: A critical review
No full textDioxin exposure and its effect on hematopoiesis and cancer have been largely investigated in both human and non-human settings. Here we systematically reviewed literature to address the question of what we know about TCDD biology and exposure. Most effects are due to TCDD interaction with a receptor of xenobiotics called AHR, which is ubiquitously represented and also works on hematopoietic myeloid and lymphoid stem cells, inducing proliferation and stem cell release from bone marrow to peripheral circulation. Epidemiologic studies on TCDD exposure demonstrated an association with onco-hematologic diseases, particularly with non Hodgkin lymphomas and multiple myeloma, and non hematologic cancers, such as sarcomas, although these relationships are affected by multiple confounding factors
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Chronic benign neutropenia in adults: laboratory and clinical parameters of a 6-year follow-up
No full textBackground: Chronic benign neutropenia (CBN) is a rare hematological condition, characterized by an absolute neutrophil counts (ANCs) lower than 1800/μl in white and 1500/μl in black people for more than 3 months. This condition can be congenital or acquired, idiopathic or secondary and may be characterized by the presence of anti-neutrophils antibodies. While congenital and acquired forms of infancy and childhood are largely studied, with particular attention to the infective diathesis, less is known about adult neutropenia. Aims: To evaluate clinical and laboratory features of chronic benign neutropenia in adult patients, focusing on ANCs variations, on the positivity for anti-neutrophil auto-antibodies and on the incidence of infectious episodes. Methods: Complete blood counts and physical examination were performed every 3-4 months in the first 2 years, then at least once a year. Anti-neutrophil antibodies were determined by direct and indirect granulocyte immunofluorescence test (GIFT method). Infectious episodes were defined according to Common Terminology Criteria for Adverse Events (Version 4.0 http://evs.nci. nih.gov). Results: 47 patients (17 males and 30 females, median age 55 years, range 25- 86 years) were followed up for a median time of 47 months (range 6-240 months). As Figure 1 shows, mean ANCs at enrolment and over time displayed a great variability, both inter and intra-subject (>500/μl in 74% and >1000/μl in 25% of patients). Considering the severity of neutropenia, we observed 23 patients (49%) with neutrophils lower than 1000/μl in at least one observation (median number of 470/μl neutrophils, range 100-969/μl). Finally, the mean ANCs observed during the follow up was significantly lower in males than in females (610/μl, range 100-1380/μl versus 1070/μl, range 100-1750/μl, respectively; P=0,02). Anti-neutrophil antibodies were detected in 18/45 patients (40%), and mean ANCs were significantly lower in positive versus negative cases (P=0,021 for 6 and 12 months time). Bone marrow evaluation showed features of dismyelopoiesis in 14 cases (56%), hypocellularity in 3 (12%) and normal morphology in 8 (32%). Flow cytometry demonstrated increased Natural Killer cells in 13 patients (28%), Cytogenetic was normal 22 cases (88%), while in 3 male patients karyotype was 45, X0 (7,6 and 3 metaphases respectively). Finally, monocyte counts were higher than 600/μl in 8 patients (17%), and 5 of them (62%) showed an NK marrow infiltrate (P=0,015). Mild splenomegaly was present in 10 patients (21%) with a mean maximal diameter of11,4 cm by ultrasonography. These cases displayed lower ANCs compared with cases without splenomegaly (835/μl, 140-1400, versus 1380/μl, 200-3239, at 3 months; P=0,03). During the study 11 patients (23%) had an infection needing oral antibiotic or antiviral therapy (7 upper respiratory tract infections, 3 Herpes Zoster Virus infections and 1 urinary tract infection); no relationship was found between the occurrence of infections and the patient’s mean ANCs value, the nadir of ANCs, and the presence of anti-neutrophil antibodies Summary and Conclusions: In spite of the alarm that produces in the general practitioner, CBN in adults is a benign disease, often incidentally diagnosed, with an infectious rate comparable to that of general population and frequent spontaneous ANCs variations. Bone marrow evaluation shows abnormal findings in a half of patients, without reaching the criteria for clonal hematological diseases, but suggesting that this condition deserves clinical follow up
Multifactorial neutropenia in a patient with acute promyelocytic leukemia and associated large granular lymphocyte expansion: A case report
Full text linkNeutropenia in the setting of acute hematological malignancies may impact disease prognosis, thus affecting therapy dose intensity. This is often due to chemotherapy‐induced aplasia as well as to the disease itself. However, chronic neutropenia deserves further investigation, as the management of reversible concomitant causes may avoid treatment delay. The present study describes a case of an acute promyelocytic leukemia patient with chronic severe neutropenia of multifactorial origin, including acute leukemia itself, chemotherapy, autoimmune activation with anti‐platelets and anti‐neutrophil antibodies positivity, and the rare association of large granular lymphocyte (LGL) expansion. As neutropenia may challenge the diagnosis and treatment of acute malignancies, clinicians and hematopathologists must discuss the differential diagnosis in order to avoid misdiagnosing and undertreating concomitant diseases. In particular, LGL chronic expansion and autoimmunity should be considered
Prognostic and predictive impact of small PNH clones in a large cohort of patients with myelodysplastic syndrome and aplastic anemia: a single-center experience
No full textThe use of high sensitive FLAER improved the detection of very small PNH clones (<1%) in aplastic anemia (AA)/myelodysplastic syndromes (MDS). Here we aimed to evaluate the prevalence of PNH clones >0.01% in AA/MDS patients tested at a single tertiary center,and to assess their impact on disease prognosis, occurrence of thrombosis, and response to current therapies. We retrospectively collected clinical and laboratory features of 869 MDS and 531 AA patients tested from March 1998 till October 2017. Table 1 shows characteristics of MDS and AA patients, divided according to PNH positivity, which was less frequent in MDS versus AA (20.3% vs 61%). Focusing on MDS, PNH+ cases were significantly more hypoplastic,and showed deeper cytopenias and higher LDH levels. Considering clone size (negative, 0.01-1%, 1.01-10%,10.01-50%, and >50% on granulocytes), we observed a significant worsening of cytopenia and raise of LDH along with clone size increase. As regards therapy, PNH+MDS showed significantly higher response rates to immunosuppressive therapies (ATG and CyA, 84% vs 44.7%, p=0.01) and to HSCT (71% vs 56.6%, p=0.09) compared to PNH-, and the cumulative probability of response to any treatment significantly improved along with clone size increase (from 52 to 100%, p=0.03). PNH+MDS
showed lower rate of evolution, and longer OS [mean 11.9+0.7 years (10.5-13.3) vs 7.3+0.3 (6.6-7.9), p<0.0001], confirmed in multivariable analysis. However, PNH+MDS had a higher incidence of thrombotic events (from 5% in PNH- to 50% in PNH+ with clone size >50%, p<0.0001). Similarly to MDS, PNH+AA showed deeper thrombocytopenia and higher LDH, and showed higher response rates to any therapy (97 vs 77% for HSCT, p=0.01; 78 vs 50% for IST, p<0.0001; and88% vs 65% considering any treatment, p<0.0001). They also showed lower rate of MDS progression and death (p=0.01 and p<0.0001), and longer OS [mean 15.8+0.43 years (14.9-16.7) vs 6.5+0.35 (5.8-7.21), p<0.0001], confirmed in multivariable analysis. Prevalence of PNH clones of any size is high in patients with MDS and AA. We firstly
show a positive impact of PNH clone positivity on response to IST and HSCT in a large MDS series and confirmed this data in AA. The presence of a PNH clone also correlated with lower disease progression and better OS. Clone size analysis suggests that even small clones (0.01- 1%) have a clinical and prognostic significance
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