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Background: The serum tryptase level is used as a diagnostic marker in mastocytosis and is considered to reflect the burden of (neoplastic) mast cells (MC). Methods: In the present study, serum tryptase levels were measured in patients with mastocytosis by fluoroenzyme immunoassay and compared with the extent of infiltration of the bone marrow (BM) by neoplastic MC, determined by tryptase immunohistochemistry. Sixteen patients with cutaneous mastocytosis (CM) and 43 patients with systemic mastocytosis (SM) were examined. Results: In most patients with CM (defined by the absence of dense compact MC infiltrates in tryptase-stained BM sections), normal or near-normal serum tryptase levels (median 10 ng/ml, range 2–23 ng/ml) were measured. By contrast, in the vast majority of patients with SM, elevated serum tryptase levels (median 67 ng/ml) were found. In addition, there was a significant correlation between the grade of infiltration of the BM by neoplastic MC and tryptase levels in patients with SM (r = 0.8). Moreover, enzyme levels differed significantly among the groups of patients with different types of SM. The highest levels (>900 ng/ml) were detected in the patient with MC leukemia, 2 patients with slowly progressing SM and high MC burden (smoldering SM) and 1 patient with indolent SM. In contrast, in all 3 patients with isolated BM mastocytosis (no skin lesions and no signs of multiorgan involvement), serum tryptase levels were <20 ng/ml. Conclusions: In summary, our data suggest that the measurement of serum tryptase is a reliable noninvasive diagnostic approach to estimate the burden of MC in patients with mastocytosis and to distinguish between categories of disease.

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T cell antigen receptors (TCRs) and B cell antigen receptors (BCRs) transmit low-grade signals necessary for the survival and maintenance of mature cell pools. We show here that TC21, a small GTPase encoded by Rras2, interacted constitutively with both kinds of receptors. Expression of a dominant negative TC21 mutant in T cells produced a rapid decrease in cell viability, and Rras2(-/-) mice were lymphopenic, possibly as a result of diminished homeostatic proliferation and impaired T cell and B cell survival. In contrast, TC21 was overexpressed in several human lymphoid malignancies. Finally, the p110delta catalytic subunit of phosphatidylinositol-3-OH kinase (PI(3)K) was recruited to the TCR and BCR in a TC21-dependent way. Consequently, we propose TC21 directly links antigen receptors to PI(3)K-mediated survival pathways.

The aim of the present study was to explore the diagnostic value of the immunophenotypic analysis of bone marrow mast cells (BMMC) in indolent systemic mast cell disease (SMCD) patients. For that purpose, a total of 10 SMCD patients and 19 healthy controls were analyzed. Our results show that BMMC from SMCD are different from normal BMMC with regard to both their light scatter and immunophenotypic characteristics. Accordingly, forward light scatter (FSC), side (90°) light scatter (SSC), and baseline autofluorescence levels were higher in BMMC from indolent SMCD patients than they were in control subjects. From the immunophenotypic point of view, the most striking findings were the constant expression of CD2 (P = .0001), CD25 (P = .0001), and CD35 (P = .06) molecules by BMMC from SMCD patients, markers that were absent from all normal controls. In contrast, CD71, absent in BMMC from indolent SMCD, was positive in BMMC from normal subjects. Although, slight differences between BMMC from SMCD patients and normal controls were found in several other markers, they did not reach statistical significance. In conclusion, our results show that simultaneous assessment of FSC/SSC and reactivity for the CD117, CD2, CD25, CD33, and CD35 forms the basis for the immunophenotypic characterization of BMMC from SMCD in adults and should be integrated with clinical and morphologic studies for the diagnosis of the disease.

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From 1987 to 1995, a retrospective case study was conducted at the Ramon y Cajal Hospital in Madrid, Spain, a public teaching hospital with 1,100 beds, to determine the clinicoepidemiologic characteristics, survival, and prognostic factors of patients with visceral leishmaniasis (VL) and human immunodeficiency virus (HIV) infection. The prevalence of VL in HIVϩ patients compared with HIVϪ patients was studied. Epidemiologic, clinical, and parasitologic characteristics, as well as the effects of treatment, prognosis, and survival in 54 HIVϩ patients (90 episodes) with VL were defined. Comparative survival studies among patients with and without acquired immunodeficiency syndrome (AIDS)-defining criteria and multivariate analysis of survival risk factors were performed. The prevalence of VL in patients with AIDS was much higher than in immunocompetent individuals. In spite of a good initial response to treatment for VL, 60.6% of the patients had relapsed by the end of one year. Mortality from the first episode was 18.5%, and 24% died in the first month after diagnosis of any VL episode. The mean survival of the 29 patients who died was 10.27 months. Survival in patients with and without AIDS at the time of the first episode of VL was compared at 30 months: 53.7% versus 20.5% (P ϭ 0.00149). We found no significant difference (P ϭ 0.24) in the survival of HIVϩ patients who had died of VL without AIDS at the time of the first episode of VL compared with those of a control group of 413 dead patients with AIDS without VL. A diagnosis of AIDS at the time of the first episode of VL and thrombocytopenia were the only risk factors found related to survival. We conclude that in AIDS patients, VL is a recurrent disease that is highly prevalent and whose clinical course is modified by HIV.