Serum Tryptase Levels in Patients with Mastocytosis: Correlation with Mast Cell Burden and Implication for Defining the Category of Disease

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.

[1]  R. Valenta,et al.  Expression of mast cell tryptase by myeloblasts in a group of patients with acute myeloid leukemia. , 2001, Blood.

[2]  P. Valent,et al.  Diagnosis of mastocytosis: general histopathological aspects, morphological criteria, and immunohistochemical findings. , 2001, Leukemia research.

[3]  K. Lennert,et al.  Diagnostic criteria and classification of mastocytosis: a consensus proposal. , 2001, Leukemia research.

[4]  L. Scott,et al.  Soluble stem cell factor receptor (CD117) and IL-2 receptor alpha chain (CD25) levels in the plasma of patients with mastocytosis: relationships to disease severity and bone marrow pathology. , 2000, Blood.

[5]  R. Parwaresch,et al.  Recent Advances in Mastocytosis Research , 1999, International Archives of Allergy and Immunology.

[6]  L. Schwartz,et al.  The potential clinical utility of serum α-protryptase levels , 1999 .

[7]  D. Heitjan,et al.  Activating and dominant inactivating c-KIT catalytic domain mutations in distinct clinical forms of human mastocytosis. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[8]  N. Sepp,et al.  Identification of activating c-kit mutations in adult-, but not in childhood-onset indolent mastocytosis: a possible explanation for divergent clinical behavior. , 1998, The Journal of investigative dermatology.

[9]  D. Metcalfe,et al.  Clinical correlates of the presence of the asp816Val c‐kit mutation in the peripheral blood mononuclear cells of patients with mastocytosis , 1998, Cancer.

[10]  K. Lennert,et al.  Diagnostic value of immunostaining for tryptase in patients with mastocytosis. , 1998, The American journal of surgical pathology.

[11]  A. Órfão,et al.  Indolent systemic mast cell disease in adults: immunophenotypic characterization of bone marrow mast cells and its diagnostic implications. , 1998, Blood.

[12]  A. Chott,et al.  Detection of mi transcription factor (MITF) mRNA in a case of myelodysplastic syndrome and bone marrow mastocytosis. , 1998, Wiener klinische Wochenschrift.

[13]  A. Órfão,et al.  Immunophenotypic Characterization of Human Bone Marrow Mast Cells. A Flow Cytometric Study of Normal and Pathological Bone Marrow Samples , 1998, Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology.

[14]  P. Ruck,et al.  Systemic mast cell disease (mastocytosis). General aspects and histopathological diagnosis. , 1997, Histology and histopathology.

[15]  A. Órfão,et al.  Sequential immunophenotypic analysis of mast cells in a case of systemic mast cell disease evolving to a mast cell leukemia. , 1997, Cytometry.

[16]  W. Vainchenker,et al.  A new c‐kit mutation in a case of aggressive mast cell disease , 1997, British journal of haematology.

[17]  Laura H. Tang,et al.  Somatic c-KIT activating mutation in urticaria pigmentosa and aggressive mastocytosis: establishment of clonality in a human mast cell neoplasm , 1996, Nature Genetics.

[18]  B. Zweiman,et al.  The alpha form of human tryptase is the predominant type present in blood at baseline in normal subjects and is elevated in those with systemic mastocytosis. , 1995, The Journal of clinical investigation.

[19]  Y. Suzuki,et al.  Identification of a point mutation in the catalytic domain of the protooncogene c-kit in peripheral blood mononuclear cells of patients who have mastocytosis with an associated hematologic disorder. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[20]  W. Travis,et al.  Hematologic manifestations of systemic mast cell disease: a prospective study of laboratory and morphologic features and their relation to prognosis. , 1991, The American journal of medicine.

[21]  K. Austen,et al.  Systemic mastocytosis: retrospective review of a decade's clinical experience at the Brigham and Women's Hospital. , 1991, The Journal of investigative dermatology.

[22]  D. Metcalfe.  The liver, spleen, and lymph nodes in mastocytosis. , 1991, The Journal of investigative dermatology.

[23]  D. Metcalfe,et al.  Classification and diagnosis of mastocytosis: current status. , 1991, The Journal of investigative dermatology.

[24]  E. Bergstralh,et al.  Systemic Mast Cell Disease: ANALYSIS OF 58 CASES AND LITERATURE REVIEW , 1988, Medicine.

[25]  H. S. Earl,et al.  Tryptase levels as an indicator of mast-cell activation in systemic anaphylaxis and mastocytosis. , 1987, The New England journal of medicine.

[26]  W. Travis,et al.  Mast cell leukemia: report of a case and review of the literature. , 1986, Mayo Clinic proceedings.

[27]  S. Eridani,et al.  Mast cell leukaemia: evidence for bone marrow origin of the pathological clone , 1986, British journal of haematology.

[28]  K. Lennert,et al.  Bone marrow findings in systemic mastocytosis. , 1985, Human pathology.

[29]  K. Lennert,et al.  Tissue mast cells in health and disease. , 1985, Pathology, research and practice.

[30]  S. Hsu,et al.  Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. , 1981, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[31]  K. Lennert,et al.  Mast cells and mast cell neoplasia: a review * , 1979, Histopathology.

[32]  P. Valent,et al.  Biology, classification and treatment of human mastocytosis. , 1996, Wiener klinische Wochenschrift.