Conference on advances in AIDS vaccine development--1993. Summary: correlates of HIV Immunity Working Group.
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AIDS Vaccines↗
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Results for “Immune correlation”
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[Correlation of specific immune response and tuberculous changes in the lungs].
A clinicoimmunological examination of 312 new-onset cases of tuberculosis was performed to investigate the relationships between factors of humoral and cellular immunity and tuberculous process. Specific immune response (SIR) and the trends in the disease progress showed some interdependences. The forms of SIR reported can serve criteria for alterations in the lungs and prognosis of the process outcome.
Adolescent↗
Clinical benefits and immunopathological correlates of intravenous immune globulin in the treatment of inflammatory myopathies.
High-dose intravenous immune globulin (IVIG) is emerging as a promising therapy for patients with inflammatory myopathies who have become unresponsive to, or cannot tolerate, conventional therapies. In a double-blind, placebo-controlled study, using objective criteria for improvement, IVIG demonstrated moderate to dramatic improvement in 75% of the patients with dermatomyositis. Preliminary results from a controlled study in inclusion-body myositis show that IVIG may also exert a mild benefit, but only in a small number of patients and in certain muscle groups. In some patients with polymyositis, IVIG is reported to be of benefit but controlled studies have not yet been completed. Immunocytochemical, immunological and in vitro studies on the patients' repeated muscle biopsies and follow-up sera showed that IVIG exerts its action in inflammatory myopathies by: (i) inhibiting myotoxic cytokines, such as TNF-alpha and IL-1; (ii) blockade of Fc receptors on endomysial macrophages interfering with Fc receptor-mediated phagocytosis; and (iii) inhibiting the uptake of C3 and intercepting the formation and deposition of membranolytic attack complex on the endomysial capillaries.
Humans↗
Immune complexes: characteristics, clinical correlations, and interpretive approaches in the clinical laboratory.
Immune-complex-mediated injury is thought to play a role in diseases such as rheumatoid arthritis, systemic lupus erythematosus, serum sickness, various infectious diseases, and malignancies. With increased appreciation of the biological and pathological significance of circulating immune complexes has come efforts to develop appropriate techniques for identifying and measuring them. Common approaches exploit such phenomena as the attachment of complement components to antigen-antibody complexes, the presence of specialized receptors for immune complexes at the surface of cells, and the ability of rheumatoid factor to bind with immune complexes. This variety of assay systems for immune complexes has yielded abstruse results in numerous human pathological conditions. Unfortunately, these results seldom correlate with one another in a given disease. Thus, use of a panel of immune complex assays has been recommended. Indirect consequences of immune complex disease may still be appraised and evaluated with some confidence in clinical medicine: measurements of C3 and C4, cryoglobulins, serum viscosity, and turbidity of serum samples. Measurement of immune complexes may be useful in diagnosis, prognosis, and therapeutic monitoring, but it is the characterization of immune complexes that holds the greatest potential for better understanding of disease mechanisms.
Antigen-Antibody Complex↗
The effect of antibody isotype on the activation of C3 and C4 by immune complexes formed in the presence of serum: correlation with the prevention of immune precipitation.
Radioimmunoassays for C3a and C4a have been used to measure the activation of complement during the formation of immune complexes in human serum by the interaction of DNP-BSA and each of 11 mouse anti-DNP monoclonal antibodies of varied isotype and affinity. Those containing IgG2 or IgM were potent activators of C4, whilst IgG1 containing complexes were less efficient. C3 activation in normal serum was similar for complexes containing IgG1, IgG2a, IgG2b or IgM. IgA complexes did not activate C3 or C4. All complexes except those containing IgA precipitated more slowly in serum than in buffer. IgG2 antibodies were potent activators despite being very slow to precipitate in buffer. In serum containing EGTA activation of C4 was abolished and precipitation of complexes occurred at the same rate as in buffer. Nevertheless, C3 activation still occurred by the alternative pathway for all IgG and IgM complexes. Antibodies of the same isotype did not necessarily activate complement to the same extent. The ranking of the ability to activate complement was the same as that observed when performed complexes containing the same antibodies were added to serum. The levels of C4a generated were similar under both conditions but for most antibodies more C3a was generated by preformed complexes.
Antibodies, Monoclonal↗
Immunity in Graves' disease at diagnosis: correlation between activated T cells and humoral immune factors.
Activated T cells, T-cell subsets, thyrotropin receptor antibodies and immune complexes were evaluated in 31 patients with newly diagnosed Graves' disease. Activated T cells were assayed by monoclonal antibodies against early (4F2) and late activation surface lymphocyte antigens (different epitopes of class II antigens). In comparison with the normal population, Graves' patients showed a significant decrease in the suppressor cytotoxic T-cell subset. Significant increases of 4F2-positive cells (70% of patients studied), class II antigen-positive cells (65%), thyrotropin receptor antibodies (93%), Clq-immune complexeses (44%) and conglutinin-immune complexes (37%) were observed. A significant inverse correlation between the increase in 4F2-positive cells and thyrotropin receptor antibody values was also observed. Lymphocytes from Graves' patients were cultured in the presence of thyrotropin receptor antibody-positive or -negative sera, with or without mitogen stimulation. Thyrotropin receptor antibodies were shown not to interfere with the expression of activation antigens in cultured cells. The different patterns of humoral and cellular immune phenomena may indicate the existence of either different stages of Graves' disease or a heterogeneity of the immunopathogenesis in different patients.
Adolescent↗
Tumor size and lymph-node status in pancreatic carcinoma - is there a correlation to the preoperative immune function?
BACKGROUND AND AIMS: It has not been clarified whether there is a correlation between the tumor size and the preoperative immune function in pancreatic carcinoma. PATIENTS/METHODS: In a prospective trial, the influence of tumor size and lymph-node status on different immune system factors [interleukins (IL)-6 and -10, tumor necrosis factor (TNF)-alpha, CD3-, CD4-, and CD8-lymphocytes, and human leukocyte antigen (HLA)-DR-monocytes] was analyzed in 28 patients with pancreatic carcinoma and compared with a control group (n=20). There were 3 pancreatic carcinomas of the T1-tumor type, 20 T2- and 5 T3-tumors; 14 patients were in stage N1. RESULTS: In comparison with the control group, tumor patients preoperatively showed a significant increase of leukocytes (P=0.02), monocytes (P=0. 04), and granulocytes (P=0.03). The total count of lymphocytes, the number of CD3-, CD4- and CD8-lymphocytes, and the expression of HLA-DR on monocytes were significantly decreased as a sign of immunosuppression in tumor patients. A multivariate analysis proved that only tumor size (T-stage) but not lymph-node status correlates with the deficiency of immune competence. Progressive tumor size correlated with decreasing expression of HLA-DR on monocytes, CD3- (P=0.04) and CD8- (P=0.02) lymphocytes. In contrast IL-6, IL-10 (P=0. 04) and TNF-alpha (P=0.02) increased with progressive tumor size. CONCLUSION: Regarding the negative prognosis after resection, the preoperative immune status could be an additional help for decision between a resection or a preoperative immune stimulation in pancreatic carcinoma.
Case-Control Studies↗
Treatment of recurrent spontaneous abortion by immunization with paternal lymphocytes: correlates with outcome.
Previous observations have suggested that defective recognition of fetal alloantigens by the maternal immune system is associated with recurrent pregnancy failure and that this may be prevented by boosting the maternal immune system with paternal or pooled third-party leukocytes. The mechanism whereby this process achieves success is not clear, and accordingly to explore this we immunized 28 couples with recurrent fetal loss with 80 x 10(6) paternal peripheral blood mononuclear leukocytes (PBML) and followed various immunological parameters. The couples studied, in whom 55% achieved a successful pregnancy, showed no increase in sharing of human lymphocyte antigen (HLA)-A, -B, or -DR antigens and no consistent evidence of a decreased mixed leukocyte reaction (MLR) or MLR plasma-blocking factors compared with control couples. Immunization did not alter these parameters but did induce antipaternal lymphocytotoxins, although the presence of the latter did not correlate with pregnancy outcome. There was a correlation between rapid conception after immunization and a subsequent successful pregnancy. A successful pregnancy also correlated with sustained postimmunization, postconception maternal antipaternal allospecific CD-8+ suppressor T cells. Although these findings provide overall evidence that immunization produces changes in the way in which the maternal immune system interacts with the fetus, larger numbers of couples and a higher dose of paternal lymphocytes will be needed to establish clearly whether this therapy works and its mechanism of action.
Abortion, Spontaneous↗
Bridging studies.
The duplication of usually large-scale efficacy trials to generalise the clinical database of a new vaccine to other populations can be avoided by bridging studies. Immunogenicity data can easily be used to extrapolate efficacy results when the immune response correlates with vaccine induced immunity. In the absence of such a correlate of protection, the bridging process will be more controversial. Previous experiences should be valuable in identifying the factors, either ethnic or vaccine-related that may have an influence on vaccine efficacy. The probability that such a factor is associated with a clinically significant difference in efficacy is critical to the decision to conduct a bridging study. Bridging studies are designed to demonstrate equivalent immunogenicity i.e. exclude a clinically significant difference in the immune response between the population in whom efficacy was shown and the population to whom those efficacy results are extrapolated.
Clinical Trials as Topic↗
51Chromium-release microassay technique for cell-mediated immunity to mumps virus: correlation with humoral and delayed-type skin hypersensitivity responses.
Lymphocyte-mediated immune responsiveness to mumps virus was studied with use of a 51chromium (51Cr)-release microassay of lymphocytotoxicity to target cells persistently infected with mumps virus. The release of 51Cr from immune cells was found to be virus-specific and reproducible and correlated well with the presence of antibody but not with the magnitude of antibody levels. Delayed-type skin hypersensitivity and specific immune release of 51Cr did not correlate well, which suggests that the two events may be mediated by different populations of cells.
Antibody Formation↗
Prognostic evaluation of cell mediated immunity in leprosy and correlation with clinicopathological status of leprosy patients.
Cell mediated immunity was studied in 50 patients of leprosy and 15 control volunteers, by estimation of peripheral blood lymphocytes (PBL), total rosette forming cells (TRFC) and active rosette forming cell (ARFC) counts in vitro. PBL, TRFC and ARFC counts were slightly but not significantly increased in patients of tuberculoid leprosy (TT) and muculoanaesthetic variant of tuberculoid leprosy as compared to control group. However, gradual decrease in T-cell subsets, occurred in borderline tuberculoid leprosy (BT) as compared to tuberculoid type (TT)-(p < 0.05). Significant decrease in lymphocytes and T-cell subsets was observed in midborderline leprosy (BB), (p < 0.01):borderline lepromatous leprosy (BL), (p < 0.001) and lepromatous subpolar and polar types (LL); (p < 0.001) as compared to control group. Mycobacterium leprae (M.leprae) were positive in BT-(20%); BB-(72.7%); BL-(83.2%) and LL-(100%). Delayed hypersensitivity reactions (DHR) revealed significantly increased lepromin positivity in TT (83.3%) and BT (80%) which decreased in BB (63.6%) and BL (50%). Lepromin test showed anergic state in LL group (28.5% positivity). Dinitrochlorobenzene (DNCB) skin test showed 100% positivity in TT group and controls while gradual significant decrease was observed from BT (p < 0.05) to LL scale (p < 0.001). Leprosy spectrum of Ridley and Jopling scale is directly co-related with inherent cell mediated immune status of the patients which has a significant prognostic role in treatment and long term management.
Adolescent↗
Plasma exchange in immune complex glomerulonephritis: clinical and immunological correlations.
22 patients with immune complex (IC) glomerulonephritis (GN) were treated with plasma exchange (PE), corticosteroids and immunosuppressors, in 4 cases also as a long treatment. We evaluated circulating IC and some neutrophils (PMN) functions such as phagocytosis, aggregation and platelet activating factor (PAF) release. In extracapillary GN improvement was observed in 3/9 patients, concomitantly with IC decrease: in 6/9 patients no renal amelioration occurred, despite IC decrease in two. In all Lupus Nephritis and mixed IgG/IgM cryoglobulinemia, IC were highly positive and the disappearance of IC in 5/6 Lupus Nephritis and 4/4 cryoglobulinemia heralded systemic and renal amelioration. PMN functions were hampered in acute Lupus Nephritis and mixed cryoglobulinemia, but constantly improved along with IC decrease and clinical amelioration. Thus in extracapillary GN the decrease of IC by PE may not eventuate in renal improvement. In Lupus Nephritis and cryoglobulinemia a better correlation exits between IC, PMN function and clinical course.
Cryoglobulinemia↗
Persistence of intracellular HIV-1 mRNA correlates with HIV-1-specific immune responses in infected subjects on stable HAART.
OBJECTIVE: To determine if low level, persistent, HIV-1 replication within specific immune cells contributes to HIV-1-specific immune responsiveness. DESIGN: We analyzed 59 HIV-1-infected subjects on stable highly active antiretroviral therapy (HAART) therapy (not including zidovudine) with suppressed plasma viremia (< 400 copies/ml) for phenotypic and lymphoproliferative correlates of immune function. METHODS: Peripheral blood mononuclear cells were collected for immunophenotyping, lymphoproliferative assays, and simultaneous immunophenotyping/ultrasensitive in situ hybridization. Plasma was collected for plasma viral load as determined by the Ultra Sensitive Roche Amplicor RT-PCR. Descriptive statistics (mean and SD, median, first and third quartiles) were determined for all variables in two groups defined as having persistent viral replication present or absent. The two-sided Wilcoxon test (continuity correction, 0.5) was used to compare lymphocyte phenotypes, lymphoproliferative assay responses, intracellular gag-pol mRNA, lowest CD4 counts and CD4% of these two groups. RESULTS: HIV-1 replication in CD4, CD45RO memory T lymphocytes persists in spite of undetectable plasma viral load. Patients (n = 24) with persistent intracellular expression of HIV-1 mRNA (> 0.3%) showed significant in vitro proliferative responses to HIV-1 p24 (stimulation index > or = 10) compared to patients (n = 35) without persistent intracellular replication. The group with persistent HIV-1 replication in cells showed no significant response to the recall antigen tetanus toxoid but a trend toward higher responses to pathogen antigens. There were no differences between the groups in the prevalence of AIDS or occurrences of opportunistic infections; however, the high viral persistence group was more HAART experienced (P < 0.05). CONCLUSIONS: These results suggest that HIV-1-specific immune responses correlate with evidence of ongoing HIV-1 replication.
Antiretroviral Therapy, Highly Active↗
Resistance to HIV infection.
The biological correlates of an effective immune response that could contain or prevent HIV infection remain elusive despite substantial scientific accomplishments in understanding the interactions among the virus, the individual and the community. The observation that some individuals appear to possess resistance to HIV infection or its consequences has generated a host of epidemiologic investigations to identify biological or behavioral characteristics of these individuals. These data might hold the keys to developing appropriate strategies for mimicking the effective responses of those who appear immune. In this paper we review genetic mechanisms including the role of chemokines and their receptors, cytokines, host genetic immune response to HIV infection, local immune response correlating with behavioral variables, co-infection and immune based mechanisms that have been elucidated so far. We offer suggestions for how to use these observations as platforms for future research to further understand natural resistance to HIV infection through cohort studies, population genotype sampling, mathematical modeling of virus-host interactions and behavioral analyses.
Chemokines↗
Immune complexes associated with brain tumors: correlation with prognosis.
The presence of circulating immune complexes in the sera of 208 patients with intracranial space occupying lesions was assayed using the C1 q binding test. Twenty-eight percent of 96 high grade glioma patients had immune complexes as compared to 14% of 28 low grade glioma patients. The incidence of immune complexes was found to decrease in the first post-operative month. The presence of immune complexes correlated with shorter survival in a group of malignant glioma patients tested preoperatively. Nineteen patients without immune complexes had a mean survival of 8.6 months as compared to 13 patients with immune complexes who had a mean survival of 4.7 months. These results confirm similar observations in other types of malignancies.
Adult↗
Induction of mucosal immune responses and protection against enteric viruses: rotavirus infection of gnotobiotic pigs as a model.
Enteric viruses are a major cause of diarrhea in animals and humans. Among them, rotaviruses are one of the most important causes of diarrhea in young animals and human infants. A lack of understanding of mechanisms to induce intestinal immunity and the correlates of protective immunity in neonates has impaired development of safe and effective vaccines against enteric viruses. Studies of candidate vaccines using an adult mouse model of subclinical enteric viral infections often do not predict vaccine efficacy against disease evaluated in neonatal large animals. A series of studies have been conducted using a neonatal gnotobiotic pig model of rotavirus infection and diarrhea to identify correlates of protective immunity and to evaluate traditional and novel vaccine approaches for the induction of mucosal immune responses and protection to enteric viruses. Gnotobiotic pigs recovered from infection with virulent Wa human rotavirus (HRV) (mimic natural infection) had high numbers of intestinal IgA rotavirus-specific primary antibody-secreting cells (ASCs) and memory B-cells (to recall antigen) measured by ELISPOT assay, which correlated with complete protection against rotavirus challenge. Most short-term IgA memory B-cells were resident in the ileum, the major site of rotavirus replication. Spleen, not the bone marrow, was the major resident site for longer-term IgG memory B-cells. Candidate rotavirus vaccines evaluated in pigs for their ability to induce intestinal or systemic ASC and protection against rotavirus infection and diarrhea included attenuated live virus, inactivated virus, and baculovirus-expressed double-layered rotavirus-like particles (2/6-VLPs). In combination with those candidate vaccines, various adjuvants, delivery systems, and immunization routes were tested, including incomplete Freund's adjuvant for i.m. immunization, and a mutant Escherichia coli heat labile enterotoxin R192G (mLT) for i.n. immunization. It was shown that orally administered replicating vaccines were most effective for priming for intestinal IgA ASC and memory B-cell responses, but i.n. administered non-replicating 2/6-VLPs plus mLT were effective as booster vaccines. We conclude that protective immunity depends on the magnitude, location, viral protein-specificity, and isotype of the antibody responses induced by vaccination. Therefore highly effective enteric viral vaccines should: (i) induce sufficient levels of intestinal IgA antibodies; (ii) include viral antigens that induce neutralizing antibodies; and (iii) require the use of effective mucosal adjuvants or antigen delivery systems for non-replicating oral or i.n. vaccines.
Animals↗
CD1 expression by dendritic cells in human leprosy lesions: correlation with effective host immunity.
A potential role for the CD1 family of lipid Ag-presenting molecules in antimicrobial immunity in vivo was investigated in human leprosy skin lesions. Strong induction of three CD1 proteins (CD1a, -b, and -c) was observed in dermal granulomas in biopsy samples of involved skin from patients with the tuberculoid form of leprosy or with reversal reactions, which represent clinical patterns of disease associated with active cellular immunity to Mycobacterium leprae. In contrast, lesions from patients with the lepromatous form of the disease who lack effective cell-mediated immunity to the pathogen did not show induction of CD1 proteins. Thus, expression of CD1 correlated directly with effective immunity to M. leprae, as assessed by the clinical course of infection. CD1a, -b, and -c could be induced to similar levels on monocytes from the blood of either tuberculoid or lepromatous leprosy patients. This suggested that the absence of expression in lepromatous lesions was most likely due to local factors at the site of infection as opposed to a primary defect of the CD1 system itself. The majority of cells expressing CD1 in leprosy lesions were identified as a population of CD83+ dendritic cells. Initial in vitro studies of the Ag-presenting function of CD1+CD83+ monocyte-derived dendritic cells showed that such cells were highly efficient APCs for CD1-restricted T cells. These results indicate that the CD1 system can be up-regulated in human infectious diseases in vivo, and may play a role in augmenting host defense against microbial pathogens.
Antibodies, Monoclonal↗
Major histocompatibility complex class II antigen expression during potentiation of line-10 tumor immunity after intralesional administration of bacillus Calmette-Guérin.
Intralesional injection of BCG into an established line-10 hepatocellular carcinoma in the strain-2 guinea pig causes regression of the tumor and induction of line-10 immunity. We found that the animals were already protected for a second challenge with line-10 tumor cells 7 days after BCG treatment. We studied whether this early induction of immunity was correlated with the expression of MHC class II antigens on line-10 tumor cells and was correlated with an increased expression of MHC class II antigens on leukocytes in the primary tumor and in the regional lymph node (Ln. axillaris accessorius). The MHC class II antigens and the leukocyte subpopulations were measured with monoclonal antibodies and flow cytofluorometry. In the draining lymph node the number of nucleated cells increased about 10-fold during the first 5 days after intralesional injection of BCG. At this time the MHC class II antigen expression of these cells was increased from 21%-32% in the naive controls to 39%-53% in animals with BCG-treated tumors. This implies that the number of MHC-class-II-positive cells increased about 20-fold in the draining lymph node. Surprisingly, the increase in percentage of MHC-class-II-antigen-positive cells was mainly due to an increase of IgM-positive B cells from 8%-11% to 22%-41% and an increase of IgG-positive B cells from 7%-27% to 25%-44%. In the tumor, BCG treatment induced a small increase of MHC-class-II-antigen-positive cells from 11%-12% to 15%-20%. Probably this increase came not from tumor cells but mainly from a BCG-induced infiltration of mononuclear cells, as an increase of T cells from 14% to 20%, an increase of macrophages from 8% to 18%, and an increase of B cells from 0 to 6% was observed. We conclude that the potentiation of anti-(line-10 tumor cell) immunity correlated with a 20-fold increase of MHC-class-II-antigen-positive cells in the lymph nodes and a small increase in the number of MHC-class-II-antigen-positive tumor-infiltrating cells.
Animals↗