Robert L. Longmire

In Vitro Platelet Phagocytosis by Splenic Leukocytes in Idiopathic Thrombocytopenic Purpura

Abstract The ability of splenic leukocytes from 12 patients with idiopathic thrombocytopenic purpura to phagocytose normal, labeled homologous platelets was determined with an in vitro assay technic. The degree of in vitro platelet phagocytosis by these splenic cells correlated inversely with the clinical response to corticosteroids. Mean (± S.D.) per cent leukocyte phagocytic activity from five control spleens was 17.6 ± 5.3. Splenic cells, from four purpuric patients showing no response and five with a partial response to corticosteroids, demonstrated accelerated in vitro phagocytosis, with mean values of 50.6 ± 17.8 and 38.5 ± 17 per cent, respectively; cells from three patients responding completely to corticosteroids had phagocytic values within the normal range of 18.0 ± 2.4 per cent. Platelet phagocytosis by washed splenic cells occurred in the absence of added patient plasma, suggesting concurrent antiplatelet antibody production. These results provide evidence that the spleen is a site of both pl...

Quantitation of Platelet-Binding IgG Produced in Vitro by Spleens from Patients with Idiopathic Thrombocytopenic Purpura

Abstract Although the presence of antiplatelet antibody in idiopathic thrombocytopenic purpura is generally accepted, information on the quantity synthesized, the production site (or sites), and th...

Immunoglobulin Synthesis in Vitro by Splenic Tissue in Idiopathic Thrombocytopenic Purpura

Abstract Experimental and clinical observations suggest that platelet destruction in idiopathic thrombocytopenic purpura (ITP) is due to the production of an antibody against autologous platelets. The origin of antibody synthesis is unknown although the spleen has been considered one likely possibility. When we determined immunoglobulin (Ig) synthesis in vitro by human splenic tissue, mean Ig production by spleens from patients with ITP was five times greater than that of unstimulated control tissue, but was similar to the degree of Ig synthesis by control tissue after in vitro antigenic stimulation. Immunoglobulins produced by one ITP spleen showed binding to autologous and homologous platelets. These data suggest that the spleen in ITP is involved in a humoral response to some antigen. Whether this increased Ig production is directed toward platelet-associated antigens cannot be definitely stated although preliminary findings are suggestive.

In Vitro Splenic IgG Synthesis in Hodgkin's Disease

Abstract Experimental and clinical observations suggest increased lymphoid reactivity in Hodgkins disease. Since thymus-dependent lymphocyte function is often depressed whereas serum antibody responses appear normal, in vitro splenic IgG synthesis was studied to assess B lymphocyte activity. Increased total splenic IgG synthesis occurred in 20 of 22 patients with Hodgkins disease. Mean IgG production by uninvolved and lightly involved spleens of the patients was five and 11 times normal, whereas heavily involved spleens averaged twice normal levels. Unstimulated IgG synthesis by uninvolved and lightly involved spleens of patients was similar to that of normal spleens after secondary antigenic stimulation, suggesting an in vitro response to an in vivo antigenic challenge. When IgG produced in culture by spleens affected by Hodgkins disease was incubated with homologous lymphocytes, highly significant IgG binding levels were found. These data suggest that the spleen in Hodgkins disease responds with a h...

Thrombocytopenia associated with gold therapy: Observations on the mechanism of platelet destruction

Severe thrombocytopenia developed in a patient with rheumatoid arthritis during gold therapy. Increased numbers of marrow megakaryocytes, shortened 51Cr-labeled platelet survival and platelet phagocytosis by splenic macrophages indicated that thrombocytopenia was due to excessive platelet destruction. Aurothiomalate disodium antigenicity was demonstrated by increased lymphocyte blastogenesis, and accentuation of blood and splenic leukocyte migration in the presence of the gold salt. In vitro splenic immunoglobulin G (IgG) production was markedly increased, and a significant portion of the culture-produced IgG attached specifically to homologous platelets and platelet membranes. Serum antiplatelet antibodies could not be demonstrated, nor could it be shown that gold enhanced the binding of splenic-synthesized IgG to platelets. The data indicate an immunologic mechanism for gold-associated thrombocytopenia and permit speculation as to possible ways in which unidentified antigens may be involved in the pathogenesis in idiopathic thrombocytopenic purpura.

Major activity of cladribine in patients with de novo B-cell prolymphocytic leukemia.

PURPOSE De novo B-cell prolymphocytic leukemia (B-PLL) is a distinct clinicopathologic entity usually characterized by marked lymphocytosis, massive splenomegaly, an aggressive course, and refractoriness to therapy. Cladribine (2-chlorodeoxyadenosine [2-CdA]; Ortho Biotech, Raritan, NJ) is a newer purine analog with potent activity against indolent lymphoproliferative disorders. PATIENTS AND METHODS We treated eight patients with cladribine 0.1 mg/kg/d for 7 days by continuous infusion or 0.14 mg/kg/d over 2 hours for 5 days, every 28 to 35 days, for a median of three courses (range, two to five). There were five men and three women, with a median age of 62 years and a median pretreatment duration of 6 months; four patients were previously untreated. RESULTS All eight patients were assessable: five achieved a complete response with a median response duration of 14 months (range, 1+ to 55+), and three achieved a partial response with a median duration of 3 months (range, 1 to 3). Of four patients who achieved a complete response and in whom a peripheral-blood immunophenotypic analysis was performed, two had no circulating B-PLL cells and one had no residual disease on Southern blot analysis. Myelosuppression and infection were the major toxicities: three patients developed grade 3 or 4 myelosuppression, four had bacterial infections, and two had herpes zoster infections. CONCLUSION In this small study of patients with de novo B-PLL, cladribine was an active agent that induced a high overall and complete response rate. These results require confirmation in larger numbers of B-PLL patients.

Different Antiplatelet Antibody Specificities in Immune Thrombocytopenic Purpura

SUMMARY It is generally accepted that patients with immune thrombocytopenic purpura (ITP) produce antibody against platelet‐associated antigens; however, it is not known if these antiplatelet antibodies are directed towards the same or different antigenic sites. In the present studies, quantities of antiplatelet antibody from different ITP patients, sufficient to saturate platelet antigenic sites, were simultaneously incubated with normal platelets and the quantity of platelet‐binding IgG (PBIgG) was determined. In each of the five comparisons made, the amount of PBIgG bound after incubation of normal platelets with saturating quantities of two ITP antibodies approximated to the sum of the PBIgG bound after incubation with the antibodies separately. These data suggest that the antiplatelet antibody from these ITP patients differed in antigenic specificity.

Antibody-dependent lymphocytotoxicity induced by immunoglobulin G from Hodgkin's disease splenic lymphocytes.

Immunoglobulin G, produced in cultures of splenic lymphocytes obtained from patients with Hodgkins disease, bound to a population of homologous peripheral blood lymphocytes and initiated antibody-dependent cell cytotoxicity in cultures from five out of eight patients. Two patients whose cultures produced negative results had minimal disease; the other was in remission. The target cells appear to be T lymphocytes; the effector cells bear Fc receptors that are inhibited by antigen-antibody complexes. Antibody-dependent cell cytotoxicity events may produce the anergy and lymphopenia often seen in Hodgkins disease.

Polycythemia: Erythrocytosis and Erythremia

Abstract A classification of polycythemia and three cases of demonstrating increased red cell mass are presented. Polycythemia may be relative or absolute, secondary to underlying disease, or an id...

An analysis of the immunological specificity of antiserum against human IgG F(ab)2

Inhibition of the interaction between 131I human Fab and a standard dilution of rabbit anti-human F(ab)2, as measured in the ammonium sulfate technique, has been utilized to study and quantitate differences in antigenic determinants associated with pooled IgG, isolated IgG from normal individuals, IgG myeloma proteins of the four known subclasses and IgA and IgM paraproteins. Isolated IgG from four normal individuals was as effective as pooled IgG as an inhibitor of the standard anti-F(ab)2-131I Fab system, indicating that the inhibition system may be used to quantitate small amounts of normal IgG, assuming a normal distribution of K and λ light chains. When K and λ type IgG paraproteins of the four known subclasses were assayed as inhibitors, the K type paraproteins were more effective than the λ type paraproteins. However, the two were additive when mixed in the proportion of 23 K and 13 λ. When K and λ type IgA and IgM paraproteins were used in the inhibition system, neither were as effective as IgG; however, the K type paraproteins were more effective as inhibitors than the λ type. The mixture of 23 K and 13 λ IgA and IgM paraproteins were not additive but instead were dilutional. The test offers a sensitive method for studying antigenic determinants of protein molecules, previously evaluated only by the precipitation reaction or hemagglutination.