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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The protective effect of passively administered immunoglobulin has been known for many years. Although its accepted use over the last 40 years has been in the prevention and treatment of infection its widest and, arguably, most important application has been in the prevention of Rhesus haemolytic disease of the newborn. However, the development over the last decade of a number of safe and effective immunoglobulin preparations for intravenous use has allowed its more widespread utilisation in clinically appropriate settings. It is now widely accepted that intravenous immunoglobulin (IVIgG) is indicated, on a repeat basis, as treatment of choice as replacement therapy for patients with primary antibody deficiency. It may also be effective, in the non-immune deficient patient, in the management of certain bacterial as well as viral infections. This is particularly the case in the pre-term neonate but may have an application in the infected intensive care patient. The benefit in these patient groups has led to a re-evaluation of the use of immunoglobulin replacement therapy in the severe secondary antibody deficiency states associated with such haematological conditions as multiple myeloma and chronic lymphocytic leukaemia. These are currently the subject of randomised, controlled studies. The observation that the use of IV IgG may be associated with effects other than passive transfer of antibody were first made by Imbach in Switzerland. While treating children with immunodeficiency he noticed that two with a coincident immune thrombocytopenia had a rapid platelet increment in close association with the immunoglobulin infusion. He subsequently confirmed that this was a rapid and predictable form of therapy in childhood idiopathic thrombocytopenic purpura (ITP) and that in some children it appeared to affect the natural history of the disease. Since these initial observations the response has been confirmed in both children and adults and extended to other immune-based haematological disorders.
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PMID:Clinical use of intravenous immunoglobulin in blood disorders. 305 61

Both membrane (p55) and soluble (p45) forms of TAC-reactive interleukin-2 receptor (IL-2R) are expressed and/or released by activated lymphocytes or monocytes. Previous work has detected increased levels of circulating, TAC-soluble IL-2R (soluble TAC antigen) in the serum of most B-cell chronic lymphocytic leukemia (B-CLL) patients. We detected soluble TAC antigen in B-CLL patients (mean of 3,332 U/mL v 410 for controls). Serum soluble TAC antigen levels increased with stage (mean value of 1,187 U/mL for stage 0 v 2,527 for stage 2 and 5,410 for stages 3 and 4). We next attempted to determine whether the elevated serum levels of soluble TAC antigen in B-CLL patients might result from shedding or secretion of the receptor from the circulating, malignant B cells. Purified, malignant B cells from B-CLL patients were capable of producing easily detectable soluble TAC antigen after 48 hours of in vitro culture (range of 60 to 1,563 U/mL). IL-2R production by CLL B cells was dose dependent in most patients over a concentration of 10 x 10(6) to 60 x 10(6)/mL. In contrast, there was little or no detectable soluble TAC antigen when highly purified T cells from the same patients were cultured. Finally, despite elaboration of soluble IL-2R by CLL B cells, membrane expression of B-cell IL-2R was detected in only six of 11 patients. Thus, the cellular source of the elevated serum IL-2R levels is the malignant CLL B cell. Taken together these data suggest that (a) the malignant CLL B cell is "activated" in terms of release of soluble IL-2R and may serve as a tumor marker in this disease and (b) the elevated levels of circulating IL-2R may be an associated factor in the cellular immunodeficiency noted in B-CLL patients.
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PMID:The malignant B cells from B-chronic lymphocytic leukemia patients release TAC-soluble interleukin-2 receptors. 313 58

We identified 105 patients with lymphoid neoplasia associated with the acquired immunodeficiency syndrome (AIDS) at the New York University Medical Center from 1981 through 1986: 89 had non-Hodgkin lymphoma; 13, Hodgkin disease; and 3, chronic lymphocytic leukemia. Immunophenotypic and antigen receptor gene rearrangement analysis showed the B-cell origin of all non-Hodgkin lymphomas studied and the clonal suppressor-cytotoxic T-cell subset origin of the chronic lymphocytic leukemias. We classified 69% of the non-Hodgkin lymphomas as high grade (small, noncleaved and large cell, immunoblastic-plasmacytoid) and 31% as intermediate grade (diffuse large cell). Each histopathologic category was correlated with distinct clinical features, including a statistically significant difference in median survival. Patients with Hodgkin disease had an atypical, aggressive clinical course, whereas patients with T-cell chronic lymphocytic leukemia had an indolent clinical course. These studies show the clinical, morphologic, and immunophenotypic spectrum of AIDS-associated lymphoid neoplasia, that the natural history of Hodgkin disease is altered in patients with AIDS, and support the Centers For Disease Control's recent revision in diagnostic criteria for AIDS to include intermediate-grade diffuse, aggressive non-Hodgkin lymphomas occurring in patients seropositive for human immunodeficiency virus.
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PMID:Lymphoid neoplasia associated with the acquired immunodeficiency syndrome (AIDS). The New York University Medical Center experience with 105 patients (1981-1986). 335 73

Blood monocytes were analyzed in 28 patients with chronic lymphocytic leukemia without previous cytotoxic therapy and without recent infection. Using monoclonal antibodies and flow cytometry, monocytes identified by LeuM3 or My4 were low in percentage (2.3%), but absolute numbers were increased in many patients with values exceeding the normal range (120 to 510/microliter) in seven of 28 patients. Monocytosis was more prominent in patients with high leukemic counts, but there was no correlation to clinical stages. Monocytopenia was evident with less than 50 LeuM3+ cells/microliter in three patients. Two-color fluorescence was used for the analysis of cell surface expression of major histocompatibility complex (MHC) Class II molecules, complement receptors, and Fc receptors on the LeuM3+ monocytes. Compared to cells from control donors, there was an increase for MHC class II antigens, complement receptors, and Fc receptors on the monocytes in chronic lymphocytic leukemia, in terms of both the percentage of positive cells among the LeuM3+ monocytes and of fluorescence intensity. This increase was not restricted to patients with monocytosis nor were the molecules always upregulated concomitantly. The increase of antigen expression on LeuM3+ monocytes was more than 50% (1.5-fold) in seven of 22 patients for MHC Class II antigens, in seven of 16 patients for complement receptor and in six of 12 patients for Fc receptor. A similar decrease of antigen expression was observed only in one patient for MHC Class II and in one patient for complement receptor expression. Monocytosis and increased expression of monocyte cell surface antigens described for a large portion of patients might be causally involved in the immunodeficiency in chronic lymphocytic leukemia.
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PMID:Abnormal blood monocytes in chronic lymphocytic leukemia. 340 22

Tolerance, clinical effects and kinetics of an unmodified immunoglobulin preparation for intravenous use were investigated in 4 patients with advanced chronic lymphocytic leukemia. Previously, good tolerance of the preparation had been found in 49 immunologically normal patients. The four patients with secondary humoral immunodeficiency received doses of 140-360 mg IgG/kg per infusion as outpatients at monthly intervals. With one exception, no acute infections (pneumonitis), as commonly seen before, were observed during the observation time of 24 to 68 weeks, and the pre-existing chronic infections (bronchitis, sinusitis etc.) remained compensated without antibiotics. In all four patients tolerance of the preparation was good. In all cases of hypogammaglobulinemia a dose-dependent increase in the serum IgG concentration was observed immediately after the infusion. However, persistence of the serum IgG increase showed considerable interindividual differences. The half life of the tetanus and HBs antibodies (21.7 to 34.4 and 19.7 to 25.7 days respectively) found in 4 healthy volunteers is within the biological range. This indicates an unmodified structure of the antibodies of the IgG class contained in the preparation used.
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PMID:[Tolerability and pharmacokinetics of an intravenous immunoglobulin preparation in immunologically normal subjects and tolerability in patients with hypogammaglobulinemia resulting from chronic lymphatic leukemia]. 351 30

The risk of developing a second primary cancer was evaluated in approximately 19,000 persons with initial cancers of the lymphatic and hematopoietic system in Connecticut between 1935 and 1982. Significant excesses for all second cancers were observed among patients with leukemia (34%), Hodgkin's disease (70%), non-Hodgkin's lymphoma (25%), and multiple myeloma (24%). In general, the risk of second cancers was greater in males than in females, even for cohorts not showing an excess of surveillance-related prostate cancer. Among patients with leukemia, significant excesses of cancers of the lung, kidney/ureter, and prostate were noted; cutaneous melanoma was elevated only in males. These excesses did not persist in the small number of long-term survivors. Possible etiologic factors included tobacco smoking for lung and kidney cancers, medical surveillance artifact for prostate cancer, and immunosuppression for malignant melanoma and lung cancer. The large number and good prognoses of patients with chronic lymphocytic leukemia strongly influenced the pattern of second cancers when all leukemias were analyzed together; no evidence was found for an increased risk of second cancer in patients with acute lymphocytic leukemia. A disproportionate number of subsequent cancers, particularly those of the kidney and ureter, were diagnosed incidentally at autopsy. Patients with Hodgkin's disease displayed significant excesses of cancers of the buccal cavity and pharynx, lung, female breast, and thyroid. The latter 3 sites remained significantly elevated in long-term survivors (10 yr or more postdiagnosis), so that radiation therapy may have contributed to their development. Among persons with non-Hodgkin's lymphoma, cancers of the stomach, lung, brain, and connective tissue occurred excessively. The first 3 sites, plus cancers of the urinary bladder, remained elevated among long-term survivors. The brain cancer excess, not previously reported, may represent misclassification of central nervous system lymphoma. The risk of gastric cancer is reminiscent of similar findings in patients with both acquired and genetically determined immunodeficiency disorders. The alkylating agent, cyclophosphamide, used extensively in the treatment of non-Hodgkin's lymphoma, is known to cause bladder cancer in man.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Second cancer following lymphatic and hematopoietic cancers in Connecticut, 1935-82. 408 98

Human T cell hybridomas were generated by several techniques and the supernatants generated were screened for activity on human B cells. Three general activities were noted; B cell proliferation factor ( BCPF ), B cell differentiation factor (BCDF), and an IgA isotype-specific helper factor. BCPF acts on B cells to induce proliferation without differentiation and is distinct from conventional BCGF. This was documented by BCPF 's inability to synergize with anti-mu Ab in a standard BCGF assay ( Muraguchi & Fauci 1982, Howard et al. 1982, Sieckman et al. 1981), as well as its differential effect on a leukemic B cell preparation, when compared with BCGF. A possible schema for BCPF activity is depicted in Figures 3 and 4. In Figure 3, BCPF acts like Ag in vivo or like anti-mu in vitro, pre-activating B cells and rendering them responsive to BCGF. Figure 4 represents what our data depict, that is that BCPF bypasses the response to BCGF and induces cells to proliferate without pre-activation. The difference in the 2 mechanisms may be concentration-dependent and this possibility is currently being evaluated. It is interesting to speculate that T cells in vivo are capable of initiating B cell activation and may account for polyclonal responses seen with some Ag-specific reactions. BCDF(s) act on post-activated B cells (Figure 3) to induce differentiation to Ig-secreting cells. They appear to be heterogeneous and, therefore are capable of inducing varied responses depending on the B cell subpopulation affected. Figure 3 is deliberately complex demonstrating some of the possible as well as documented BCDF activities including polyclonal differentiation and isotype specific activity in IgA committed B cells. We cannot be certain of the frequency of these BCDF-secreting T cells, but the studies of cells from patients with common variable immunodeficiency and chronic lymphocytic leukemia have helped to dissect out these activities. These data would suggest that these BCDF subgroups are important, as deficiencies in one or more subgroups may result in disease.
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PMID:Regulation of B cell activation and differentiation with factors generated by human T cell hybridomas. 623 20

Cell surface marker analyses conducted on human peripheral blood lymphoid cells have proven extremely useful in the diagnosis of immunodeficiency and the diagnosis and staging of malignancies. In this paper we have focused on the ratio of helper to suppressor cells in patients with the acquired immune deficiency syndrome and in patients with malignancy. In thirty-three patients with the acquired immune deficiency syndrome, the majority showed an inverted helper:suppressor ratio, elevated serum thymosin alpha 1, and elevated serum lysozyme levels. The inverted ratio was due to a deficiency in T-helper cells. The inverted helper:suppressor ratio was associated with functional suppressor cell activity that was seen in 12 out of 21 patients examined. Patients' lymphocytes were found to suppress the PHA, pokeweed mitogen, and concanavalin-A responses of normal subjects' lymphocytes. The suppression also correlated with impaired lymphocyte proliferative responses among the patients' cells themselves. Because of these findings, the helper:suppressor ratio was studied in patients with solid tumors, lymphoma, acute leukemia, chronic lymphocytic leukemia, and hairy cell leukemia. Approximately 30% of these patients have an inverted helper:suppressor ratio. However, in ten out of 30 patients with chronic lymphocytic leukemia and in three out of 45 patients with lymphoma, the helper:suppressor ratio was elevated, being greater than 3.0. The significance of these findings is as yet to be explored, but it is suggested that an inverted helper:suppressor ratio in patients with malignancy may relate to an advanced stage of disease or a poor prognosis. Documentation of this point will require further study.
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PMID:Leukocyte subset analysis and related immunological findings in acquired immunodeficiency disease syndrome (AIDS) and malignancies. 623 50

The percentages of lymphocytes subpopulations were assessed in the peripheral blood and bone marrow of B chronic lymphocytic leukaemia patients with monoclonal antibodies and flow cytometry. The absolute number of peripheral T cells is higher compared to healthy subjects; the imbalance of OKT 4 and OKT 8 positive subsets in peripheral blood is characterized by an inversion of the T 4/T 8 ratio. T 4 positive cells are predominant in the bone marrow; the Leu 7 positive population is increased in absolute numbers. These precocious phenomena could be important in the immunodeficiency associated with B CLL and/or in the progression of the disease.
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PMID:Peripheral blood and bone marrow lymphocytes of B chronic lymphocytic leukaemia patients. 633 70

These studies reveal that the enumeration of peripheral blood mononuclear cells by fluorescence microscopy and automated flow microfluorometry show a high degree of correlation whether the cells came from normals, individuals with common variable immunodeficiency, chronic lymphocytic leukemia of B cell origin or chronic lymphocytic leukemia of T cell origin. There was excellent agreement between these two methods when counting positive cells stained by the pan-T monoclonal antibodies OKT3 and Leu-1, the helper T reagents OKT4 and Leu-3a, and the suppressor T antibodies OKT8 and Leu-2a. The values obtained for B cells using a pan-B (HB-2) cell antibody analyzed by fluorescence microscopy and automated flow microfluorometry gave a correlation coefficient of 0.86. The percentage of cells identified by antibodies with reactivities toward peripheral blood monocytes (MMA or Leu-M1), the HLA-DR determinant, and HNK-1 (Leu-7) positive cells gave correlation coefficients of 0.90, 0.90, and 0.80 respectively when compared by the 2 methods mentioned above. These data suggest that comparable values for lymphocyte subpopulations in human blood samples can be obtained using the most convenient and available technology.
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PMID:Enumeration of human lymphocyte subpopulations by immunofluorescence: a comparative study using automated flow microfluorometry and fluorescence microscopy. 660 Nov 63


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