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PubMed1988

Anti-Rous sarcoma response of major histocompatibility (B) complex haplotypes B23, B24 and B30.

Responses to Rous sarcoma virus (RSV) induced tumours were studied in UNH 105, a non-inbred line of New Hampshire chickens. Six single male matings encompassing a total of 50 dams produced 345 progeny which segregated for B complex genotypes B23/B23, B23/B24, B23/B30, B24/B24, B24/B30 and B30/B30. Six-week-old chicks were wingweb inoculated with a pseudotype of Bryan high titre Rous sarcoma virus, BH RSV (RAV-1). Tumours were scored for size six times over a 10-week period post-inoculation. Each chick was assigned a tumour profile index (TPI) as an indicator of immunological response. The number of days to death (DTD) was recorded for 148 chicks with terminal tumours. Genotypes B23/B23, B23/B24 and B23/B30, with TPIs of 1.8, 1.7 and 2.0 respectively, did not differ significantly from each other, suggesting dominance of response of B23 over B24 and B30 haplotypes. B24/B30 chicks with the highest TPI (3.4) and shortest DTD (34.6) were significantly different from B30/B30 (2.8; 41.6) but not from B24/B24 (3.1; 34.9) suggesting dominance of response of the B24 haplotype over B30 in the absence of B23.

Animals↗
PubMed1990

Comparative study of hemolytic substances produced by coagulase-negative Staphylococcus strains.

Hemolytic substances H7, H62, and E56, produced by Staphylococcus haemolyticus 7 and 62 and S. epidermidis 56, respectively, were purified. H7 and H62 are probably similar on the basis of their isoelectric focusing profiles in 8 M urea and complete immunological identity as revealed by immunodiffusion with rabbit anti-H7 and anti-E56 sera. For E56, we observed seven bands instead of three in isoelectric focusing and only partial immunological identity with H7 and H62. However, H7 and E56 were similar with regard to the following characteristics: hemolytic spectra against different erythrocytes, kinetics of erythrocyte lysis, heat stability, and inhibition by phosphatidylcholine. E56 was not active at a temperature lower than or equal to 25 degrees C, and its activity increased more rapidly with increased temperature compared with H7. For both substances, the complexes obtained by molecular filtration on Ultrogel AcA54 and the purified peptides by reverse-phase high-pressure liquid chromatography showed some hemolytic activity. These results suggest that a particular association or the presence of a given peptide could enhance the activity.

Chromatography, High Pressure Liquid↗
PubMed2000

Type I and type II T cell profiles in chronic myelogenous leukemia.

T cell immunity is considered to play an important role in the control of cell growth in chronic myelogenous leukemia (CML) although information regarding the characteristics of T lymphocytes in CML patients is limited. Using flow cytometric analysis of intracellular cytokine expression at the single-cell level, we analyzed helper T and cytotoxic T subsets in 8 CML patients. The percentage of interferon-gamma (IFN-gamma) single-positive CD4 cells (Th1) and that of interleukin-4 (IL-4) single-positive CD4 cells (Th2) was markedly decreased in pretreated CML patients compared to normal controls. In addition, the percentage of IFN-gamma/IL-4 double-positive CD4 cells (Th0) was also reduced. Consequently, the percentage of IFN-gamma/IL-4 double-negative CD4 cells was markedly increased. Similarly, a reduction in IFN-gamma single-positive CD8 cells (Tc1) and IFN-gamma/IL-4 double-positive CD8 cells (Tc0) and an increase in IFN-gamma/IL-4 double-negative CD8 cells were observed in pretreated CML patients. Imbalance of these parameters was markedly improved following cytoreduction therapy. Our findings directly indicate anergic states in CML patients. Determination of the factors that affect Th and Tc profiles may lead to further understanding of immunological states and the development of effective immunotherapy.

Adult↗
PubMed2002

Sudden sensorineural hearing loss: supporting the immunologic theory.

Sudden deafness constitutes a diagnostic challenge. Classically, 2 causes, viral and vascular, are considered in the origin of idiopathic sudden hearing loss. More recently added to the list of possibilities are rupture of the membranous labyrinth and immune-mediated sensorineural hearing loss. The latter can be either primary and localized to the inner ear or, in perhaps fewer than one third of cases, secondary to generalized systemic autoimmune disease. The purpose of the present review is to define immune-mediated sudden sensorineural hearing loss as a distinctive entity, on the basis of clinical, immunologic, and pathological findings, and suggest a profile of the typical patient.

Adrenal Cortex Hormones↗
PubMedDate not supplied

Circulating immune complexes in human breast cyst fluids: relationship with intracystic immunoglobulin and electrolyte levels.

Circulating immune complexes, the major classes of immunoglobulins and electrolyte concentrations were measured in sixty-two breast cyst fluids aspirated in women affected by gross cystic breast disease. Two main classes of cysts were defined according to the Na/K ratio. Appreciable levels of immunoglobulins were found in almost all samples examined; 66% of breast cyst fluids showed increased levels of immune complexes. A highly significant linear correlation between increased values of immune complexes and immunoglobulin M (p less than 0.001) was found in apocrine cysts, characterized by Na/K ratio less than 3. However, a significant inverse linear correlation was found between positive values of immune complexes and lowered levels of immunoglobulins A (p less than 0.001) and G (p less than 0.001) in epithelial cysts with Na/K ratio greater than 3. These data suggest and confirm that the menstrual cycle can also influence or modulate the metabolic activity of human breast cells as a part of the secretory immune system. The relationship between immune complexes and immunoglobulins and electrolyte profiles may provide further knowledge about the immunological features of breast cyst fluid and suggest the possible alteration of immune-response in cystic breast lesions associated with increased cancer risk.

Adult↗
PubMed2002

Systemic lupus erythematosus in three ethnic groups. XII. Risk factors for lupus nephritis after diagnosis.

The purpose of this study was to determine the cumulative incidence of lupus nephritis (LN) and the factors predictive of its occurrence in a multiethnic systemic lupus erythematosus (SLE) cohort. We studied 353 SLE patients as defined by the American College of Rheumatology (ACR) criteria (65 Hispanics, 93 African-Americans and 91 Caucasians). First, we determined the cumulative incidence of LN in all patients. Next, we determined the predictors for LN in those with nephritis occurring after diagnosis. The dependent variable, LN, was defined by: (1) A renal biopsy demonstrating World Health Organization (WHO), class II-V histopathology; and/or (2) proteinuria > or = 0.5 g/24 h or 3+ proteinuria attributable to SLE; and/or (3) one of the following features also attributable to SLE and present on two or more visits, which were performed at least 6 months apart--proteinuria > or = 2+, serum creatinine > or = 1.4 mg/dl, creatinine clearance < or = 79 ml/min, > or = 10 RBCs or WBCs per high power field (hpf), or > or = 3 granular or cellular casts per hpf. Independent variables assessed at diagnosis, and if absent, at baseline, were from four domains: sociodemographic, clinical, immunologic and immunogenetic (including the complete antibody profile and MHC class II alleles), and health habits. Variables with P < 0.05 by chi square analyses were entered into domain-specific stepwise logistic regression analyses controlling for disease duration, with LN as the dependent variable. Significant domain-specific regression variables (P < or = 0.1) were then entered into an overall model. The cumulative incidence of LN was 54.3% in all patients, and 35.3% for those developing LN after diagnosis. LN after diagnosis occurred in 43.1% of 65 Hispanics, 50.5% of 93 African-Americans, and 14.3% of 91 Caucasians, P < 0.0001. The duration of follow-up for those with LN after diagnosis was 5.5+/-2.4 vs 4.0+/-2.9 years for those without LN. Hispanic (odds ratio (OR) = 2.71, 95% confidence limits (CL) = 1.07-6.87, P < 0.04) and African-American ethnicities (OR = 3.13, 95% CL = 1.21-8.09, P < 0.02), not married or living together (OR = 3.45, 95% CL = 1.69-7.69, P < 0.0003), higher SLAM score (OR = 1.11, 95% CL = 1.02-1.19, P < 0.007), anti-dsDNA (OR = 3.14, 95% CL = 1.50-6.57, P < 0.0001) and anti-RNP (OR = 4.24, CL = 1.98-9.07, P < 0.0001) antibodies were shown to be significant predictors of the occurrence of LN. Repeated analyses excluding the patients with missing HLA data showed that absence of HLA-DQB1*0201 was also a significant predictor for the occurrence of LN (OR = 2.34, CL = 1.13-5.26, P < 0.04). In conclusion, LN occurred significantly more often in Hispanics and African-Americans with SLE. Sociodemographic, clinical and immunologic/immunogenetic factors seem to be predictive of LN occurring after the diagnosis of SLE has been made.

Black or African American↗
PubMed2001

Lipid and acute-phase protein alterations in HIV-1 infected patients in the early stages of infection: correlation with CD4+ lymphocytes.

Lipid and acute-phase protein alterations have been described in various infection diseases, and they have been recorded during the early stages of HIV infection. Lipid and acute-phase protein profiles also have been correlated with cellular immunological abnormalities. To document these correlations during HIV infection, we studied 75 HIV-infected patients and 26 HIV-negative controls. Patients were classified according to the criteria proposed by the Walter Reed Army Institute: as WR-1 (CD4 lymphocytes, 1154 +/- 268/mm3), WR-2 (CD4, 793 +/- 348/mm3) and WR3/4 (CD4, 287+/-75 mm3). Triglycerides, total cholesterol and HDL-cholesterol concentrations were measured by enzymatic methods. Immunoglobulins (IgA and IgG) and acute-phase proteins (haptoglobin, alpha1-acid glycoprotein, C-reactive protein and transferrin) were determined by immunonephelometry. Haptoglobin levels were significantly increased in HIV-positive patients and correlated with the progression of HIV-infection (control<WR1<WR2<WR3/4). WR-2 and WR-3/4 patients had lower total cholesterol, HDL-cholesterol, and albumin concentrations, however, alpha1-acid glycoprotein and IgA levels were higher, when compared to HIV-negative controls. Elevated triglyceride levels (1.51+/-0.75 mmol/L) were found only in WR3/4 patients, when compared to the control individuals (1.05+/-0.04 mmol/L). No differences were found in transferrin and C-reactive protein concentrations among the studied groups. CD4+ lymphocyte counts were inversely correlated with triglycerides, IgA, alpha1-acid glycoprotein and haptoglobin, and they were positively correlated with albumin, total cholesterol and HDL-cholesterol. Multiple linear regression analysis showed that increased haptoglobin and IgA levels were the best predictive variables of a decreasing CD4+ lymphocyte count. In conclusion, our data showed that: 1) a decrease in total cholesterol, HDL-cholesterol and albumin levels occurred earlier than hypertriglyceridemia in the course of HIV infection; 2) increased levels of haptoglobin occurred earlier than that of alpha1-acid glycoprotein and IgA; 3) haptoglobin and IgA were the best predictive variables of a decreasing CD4+ lymphocyte count. Decreases in HDL-cholesterol and albumin levels with increases in haptoglobin, alpha1-acid glycoprotein, IgA, and triglycerides levels are indications of disease progression in HIV-infected patients.

Acute-Phase Proteins↗
PubMed2001

Role of dendritic cell-derived cytokines in immune regulation.

Over the last several years, it has become increasingly clear that dendritic cells (DC) are not only critical for the initiation of T cell immunity, but these cells also determine the course of the subsequent immune response (i.e. tolerance vs. immunity, Th1 vs. Th2). However, the mechanisms by which DC can influence the final outcome of a given immune response remain to be understood. Currently, the ability of DC to direct immunity has been linked to: (1) hematopoeitic lineage, (2) maturation stage, and (3) environmental stimuli. While the literature supports each possibility, one common feature of all three hypotheses is that immunological outcome is directly correlated to the profile of DC-derived cytokines. A review of the existing scientific literature strongly suggests that the capacity of DC to orchestrate the immune responses is not an intrinsic quality of the cell, but rather it is the result of environmental stimulation which is reflected in their cytokine and chemokine production.

Cell Communication↗
PubMed1995

Cytogenetics of hybrid acute leukemias.

Although the recognition of hybrid acute leukemia (HAL) is still controversial, several reports have described cytogenetic findings in these leukemias over the last 3 years. A distinct chromosomal profile appears to be associated with different immunologic subsets of HAL. The classical t(15;17), and inv(16) as well as abnormalities of the long arm of chromosome 5 and/or 7 are preferentially associated with acute myeloid leukemia (AML) with T-cell features; the t(8;21)(q22;q22), the Ph chromosome, and 11q23 rearrangements are more frequently found in AML with B-cell features; the Ph chromosome, t11q23 and 14q32 breaks without rearrangements of the immunoglobulin heavy chain gene may be associated with acute lymphoblastic leukemia (ALL) with myeloid markers. In addition, some chromosome aberrations may be encountered more frequently in acute leukemia with major phenotype deviations than in unselected cases of acute leukemia: namely the Ph chromosome, 11q23 rearrangements, and +13. These chromosome changes appear to be associated with a low complete remission (CR) rate. An association has been documented in some patients with ALL between the presence of the t(9;22) and a minor myeloid component consisting of 5-15% blast cells with myelomonocytic features, raising the possibility that a diagnosis of bilineal acute leukemia would be more appropriate in such cases. These patients appear to have a severe outcome with significantly lower CR rate than similar cases of Ph-positive ALL without a minor myeloid component.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed2026

Pre-treatment T cell features and immune-milieu characteristics shape treatment-induced exhaustion and resistance to Blinatumomab in B-cell acute lymphoblastic leukemia.

BACKGROUND: Blinatumomab (Blina), a CD19&#xd7;CD3 bispecific T cell engager, is approved for the treatment of B-cell precursor acute lymphoblastic leukemia (BCP-ALL), yet resistance remains a major challenge and the mechanisms driving treatment failure remain poorly understood. METHODS: To define the immunological determinants of resistance, we performed longitudinal profiling of peripheral blood T cells and the immune milieu of 34 patients receiving Blina using flow cytometry (n=19), single-cell CITE-seq (n=13), ex vivo Blina-induced cytotoxicity (n=26) and serum proteomics (n=17). RESULTS: At baseline, Responders (R) were enriched for CD8+ effector memory T cells (TEM) expressing higher levels of cytotoxic genes and their transcriptional regulator ZNF683. Conversely, CD8+ TEM from Non-Responders (NR) displayed transcriptional features of activation without proportionate cytotoxic commitment. Over the course of the first treatment cycle, NR exhibited a progressive expansion of TIM3+CD8+ T cells that correlated with a rapid loss of ex vivo cytotoxic function. Linking baseline state to post-treatment T-cell exhaustion, the magnitude of TIM3+CD8+ expansion correlated inversely with baseline ZNF683 expression in CD8+TEM. Beyond T-cell-intrinsic features, NR harbored an immunosuppressive milieu characterized by higher circulating levels of M2-polarizing factors (CSF-1, HGF) and the TIM-3 ligand Galectin-9, which correlated positively with the magnitude of TIM3+CD8+ T-cell expansion. CONCLUSIONS: These findings indicate that post-Blina CD8+ T-cell exhaustion is associated with resistance and it is shaped by both reduced ZNF683-dependent cytotoxic programming in CD8+ TEM and an immunosuppressive milieu. This provides a rationale for risk stratification based on baseline transcriptional profiling of CD8+ TEM and for combinatorial strategies targeting the suppressive microenvironment.

Humans↗
PubMed1999

An inherited disorder of lymphocyte apoptosis: the autoimmune lymphoproliferative syndrome.

The autoimmune lymphoproliferative syndrome (ALPS) affords novel insights into the mechanisms that regulate lymphocyte homeostasis and underlie the development of autoimmunity. This syndrome arises early in childhood in persons who inherit mutations in genes that mediate apoptosis, or programmed cell death. The timely deletion of lymphocytes is a way to prevent their accumulation and the persistence of cells that can react against the body's own antigens. In ALPS, defective lymphocyte apoptosis permits chronic, nonmalignant adenopathy and splenomegaly; the survival of normally uncommon "double-negative" CD3+ CD4- CD8- T cells; and the development of autoimmune disease. Most cases of ALPS involve heterozygous mutations in the lymphocyte surface protein Fas that impair a major apoptotic pathway. Detailed immunologic investigations of the cellular and cytokine profiles in ALPS show a prominent skewing toward a T-helper 2 phenotype; this provides a rational explanation for the humoral autoimmunity typical of patients with ALPS. Prospective evaluations of 26 patients and their families show an ever-expanding spectrum of ALPS and its major complications: hypersplenism, autoimmune hemolytic anemia, thrombocytopenia, and neutropenia. Defective apoptosis may also contribute to a heightened risk for lymphoma.

Apoptosis↗
PubMed2001

Immune and clinical responses in patients with metastatic melanoma to CD34(+) progenitor-derived dendritic cell vaccine.

Immunization to multiple defined tumor antigens for specific immune therapy of human cancer has thus far proven difficult. Eighteen HLA A*0201(+) patients with metastatic melanoma received injections s.c. of CD34(+)progenitor-derived autologous dendritic cells (DCs), which included Langerhans cells. DCs were pulsed with peptides derived from four melanoma antigens [(MelAgs) MelanA/MART-1, tyrosinase, MAGE-3, and gp100], as well as influenza matrix peptide (Flu-MP) and keyhole limpet hemocyanin (KLH) as control antigens. Overall immunological effects were assessed by comparing response profiles using marginal likelihood scores. DC injections were well tolerated except for progressive vitiligo in two patients. DCs induced an immune response to control antigens (KLH, Flu-MP) in 16 of 18 patients. An enhanced immune response to one or more MelAgs was seen in these same 16 patients, including 10 patients who responded to >2 MelAgs. The two patients failing to respond to both control and tumor antigens experienced rapid tumor progression. Of 17 patients with evaluable disease, 6 of 7 patients with immunity to two or less MelAgs had progressive disease 10 weeks after study entry, in contrast to tumor progression in only 1 of 10 patients with immunity to >2 MelAgs. Regression of >1 tumor metastases were observed in seven of these patients. The overall immunity to MelAgs after DC vaccination is associated with clinical outcome (P = 0.015).

Adult↗
PubMed2004

[A change of immune profile of patients with schizophrenia during treatment].

Cellular and humoral immunological parameters have been studied in 59 schizophrenic patients and 38 healthy controls. Immunological indices (CIC, autoantibodies to cardiolipin) were found to be significantly elevated in patients in the acute disease stage before the treatment. After olanzapin therapy, a level of these parameters decreased and did not differ from that of controls. In patients, irrespective of clinical condition and treatment, functional activity of immunocompetent cells (phagocyte activity of neutrophils and monocytes, cytotoxic activity of lymphocytes natural killers, interleukin-2, interleukin-10 and gamma-interferon production), was significantly lower both before the treatment as after therapy, i.e. did not change during the whole study (28 weeks). In responders, a level of IL-1B production was higher than in controls before and during the treatment. In non-responders, it was similar to that in controls before the therapy, and increased during the treatment to a higher level.

Acute Disease↗
PubMedDate not supplied

Strategies for overcoming resistance in HIV-1 infected patients receiving HAART.

Highly active antiretroviral therapy (HAART) has fundamentally changed the clinical outcome of HIV infection and AIDS. However, the emergence of drug-resistant HIV variants is a barrier to successful use of HAART, with resistance to one drug often resulting in cross-resistance to many, if not all, others in the same class. The rise in the incidence of drug-resistant variants among newly infected patients also represents a formidable challenge for clinicians. Failure of the current HAART regimen due to drug resistance can severely limit second-line, third-line, and salvage treatment options. Although inadequate exposure of the virus to antiretroviral agents is a prime reason for the emergence of HIV drug-resistant variants, poor adherence to complicated regimens and variability in drug pharmacokinetics (PK), both within and between HIV-infected individuals, can also affect the overall efficacy of antiretroviral agents, promoting emergence of resistant HIV variants. Recent strategies to optimize antiretroviral drug regimens, including assessment of HIV genotype and/or phenotype, the use of protease inhibitor regimens that incorporate PK boosting, and scheduled treatment interruptions, have been explored. Additionally, several newer antiretroviral agents that produce rapid and sustained virologic and immunologic responses as well as novel resistance profiles (e.g. atazanavir and tenofovir) have become available. These characteristics thus increase the likelihood of durable viral suppression.

Adenine↗
PubMed2003

Correlation of clinical and laboratory surrogate markers of immunodepletion with T cell subsets (CD4 & CD8) determined flow cytometrically in HIV infected patients: a hospital based study.

CD4 count is established in HIV medicine as a marker of immune depletion. However, due to financial constraints this facility is not readily available in India. Therefore, this cross sectional study in the setting of a government hospital in Pune evaluated 72 HIV infected patients for the surrogate markers of CD4 count by correlating CD counts with clinical and easily available laboratory parameters. Using a data extraction Performa, the epidemiological and clinical data of these patients was noted. Routine hematological parameters were determined. T cell subsets were studied by 2-color flow cytometry. These included CD4 counts, CD4 percentage, CD8 counts, CD8 percentage and CD4/CD8 ratio. Status of cell-mediated immunity was determined using a Multi test CMI device and Mantoux reactivity. beta2 microglobulin levels were determined in 50 of the patients. Immunological parameters were correlated with the clinical profile and other simple laboratory markers. Statistical analysis was done using regression coefficients and paired t tests. Patients who had lesser weights had lower CD4 and CD8 counts, ALC (absolute lymphocyte counts) and CD4%. Fall in hemoglobin was associated with low CD4 count, low ALC and low CD8. ALC levels correlated well with CD4 counts below 500 cells / cmm. Patients with anergic skin response to Mantoux testing and impaired cell mediated immunity had lower CD4 counts than those who had intact cell mediated immunity. beta2 microglobulin levels did not correlate well with declining immune dysfunction. However a significant inverse correlation was established between beta2 microglobulin and CD4%.

AIDS-Related Opportunistic Infections↗
PubMedDate not supplied

Immune profile of women experiencing recurrent spontaneous abortions of unknown aetiology.

Immunological and immunogenetic investigations are described in a group of 28 women with a history of unexplained recurrent (greater than or equal to 3 consecutive) spontaneous abortions (RSA). Compared with female blood donor controls, recurrent aborters had significantly elevated mean serum complement C4 (p less than 0.05), but not C3, levels. Immunoglobulin levels and T4:T8 ratios showed a similar distribution to the controls. Mixed lymphocyte reactivities to partners' lymphocytes were low in some of the patients, but hyporesponsiveness correlated well with husband-wife HLA-DR compatibility. No individual HLA specificity was significantly increased in the RSA patients, but the combination A3, B7, DR2 was common (p less than 0.02), and general HLA antigen sharing with partners was significantly increased (p less than 0.004) relative to obstetrically normal couples. RSA women who shared two or more HLA antigens with spouses had higher mean serum immunoglobulin concentrations, which for IgM reached statistical significance (p less than 0.05).

Abortion, Habitual↗
PubMed1982

Parathyroid hormone immunoreactivity in the plasma filtrate of uremic patients.

Plasma filtrate of uremic patients concentrated and fractionated by gel filtration consisted of a large peak with C-terminal immunoreactivity and a small peak with N-terminal immunoreactivity. Further analysis of the first peak with C-terminal immunoreactivity by ion exchange chromatography revealed at least 3 peaks indicating the presence of three peaks with a similar immunological behavior but different charge. The elution profile in a patient under chronic hemofiltration was different in pattern compared with that in 2 patients under conventional hemodialysis.

Chromatography, Gel↗
PubMed1979

[Immunological studies and immunotherapeutic possibilities in inoperable bronchogenic carcinoma (author's transl)].

By establishing an immune profile combined with detailed clinical observation an attempt was made to assess the value of various therapeutic measures, especially immunological methods, in the treatment of inoperable bronchogenic carcinoma. The results indicated that in advanced cases specific immunological measures or stimulation of the immune mechanism only play a supportive role. Toxic side-effects or tumour enhancement were absent.

Aged↗