acid-phosphatase and Hypergammaglobulinemia

Topics: Acid Phosphatase; Antigens; Blood Protein Disorders; Gaucher Disease; Glucosylceramidase; Glucosylceramides; Humans; Hypergammaglobulinemia; Multiple Myeloma

Lymphocyte activation is crucial for the generation of immune responses. In vitro studies have demonstrated that TRAPs are critical regulators of lymphocyte activation. However, more recent in vivo studies have demonstrated that with the exception of LAT, TRAPs, such as SIT, NTAL, and LAX, only minimally affect immune cell functions. Additional studies have suggested that the mild or the apparent lack of a phenotype displayed by most TRAP KO mice may be explained by functional redundancy among this family of adaptors. In fact, it has been shown that the phenotype of NTAL/LAT or SIT/TRIM double-deficient mice is more severe than that of the single KOs. Here, we have evaluated whether SIT and the related transmembrane adaptor LAX have overlapping functions by generating SIT/LAX DKO mice. We show that DKO, in contrast to single KO mice, accumulate large numbers of activated CD4(+) T cells in the spleen. Moreover, conventional B cells from DKO mice are hyperproliferative upon CD40 stimulation. Additionally, we found that DKO mice displayed an expansion of the B1 cell pool in the peritoneal cavity, hypergammaglobulinaemia, and an enhanced immune response to the T1-independent antigen, TNP-LPS. Finally, we demonstrate that SIT/LAX double deficiency resulted in a more pronounced breakdown of peripheral tolerance and the development of autoimmunity characterized by ANAs and renal disease (glomerulonephritis and proteinuria). Collectively, our data indicate that SIT and LAX are important negative regulators of immune responses that functionally cooperate.

Topics: Acid Phosphatase; Adaptor Proteins, Signal Transducing; Adaptor Proteins, Vesicular Transport; Animals; Autoimmunity; B-Lymphocyte Subsets; CD4-Positive T-Lymphocytes; CD40 Antigens; Hypergammaglobulinemia; Isoenzymes; Membrane Proteins; Mice; Mice, Knockout; Peritoneal Cavity; Tartrate-Resistant Acid Phosphatase

Morphological, immunologic, and functional properties of peripheral blood cells from two patients with chronic proliferations of granular lymphocytes are described. Cells from both patients showed a heterogeneous pattern from both a morphological and immunologic standpoint, indicating a polyclonal, rather than a monoclonal, expansion of these cells. In fact, both large and small-to-medium-sized granular lymphocytes were observed, and different percentages of positivity were found in the analysis with a large panel of monoclonal antibodies. Serologic and histologic features support the hypothesis that this lymphocytosis could be secondary to bacterial or viral infections rather than a primary event, suggesting that these patients may have chronic reactive immunoregulatory disorders.

Topics: Acid Phosphatase; Adult; Antigens, Viral; Bone Marrow Cells; Carrier State; Cytoplasmic Granules; Glucuronidase; Hepatitis B Antigens; Hepatitis, Chronic; Hepatomegaly; Herpesvirus 4, Human; Humans; Hypergammaglobulinemia; Lymphocytes; Lymphocytosis; Male; Middle Aged; Monocytes; Naphthol AS D Esterase; Salmonella Infections

Topics: Acid Phosphatase; Bone Marrow; Diagnosis, Differential; Humans; Hypergammaglobulinemia; Multiple Myeloma; Naphthol AS D Esterase; Plasma Cells; Waldenstrom Macroglobulinemia

Acid phosphatase activity was studied cytochemically in bone marrow plasma cells of 32 multiple myelomas, 45 non-myelomatous monoclonal gammopathies and 20 normal subjects. We have found significant differences among these three groups (P less than 0.001). The usefulness of this cytochemical reaction for the study of monoclonal gammopathies is discussed.

Topics: Acid Phosphatase; Aged; Bone Marrow; Clinical Enzyme Tests; Diagnosis, Differential; Hemoglobins; Humans; Hypergammaglobulinemia; Leukocyte Count; Middle Aged; Multiple Myeloma; Plasma Cells

The activity of acid phosphatase in bone marrow plasma cells was investigated by a cytochemical method in 12 patients with multiple myeloma, in 12 patients with benign monoclonal gammopathy and in 5 normal controls. The activity of acid phosphatase was significantly higher in the multiple myeloma patients compared with the activity observed in controls and in benign monoclonal gammopathy patients (p less than 0.001). It is therefore suggested that this method may be a valuable adjunct in the differential diagnosis of monoclonal immunoglobulinemias .

Topics: Acid Phosphatase; Adult; Aged; Bone Marrow Examination; Diagnosis, Differential; Female; Histocytochemistry; Humans; Hypergammaglobulinemia; Male; Middle Aged; Multiple Myeloma; Neoplasm Staging; Plasma Cells

Three plasma cell enzymatic reactions--ATPase, acid phosphatase (AP), alpha-naphthyl acetate esterase (alpha-NAE)--were tested in a large number of bone marrow samples from patients with multiple myeloma (MM), benign monoclonal gammapathy (BMG)--idiopathic (iBMG) and secondary (sBMG)--, polyclonal hypergammaglobulinemia (PH), Waldenström's macroglobulinemia (WM) and from normoglobulinemic subjects (NS). The purpose of the present study was to evaluate the significance of these reactions in differential diagnosis of BMG and initial or atypical MM. For each reaction results were expressed as scores and normal limits were statistically established. Our findings in MM, HP and NS are consistent with previous reports (similar enzymatic pattern in NS and PH; depressed ATPase activity, raised AP and alpha-NAE activities in most MM cases). In the BMG class, ATPase activity was normal in about 40% of iBMG, while it was depressed in other cases; most sBMG had diminished ATPase activity. AP patterns were normal for both BMG groups. alpha-NAE activity was normal in 50% of iBMG, while it was raised in the other cases. All the reactions were normal in WM. In a bayesian analysis of cytochemical patterns of NS and MM subjects ATPase showed the highest diagnostic significance, followed by alpha-NAE and AP. ATPase, therefore, seems to be the most useful criterion for the diagnosis of initial MM; low ATPase score BMG patients should therefore be carefully followed-up.

Topics: Acid Phosphatase; Adenosine Triphosphatases; Bone Marrow; Clinical Enzyme Tests; Diagnosis, Differential; Humans; Hypergammaglobulinemia; Multiple Myeloma; Naphthol AS D Esterase; Plasma Cells

Plasma cell acid phosphatase has been studied in 51 patients, 30 of whom were affected with multiple myeloma (MM) and 21 with nonmyelomatous monoclonal immunoglobulinemias (NMMI). Scoring of results displayed a highly significant difference between the median of the MM and NMMI group (343 vs. 204). The use of plasma cell acid phosphatase as a further criterion in the differential diagnosis of monoclonal immunoglobulinemiasis emphasized.

Topics: Acid Phosphatase; Clinical Enzyme Tests; Diagnosis, Differential; Humans; Hypergammaglobulinemia; Multiple Myeloma; Plasma Cells

The acid phosphatase activity has been studied cytochemically in bone marrow plasma cells of 12 patients with multiple myeloma and 15 with non-myeloma plasmocytosis. The acid phosphatase activity has been significantly higher in the myeloma group. The utilization and usefulness of this cytochemical reaction for the diagnosis of multiple myeloma are proposed.

Topics: Acid Phosphatase; Aged; Bone Marrow Cells; Clinical Enzyme Tests; Diagnosis, Differential; Female; Humans; Hypergammaglobulinemia; Immunoglobulin A; Male; Middle Aged; Multiple Myeloma; Plasma Cells

Peripheral blood smears and bone-marrow smears from 29 patients with malignant M-components (25 with multiple myeloma and 4 with malignant lymphoma), 13 patients with benign monoclonal gammopathy (BMG), and 20 patients with polyclonal reactive plasmacytosis were examined by leucocyte alkaline phosphatase score (LAP-score) and by acid phosphatase score in plasma cells from bone-marrow smears. Furthermore, tissue sections from marrow biopsies from all patients were examined by the three-layer unlabelled immunoperoxidase technique to detect cytoplasmic immunoglobulin. The LAP-score was significantly higher in patients with malignant M-components than in patients with BMG and also higher in IgA and IgG myeloma than in IgA and IgG BMG, but the latter difference was not significant. Furthermore, a significant positive correlation between paraprotein concentration and LAP-score was found in multiple myeloma. Acid phosphatase score in plasma cells showed no clear distinction between multiple myeloma and BMG. Immunohistochemical examination showed a distinct monoclonal pattern in both multiple myeloma and BMG, allowing identification of the M-component which in all cases corresponded to the M-component detected by serum examination. Cells producing immunoglobulin classes not matching the M-component were more rare in multiple myeloma than in BMG, but the difference between the two conditions was quantitative and allowed no clear distinction.

Topics: Acid Phosphatase; Bone Marrow; Humans; Hypergammaglobulinemia; Immunoenzyme Techniques; Immunoglobulins; Lymphocytes; Lymphoma; Multiple Myeloma; Plasmacytoma

Topics: Acid Phosphatase; Blood Cell Count; Chlorambucil; Fluorescent Antibody Technique; Histocytochemistry; Humans; Hypergammaglobulinemia; Immunoglobulin D; Immunoglobulin E; Immunoglobulin M; Immunoglobulins; Lectins; Leukemia; Leukocytes; Lymphatic Diseases; Lymphocytes; Male; Microscopy, Electron; Middle Aged; Prothrombin Time; Splenomegaly; Technetium; Uric Acid