Biomedical subjects

M Santaella

Publications and source records attributed to M Santaella.

9 recordsLinked to original sources

PubMed1997

Sustained response to interferon in a patient with common variable immunodeficiency and hepatitis C.

Hepatitis C infection progresses faster in patients with hypogammaglobulinemia, often leading to death from liver failure within 10 yr of exposure. Response to interferon treatment has been poor in these patients. We report the case of a patient with common variable immunodeficiency and hepatitis C in whom a sustained biochemical and viral remission was obtained after treatment with interferon.

Adult↗

PubMed1986

Immunoregulatory disorders associated with hereditary angioedema. I. Clinical manifestations of autoimmune disease.

Occasional reports have appeared linking hereditary angioedema (HAE) with autoimmune diseases. We have systematically evaluated 157 patients for manifestations of autoimmunity. Nineteen of these patients (12%) had clinical immunoregulatory diseases including glomerulonephritis (five patients), Sjögren's syndrome (three), inflammatory bowel disease (three), thyroiditis (two), systemic lupus erythematosus (one), drug-induced lupus (one), rheumatoid arthritis (one), juvenile rheumatoid arthritis with IgA deficiency (one), incipient pernicious anemia (one), and sicca syndrome (one). All eight patients with HAE who developed an autoimmune disease with a known human histocompatibility antigen association developed a disease associated with their histocompatibility antigen haplotype (p = 0.014). Although only four patients developed Sjögren's syndrome or sicca syndrome, an additional nine manifested part of the sicca complex. We also found patients with HAE with features suggestive of an immune-based abnormality. These features included idiopathic pancreatitis (three patients), Raynaud's disease (two), partial lipodystrophy (one), chronic chorioretinitis (one), and alopecia universalis (one).

Adolescent↗

PubMed1986

Immunoregulatory disorders associated with hereditary angioedema. II. Serologic and cellular abnormalities.

Hereditary angioedema is defined biochemically by a deficiency in the functional activity of the inhibitor of Cl, Cl esterase inhibitor (Cl INH). Deficiency of this regulator of the early classic pathway of complement results in chronic activation of this cascade with a resultant deficiency of C4 and C2. Ninety-seven patients with either complicated (associated with autoimmune disorders) or uncomplicated hereditary angioedema were evaluated for laboratory evidence of immunoregulatory defects. Specific cellular and humoral abnormalities were found and included increased mean total lymphocyte counts, increased mean Leu 4+ (total) and Leu 3+ (helper) T cells, an increased mean Leu 3/Leu 2 (helper/suppressor T cell) ratio, polyclonal B cell activation, and evidence of circulating immune complexes. C4 functional titers were negatively correlated with percent Leu 3+ cells and absolute Leu 3+ cell numbers. We failed to detect any evidence of immune deficiency in this population, and yet a statistically significant number of patients demonstrated elevated levels of antibodies to Epstein-Barr virus antigens when patients were compared to a control group. Thus, early classic complement pathway activation and/or partial complement component deficiency may effect T cell subpopulations and B cell activation. However, additional predisposing factors (e.g., genetic or viral) appear necessary for the development of a particular autoimmune disease in hypocomplementemic patients.

Adolescent↗

PubMed1983

Cleavage of membrane-bound C3b and C3bi by viable human neutrophils (PMN).

Cleavage of C3 by purified leukocyte enzymes and crude extracts of human polymorphonuclear leukocyte (PMN) granules has been reported. We demonstrate that viable PMN mediate the cleavage of erythrocyte-bound C3b and C3bi via cell-associated proteases. Greater than 50% of 125IC3(x) was released from EAC43bix during a 5-min incubation with viable PMN at 37 degrees C. More than a 30-min incubation was required for substantial release from EAC43bx. Culture fluids from PMN suspensions had limited cleaving ability; cleavage of cell-bound C3bx and C3bix was only partially reduced when PMN were preincubated with high levels of soluble C3 which completely blocked EAC43b rosettes. Thus, cell-to-cell contact between opsonized erythrocytes and viable PMN with surface-associated proteases are responsible for cleavage of these opsonic sites. The effect of defined protease inhibitors on PMN cleaving activity as well as on purified leukocyte elastase was examined. Phenylmethylsulfonyl fluoride (PMSF) and the leukocyte elastase inhibitor, methoxy-succinate-alanine-alanine-valine-chloromethyl ketone (MeO) each inhibited cleavage of C3b by 90% and C3bi by 60%. In contrast, the cathepsin-G inhibitor, benzyloxy-carbonyl-glycine-leucine-phenylalanine-chloromethyl ketone (Z) inhibited C3b and C3bi cleavage by less than 20 and less than 5%, respectively. Ethylenediaminetetra-acetate (EDTA), which had a minimal effect on soluble leukocyte elastase, also inhibited PMN-related release. Thus, elastase appeared to be the principle but not the only enzyme responsible for cleavage of C3b and C3bi. PMSF and MeO had a minimal effect on the activity of purified C3bINA (Factor I); and PMN-mediated release of C3b fragments was not inhibited by anti-Factor I and anti-beta 1H (Factor H) IgG and Fab. Thus, these control proteins are not involved in the PMN-mediated cleavage under study. PMN-mediated cleavage of C3b was also inhibited when PMSF- and MeO-treated PMN were washed to remove the fluid phase phase protease inhibitor before adding EAC43b. This suggests that proteases localized in the PMN membrane, prior to the adherence of EAC43b, are responsible for C3b cleavage. Normal human serum was effective in blocking PMN-mediated release activity, while serum from alpha 1 antitrypsin-deficient patients was minimally effective. This suggests a mechanism for the in vivo regulation of PMN-mediated release of C3b and C3bi from opsonized particles by the natural plasma protease inhibitors.

Amino Acid Chloromethyl Ketones↗

PubMed1983

Complement receptor expression by neoplastic and normal human cells.

Complement receptor (CR) expression in cell lines derived from Burkitt's lymphoma (BL), Epstein Barr virus-transformed cord blood lymphocytes (CB), and peripheral lymphocytes from patients with infectious mononucleosis (IM) was examined. Red cell intermediates bearing various densities of C4b, C3b, C3bi, or C3d were tested for rosette formation with the cell lines. In addition, a series of studies was performed under conditions that precluded the cleavage of cellbound C3b by Factor I (C3bINA). These conditions did not alter rosetting by the cells that were tested. RAJI cells rosetted with EAC3bi greater than EAC3d greater than EAC3b, but not with EAC4b. EAC3b/RAJI rosette formation required much greater quantities of C3b bound to red cells than did CB and IM lines, which unlike RAJI, also bound EAC4b. All of the BL lines failed to bind EAC4b even at a C4b density of 50,000 molecules/cell, but several lines did form rosettes with EAC3b, and most formed rosettes with EAC3bi and EAC3d. Fluid phase C3b blocked RAJI/EAC3b rosetting while having little effect on RAJI/EAC3bi rosette activity. Moreover, fluid phase C3b, as well as C4b, blocked RAJI/EAC3b rosettes more effectively than CB/EAC3b rosettes. The results indicate that the RAJI cell line has a receptor for C3b, with characteristics that differ markedly from the C3b receptor of cell lines derived from CB lymphocytes and of lymphoblastoid cell lines derived from patients with IM. This receptor is capable of interacting with soluble but not cellbound C4b. In these studies, rosette formation was examined under various ionic conditions. RAJI/EAC3b rosette formation was severely reduced as ionic strength was increased, whereas RAJI/EAC3bi binding was only moderately decreased at physiologic ionic strength. In striking contrast, EAC3bi binding to monocytes, PMN, and human erythrocytes was markedly reduced as ionic strength increased, but EAC3b binding to these cells was less sensitive to changes in ionic strength. Under conditions of physiologic ionic strength, the C3bi receptor of phagocytic cells may be at a functional disadvantage in the binding of C3bi-coated particles. This may have major physiologic implications.

Burkitt Lymphoma↗

PubMed1981

Binding of immunoglobulin- and complement-coated erythrocytes to human neutrophil subpopulations.

Human neutrophils are separable into two populations on the basis of the presence or absence of Fc receptors as detected by rosette assays with IgG antibody-sensitized human erythrocytes. In the present report it was shown that IgG-sensitized sheep erythrocytes could detect some Fc receptor activity on those cells which are Fc receptor-negative with the human cell assay. There was clearly a difference between Fc receptor expressed on the positive and negative cells. Neutrophils with "high" and "low" density Fc receptor activity were studied for a range of membrane receptors for complement fragments including, C4b, C3b, C3d, and C3bi. No difference was found between the two populations of cells in their expression of complement receptors. Moreover, neither population expressed receptors for C3d, suggesting that neither population was a high proportion of immature neutrophils.

Animals↗

PubMed1981

Induction of complement receptor expression in cell lines derived from human undifferentiated lymphomas. II. Characterization of the induced complement receptors and demonstration of the simultaneous induction of EBV receptor.

We have studied the specificity of complement receptors induced by theophylline in 2 cell lines derived from undifferentiated lymphomas, one of Burkitt's type, and compared it to that of complement receptors in other cell types. Both C3b and C3d receptors were induced. The induced C3b receptor differed from the C3b receptor of mature normal lymphocytes, polymorphonuclear leukocytes and the cells of a nodular lymphoma in 2 respects. Firstly, it bound C3b much less avidly (by a factor of several hundred-fold) and secondly, we were unable to demonstrate C4b binding. EBV receptors were induced at the same time as complement receptors, and permitted the conversion of a greater fraction of cells to EBNA positivity after experimental infection with EBV. The induction of receptors was not associated with a change in the fluidity of the plasma membranes and our data do not favor a different orientation of induced receptors within the membrane as compared to receptors of other cell types--a potential explanation for the different specificities. Our findings are consistent with the possibility that the complement receptors of lymphocyte precursors differ from these of mature lymphocytes.

Binding, Competitive↗

PubMed1980

Replacement therapy in hereditary angioedema: successful treatment of acute episodes of angioedema with partly purified C1 inhibitor.

Although considerable progress has been made during the past two decades in the use of androgens to prevent attacks of hereditary angioedema, replacement of the deficient C1-inhibitor protein would provide a useful menas of treatment once an attack has begun. We studied the clinical use of C1 inhibitor that was partly purified on a large scale from pooled plasma. The in vivo efficacy and safety of this protein concentrate were evaluated during 11 intravenous infusions in eight patients with hereditary angioedema. Three patients received the C1-inhibitor preparation during an asymptomatic period. Increases in serum C4 activity provided evidence of the biologic activity of the infused inhibitor. Intravenous administration of the concentrate during acute abdominal or laryngeal attacks of hereditary angioedema in five patients resulted in abatement of symptoms in addition to increased serum C4 activity. No untoward effects of the intravenous administration of the C1 inhibitor were observed in these eight patients. Thus, this C1-inhibitor preparation seems to offer the potential for safe, effective replacement therapy and may provide a means of controlling an attack of hereditary angioedema that is in progress.

Angioedema↗

PubMed1980

Characterization of lymphoma-derived cell lines: comparison of cell lines positive and negative for Epstein-Barr virus nuclear antigen. II. Surface markers.

Fifteen of 16 lymphoma-derived cell lines and the Faji and P3HR1 cell lines were characterized with regard to certain surface markers, particularly immunoglobulins, complement receptors, Epstein-Barr virus (EBV) receptors, and Fc receptors. Ten lines positive for EBV nuclear antigen (EB-pos) were stained weakly or not at all by antihuman immunoglobulin fluorescein isothiocyanate conjugates, whereas EBV nuclear antigen negative (EB-neg) cell lines stained brightly. EB-pos lines frequently manifested Fc receptors, particularly for 7S antibody, whereas EB-neg lines did not. Receptors for the C3b component of complement and for EBV, which correlated significantly with each other, were expressed to a much lesser extent by EB-neg lines than by EB-pos lines. These findings are pertinent to an understanding of the infrequent association of this virus with American undifferentiated lymphomas of the Burkitt's and non-Burkitt's types.

Antigens, Viral↗