Relative Increase In Lymphocytes Research Articles

Immune regulatory effects of high dose vitamin D3 supplementation in a randomized controlled trial in relapsing remitting multiple sclerosis patients receiving IFNβ; the SOLARIUM study

Multiple sclerosis (MS) is characterized by a disturbed immune homeostasis and low serum vitamin D levels are associated with an increased disease activity. While vitamin D has been hypothesized to promote the maintenance of immune homeostasis, vitamin D supplementation could be of benefit to patients with MS. The SOLAR study investigated the effects of high dose vitamin D3 supplementation on clinical outcomes in a randomized controlled trial. Here we present the immune regulatory effects, investigated in the SOLARIUM sub-study.Thirty Dutch relapsing remitting (RR) MS patients treated with IFNβ-1a received high dose vitamin D3 supplementation and 23 patients received placebo during a period of 48weeks. Lymphocytes were phenotypically characterized by flow cytometry and in vitro cytokine secretion was assessed in the presence or absence of 1,25(OH)2D3 using Luminex technology. Changes in immune regulatory parameters were determined within subjects as well as between treatment groups.The proportion of cells in the immune regulatory cell compartment (nTreg, iTreg and Breg) was not altered upon high dose vitamin D3 supplementation. Proportions of T helper subsets were not affected by vitamin D3, except for the proportion of IL4+ Th cells, which decreased in the placebo but not in the vitamin D3 group. T cell cytokine secretion increased, most pronounced for IL5 and latency activated protein of TGFβ, in the placebo group but not in the vitamin D3 group. Lymphocytes remained equally reactive to in vitro 1,25(OH)2D3.In conclusion, high dose vitamin D3 supplementation did not result in a relative increase in lymphocytes with a regulatory phenotype. However, this study supports the hypothesis that vitamin D contributes to the maintenance of immune homeostasis by preventing further disturbance of the T cell compartment early in the disease course of MS.

Relative increase in lymphocytes from as early as 1 month predicts improved response to dasatinib in chronic-phase chronic myelogenous leukemia

Lymphocytosis in response to dasatinib for chronic myelogenous leukemia (CML) may be associated with favorable response. However, it occurs at varying times and in a limited subset of patients. To identify early clinical markers for favorable responses applicable to all patients with or without lymphocytosis, we prospectively analyzed lymphocyte profiles of 50 Japanese CML patients treated with dasatinib after intolerance/resistance to imatinib. Although absolute lymphocyte counts did not differ significantly until 3 months between patients with complete molecular response (CMR) at 12 months and those without it, relative increases in lymphocyte compared with baselines differed significantly from 1 month. Patients with relative lymphocyte counts >150 % at 1 month or >200 % at 3 months had higher CMR rates at 12 months than others (57.9 vs. 23.3 %, P = 0.015, and 76.5 vs. 16.1 %, P < 0.0001, respectively). A relative increase in lymphocyte subset of CD57(+)CD14(-), CD8(+)T, or NK cells >200 % at 1 month was also significantly associated with a higher CMR rate. There were significant negative correlations between relative lymphocyte increases and BCR/ABL transcript levels. CD57(+)CD14(-) cells were a highly specific focus of proliferation. Relative increases in lymphocyte count and its subsets from 1 month are reliable early markers of favorable responses to dasatinib.

Relative Increase of Lymphocytes As Early As 1 Month After Initiation of Dasatinib Is a Reliable Predictor for Achieving Complete Molecular Response At 12 Months in Chronic Phase CML Patients Treated with Dasatinib

AbstractAbstract ▪691▪This icon denotes a clinically relevant abstract Background:Tyrosine kinase inhibitor (TKI) therapy has become the standard treatment for patients with chronic phase chronic myelogenous leukemia (CML-CP). Compared with imatinib, dasatinib is known to induce a faster and better response as a first- and second-line treatment. A unique effect of dasatinib treatment is the induction of clonal lymphocytosis with large granular lymphocyte (LGL) morphology, presumed to be the effect of off-target kinase inhibition. These LGLs are known to possess either cytotoxic T-cell (CTL) or natural-killer (NK) cell phenotype. Several reports have shown that this clonal LGL expansion is associated with a better response to dasatinib treatment.Purpose: To prospectively analyze the immunoprofile of Japanese patients treated with dasatinib, and to correlate the increase of lymphocytes and their subsets (LGL, CTL and NK cells) with the clinical efficacy of dasatinib. Method and Patients:Japanese patients with CML-CP who were resistant or intolerant to first-line imatinib therapy participated in the prospective phase II study assessing the efficacy and safety of dasatinib. Peripheral blood LGL, CTL and NK cell counts before and 2 weeks, 1 month (M), 3M, and 6M after the initiation of treatment were analyzed at the central laboratory (BML Inc.) by flow cytometry. LGL, CTL and NK cells were defined as CD57+/CD14-, CD8+/CD4- and CD56+/CD3- cells, respectively. Lymphocytosis was defined as a lymphocyte count of >3.0×109/L. The clinical efficacy of dasatinib was evaluated at 12M as complete molecular response (CMR) or less than CMR by peripheral blood quantitative RT-PCR (BML Inc.). The full data set was available for 50 out of 65 patients and was included in this analysis. Results:The median age of the patients enrolled was 57 years (range: 16 – 87 years). There were 37 male and 13 female patients. Twenty patients were switched to dasatinib due to intolerance to imatinib and 30 due to resistance. Lymphocytosis was observed in 19 patients (38%) at 3M. Of those 19 patients, 14 (73.7%) had lymphocytosis persisting at 6M. In total, 21 patients (42%) achieved CMR at 12M.The absolute count of lymphocytes, LGL, CTL or NK cells, did not differ significantly between patients who achieved CMR at 12M and those who did not (p>0.05). However, there were significant differences between these two groups in the relative increase of these cell counts. Relative increase of lymphocytes compared to baseline as early as 2 weeks after initiation of treatment was identified by univariate analysis as a significant factor associated with CMR at 12M (p=0.0348). This increase persisted at each time point observed until 6M. As for the different subsets of lymphocytes, the relative increase of CTL at 3 and 6M and LGL at 1, 3 and 6M were also significantly associated with a higher rate of CMR at 12M. When adjusted for possible confounding factors (age, sex, performance status, whether 1st or 2nd CP, resistance or intolerance to imatinib), the relative increase of lymphocytes at 1, 3 and 6M, CTL and LGL at 3 and 6M remained significant (Fig a-c).Patients who showed an increase of lymphocytes of over 1.5-fold at 1M showed a significantly higher rate of CMR at 12M (66.7% vs 25.8%, p=0.0007). Similar differences were seen in patients with increases of over 2-fold in CTL, LGL and NK cells (70.6% vs 22.6%, p=0.0011; 74% vs 21%, p=0.0003; and 57.9% vs 28.6%, p=0.0444). Detailed analysis at 3M showed a further significant difference in the treatment effect. An increase of over 2-fold in lymphocytes (81.3% vs 21.2%, p<0.0001), and of over 5-fold in CTL (85.7% vs 30%, p<0.0001), LGL (66.7% vs 30.3%, p=0.0001) and NK cells (75% vs 31.6%, p<0.0001) compared to baseline was associated with a significantly increased probability of CMR at 12M. Conclusion:Lymphocytosis after the initiation of dasatinib was seen in a substantial proportion of Japanese patients treated with dasatinib. A relative increase of lymphocytes together with LGL, CTL and NK cells, uniformly defined by flow cytometry, at 1 and 3M after the initiation of treatment were associated with a higher rate of CMR at 12M. To our knowledge, this is the first large prospective study analyzing the clinical significance of lymphocytosis associated with dasatinib therapy in Japanese patients with CML-CP using flow cytometry. Our results suggest that a relative increase of lymphocytes as early as 1M after the initiation of dasatinib is a reliable predictive marker for achieving CMR at 12M. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Hematological findings in the Norrbottnian type of Gaucher disease.

A controlled study of hematological changes was performed on 14 patients with the Norrbottnian type of Gaucher disease, seven of whom had been splenectomized at least one year before the study. Each patient had two controls matched to age, sex and habitation. Before splenectomy the patients had slight to moderate microcytic, hypochromic anemia which changed after splenectomy to macrocytic, hypochromic anemia. The splenectomized patients had a high percentage of target cells (mean frequency 33%) and a significantly increased hypo-osmotic resistance of the erythrocytes which showed a positive correlation with the number of target cells. Before removal of the spleen the patients had slight leukopenia with a relative increase of mononuclear cells and moderate thrombocytopenia. In the splenectomized patients the thrombocyte count was normal and there was moderate leukocytosis with a persistent relative increase of lymphocytes.

Organ distribution and fate of newly formed splenic lymphocytes in the pig.

The production of lymphoid cells in the pig spleen was studied autoradiographically after selective labeling of the spleen using an extracorporeal perfusion circuit. Tritiated thymidine was added as a DNA precursor. One to 4 days after local labeling of the spleen the relative and absolute number of spleen-derived lymphocytes were determined in the following organs: mesenteric, cervical and inguinal lymph nodes, thymus, bone marrow, Peyer's patches, tonsils, three different parts of the gut, lung, liver, and blood. The labeled lymphocytes which migrated to these organs were all small lymphocytes, except for some large cells in the lamina propria. In the bone marrow, however, a considerable number of the spleen-derived immigrants were transformed into plasma cells. The total number of labeled lymphocytes decreased dramatically from Day 1 to Day 4 after labeling, indicating a high percentage of short-lived cells. Within the spleen, plasma cells had the highest labeling index of about 30% at Day 1 but this dropped to only 1.5% on Day 3. The organ distribution of the splenic emigrants changed from Day 1 to Day 4 with a relative increase in lymphocytes found in lymph nodes and a decrease in the lung and intestinal wall. The newly formed splenic lymphocytes migrated to T-and B-cell areas in lymph nodes, Peyer's patches and tonsils. In the intestinal wall labeled lymphocytes were found in the lamina propria and also as intraepithelial lymphocytes. There was no obvious redistribution between organ compartments with time after labeling of the spleen. The spleen produces large numbers of lymphocytes, which show typical organ distribution and homing to areas in lymphoid and nonlymphoid organs.

T and B lymphocytes in leukemia therapy.

In order to evaluate the effect of radio- and chemotherapy on immunity, T and B lymphocyte surface receptors were studies sequentially in the blood from 28 previously untreated leukemic children. Following the initiation of chemotherapy an increase in the percent T and B cells was noted in the peripheral blood. In association with sanctuary therapy and chemotherapy there was a decrease in the total number of circulating T and B cells and a relative increase in lymphocytes lacking markers. Based on total numbers at remission the reduction in B cells was greater than in T cells, and the most marked changes occurred during sanctuary therapy. A reduction in the mean serum immunoglobulin was associated with decreasing B cell numbers.

Experimental strangulation obstruction: Evaluation of the toxicity factor with special reference to in vivo blood changes

Lengths of rabbit distal ileum measuring 15 cm. were strangulated and obstructed by tying the two ends together with umbilical tape. Peritoneal fluid (SOF) was collected from the animals at the time of their death and its effects studied in 24 recipient animals. Hemolytic clostridia and E. coli were the commonest organisms isolated from this fluid. Raw SOF, when injected in doses of 4 ml. per kilogram of body weight, produced leukopenia with relative increase of lymphocytes, hemoconcentration, and a slight rise of serum potassium in recipient animals and was lethal for them. Similar changes were produced when antibiotics were used or when the fluid had been filtered through a Seitz filter to exclude bacteria, but in the antibiotic-protected animals the survival time was significantly increased. Heating of the sterile filtrate, however, eliminated the lethal properties of the fluid and produced polymorphonuclear leukocytosis in recipient animals. It is thus concluded that exotoxins are the major lethal factors of strangulation obstruction fluid and are responsible for the lethal outcome in experimental strangulation obstruction in rabbits.

生体染色並びに墨粒貪喰による人腹水の細胞学的研究

With ascites of 19 cases of liver cirrhosis, 4 cases of tuberculous peritonitis, 3 cases nephritis, and 2 cases of cardiac insufficiency, vital observation of ascites cells were carried out by means of property tests, vital staining and carbon particle phagocytosis by performing tissue culture of these ascites. The following are the results of the observation.1. Ascites of liver cirrhosis demonstrated the average protein content of 1.24 g./dl., the cell count of 219/mm3, and increase of signet ring cells and serous cells. Large and intermediate types of phagocytes show their peculira pseudopodial movement and their vital staining and carbon particle phagocytosis are marked. In addition, tongue-shaped pseudopodial movement is noticeable.2. Ascites of tuberculous peritonitis revelaed the average protein content of 5.53 g./dl., the cell count of 1820/mm3, and small type phagocytes and lymphocytes occupy the major portion of the whole, but large and intermediate types of phagocytes are poor both in vital stainig and carbon particle phagocytosis.3. Ascites of nephrosis showed the average protein content of 0.69 m./dl., the average cell count of 17.3/mm3, an increase in the number of small type phagocytes and relative increase of lymphocytes and in general there can be recognized more of degenerated cells. As for the large and intermediate types of phagocytes early staining and early fading of vital stain are marked but their phagocytic power is poor.4. Ascites of cardiac insufficiency shows the average protein value of 2.60 g./dl., the average cell count of 150/mm3, relative increase of neutrophils. Degenerated cells are numerous and the stainability to vital stain and phagocytic power of large and intermediate phagocytes are about the same as in the case of the ascites of nephrosis.5. By means of vital observations it is possible to grasp cytological characteristics of ascites of various non-tumorous patients and it is possible to diagnose various disease by in vestigating ascites cells.

Estimation of Genetic Diversity Among Strains and Breeds of Chickens by Lymphocyte Increases Following Skin Grafting ,

INTRODUCTIONA TISSUE homograft generally elicits an immune reaction on the part of the host animal, marked by a rise in the percentage of lymphocytes in the circulating blood, whereas autografts have little or no effect, Blumenthal (1939). Craig and Hirsch (1957), using skin grafts exchanged between chickens, obtained significant negative correlation coefficients, averaging —0.64, between the relative increase in lymphocytes, measured on the fifth postoperative day, and the relationship coefficient between host and donor. Berry et al. (1958) obtained an average correlation coefficient of—0.49 (P < .05) in a similar set of experiments, using postoperative lymphocyte increases on the third day. Craig and Hirsch (1957), using two breeds, also found that grafts from one breed to the other gave a significantly greater response than grafts exchanged within the breed. These results suggested the possibility of the use of increases in lymphocytes or of postoperative lymphocyte percentages following skin …

Clinical observations on kala-azar in the fung province of the Sudan

An account is given of the investigation of 300 cases of kala-azar in the Fung Province of the Sudan. The area is inhabited by Arabs, negroids and Fellata whose habits and mode of life are fairly primitive. Diet, though sufficient in calorie value, is ill-balanced and probably deficient in Vitamins A and C. The disease is truly endemic and liable to periodic increase in endemic foci One such increase involving twenty-one cases is described. Cases probably originated mostly between August and February. There is no particular racial predisposition; individuals in a state of malnutrition and lowered resistance generally being most prone to infection. The disease affected mainly children and young adults, and was commonest in males. A history of contact or familial infection was common, especially in children. Children appeared to develop the disease more quickly than adults—the usual interval being several months after exposure to infection. The parasite was always present in the spleen; in 1 per cent. only in the peripheral blood, and in 7·5 per cent. in nasal smears. The parasite demonstrated was morphologically the same as that described in India. On postmortem examination inflammation of the bowel was usually present. Concomitant infections found were malaria, intestinal helminths, schistosomiasis, dysentery, syphilis and tuberculosis. The disease was usually a chronic infection characterized by periodic or terminal acute exacerbations. The most prevalent symptoms were fever, splenic and hepatic enlargement, emaciation, epistaxis and diarrhoea. Blood examination showed anaemia and leucopenia with a relative increase in lymphocytes and large mononuclears. Diagnosis was always confirmed by splenic puncture. The course of the disease varied under treatment. The chief complications were septic conditions of the buccal cavity and upper respiratory passages. Pneumonia, dysentery, agranulocytosis and acute intestinal haemorrhage also occurred. Several cases of antimony poisoning occurred, especially in adults. Prognosis depended primarily on the stage of the disease at which treatment commenced. Ultimate cure was always associated with splenic shrinkage in addition to disappearance of all other symptoms. Children responded to treatment more favourably than adults. Cases peculiarly resistant to antimony therapy occurred. Routine specific treatment consisted of one course of neostibosan followed if necessary by one or two courses of antimony tartrate. Treatment was controlled by splenic puncture.