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Immunological profile of peripheral blood lymphocytes and monocytes/macrophages in Kawasaki disease.

Kawasaki disease (KD) is an acute illness of early childhood characterized by prolonged fever, diffuse mucosal inflammation, indurative oedema of the hands and feet, a polymorphous skin rash and nonsuppurative lymphadenopathy. The histopathological findings in KD comprise panvasculitis with endothelial necrosis, and the infiltration of mononuclear cells into small and medium-sized blood vessels. The levels of many proinflammatory cytokines, chemokines and adhesion molecules can be elevated in sera from children with KD at the acute stage. Although many immunological studies on KD involving peripheral blood have been reported, the data obtained remain controversial. This review focuses on the immune response of peripheral blood lymphocytes and monocytes/macrophages during acute KD.

Acute Disease↗

An immunologic profile of young adults with head and neck cancer.

Numerous reports have suggested, although never demonstrated, a suppressed immune defense mechanism as a contributing factor in the development of head and neck cancer in the young adult. Twenty-four previously untreated adults less than or equal to 40 years of age with squamous cell carcinoma were examined for lymphocyte function (natural killer cell activity and in vitro lymphocyte blastogenesis response to mitogens), total lymphocyte number and percentage of lymphocyte subsets, and humoral immune status (circulating IgA, IgG, and IgM). As compared with 33 healthy young adults, no significant immunologic deficit could be identified. On the contrary, the young adult cancer population had significantly increased lymphocyte numbers (P less than 0.05) and serum IgA, IgG, and IgM levels (P less than 0.001, respectively). These young cancer patients cannot be considered to be immunosuppressed. Alternative biologic mechanisms must be defined to account for the increasing incidence of head and neck cancer over the last decade among young adults in the United States.

Adult↗

[Immunologic profile in patients with acute anterior uveitis].

The authors investigated 52 patients (22 men and 30 women) with acute anterior uveitis where they ruled out systemic autoimmune disease, metabolic disease and focal or chronic infection. At the time of the infection the patients had not been treated for several months by any immunosuppressive treatment. The authors investigated in these patients serum concentrations of immunoglobulins G, A and M, the concentration of the C3 component of complement and the concentration of circulating immune complexes. Before the onset of therapy they investigated the response to antigens of the Immunoskin test. They assessed also the ratio of transplantation antigens class I by the microlymphocytotoxic test. They compared furthermore immunological indicators in subjects with a first attack and relapse of the disease and in groups, classified by the severity of the inflammatory symptoms. The authors detected significantly more frequently (p = 0.0005) the incidence of HLA-B27 antigen. Those where it was present were more frequently affected with a severe inflammation, as compared with subjects who did not have this phenotype (p less than 0.04). The relapse of the disease was more frequent in women (p = 0.1). The immunological laboratory findings did not differ in the first attacks and relapses of the disease, differences were, however, found in groups which differed as to the severity of inflammatory symptoms. In these groups the response rate to tests of skin sensitivity differed also. Based on these findings the authors assume that the ratio of immune processes in the development of acute idiopathic anterior uveitis cannot be ruled out.

Acute Disease↗

Immunological profiles in patients with acute retinal necrosis.

PURPOSE: Acute retinal necrosis (ARN) is a newly recognized disease caused by human commensal viruses of the herpes family (herpes simplex virus, varicella-zoster virus and cytomegalovirus) occurring in apparently immunocompetent patients. As at least three viruses can cause ARN, the modification in the host-virus interaction at the origin of the disease most probably comes from the host. A review of 216 reported cases of ARN showed that there were signs of impaired cellular immunity in 16% of these cases. The purpose of this study was to investigate immune parameters in ARN. METHODS: In nine HIV-negative ARN patients who were not under steroid or immunosuppressive therapy, the following prospective immunological investigations were performed: (1) skin testing for delayed-type hypersensitivity to seven common antigens (Candida, diphtheria, purified protein derivative tuberculin Proteus, Streptococcus, tetanus, Trichophyton); (2) lymphocytic proliferative responses in vitro to these antigens and to three mitogens; (3) determination of blood lymphocyte sub-populations by flow cytometry. RESULTS: Cutaneous anergy was found in five of seven tested cases. The lymphocyte proliferative index was less than 20% of the index of a control group for all antigens in three of nine cases, and for three or more antigens in eight of nine cases. In eight of nine cases there was a relative increase of B-lymphocytes, and in seven of nine cases B-lymphocytes were also increased in absolute numbers. In all nine cases one or more of these parameters were abnormal. CONCLUSION: Our findings suggest that ARN may develop in association with an imbalance of the immune system characterized by an impaired cellular response and/or a maintained or increased humoral response.

Adolescent↗

Immunologic profiles of effector cells and peripheral blood stem cells mobilized with different hematopoietic growth factors.

BACKGROUND: Peripheral blood stem cells (PBSC) have become the preferred source of stem cells for autologous transplantation because of the technical advantage and the shorter time to engraftment. Mobilization of CD34(+) cells into the peripheral blood can be achieved by the administration of G-CSF or GM-CSF, or both, alone or in combination with chemotherapy. G-CSF and GM-CSF differ somewhat in the number and composition of CD34(+) cells and effector cells mobilized to the peripheral blood. However, the molecular mechanism underlying the release and engraftment of CD34(+) cells is poorly understood. PURPOSE: The purpose of this review is to give a recent update on the type and immunological properties of effector cells and CD34(+) cells mobilized by the different growth factors with emphasis on A) mobilization of T cells, natural killer cells, and dendritic cells; B) coexpression of adhesion molecules such as VLA-4 and L-selectin in mobilized PBSC collection, and C) coexpression of CXCR4-the receptor for the stromal-derived differentiation factor 1-with latest information shedding light on the molecular mechanism underlying the release and subsequent engraftment of CD34(+) cells. CONCLUSIONS: A) The reported suppression of T cell and NK cell functions in PBSC apheresis collections in patients primed with G-CSF or GM-CSF is controversial and may merely reflect low effector cell activity before mobilization. B) A decrease in the expression of adhesion molecules such as VLA-4 and L-selectin is a necessary requirement for the release of CD34(+) cells to the peripheral blood. C) A decrease in the expression of CXCR4 is a necessary requirement for the release of CD34(+) cells to the peripheral blood and correlates with mobilization success.

Animals↗

Chemical and biological pollution contribute to the immunological profiles of free-ranging harbor seals.

Polychlorinated biphenyls and other persistent organic pollutants have been associated with immunotoxicity and outbreaks of (infectious) disease in marine mammals by rendering them vulnerable to infection by pathogens such as viruses and bacteria. In an immunotoxicological study of free-ranging harbor seals (Phoca vitulina), we obtained samples of blood and blubber from seal pups that were live-captured from two remote and two near-urban sites in British Columbia, Canada, and Washington state, USA. Using these samples, we quantified hematology, innate immune function, adaptive immune function, and polychlorinated biphenyl accumulation. While controlling for confounding factors (age, sex, and condition), univariate correlations between phagocytosis (r2 = 0.30, p = 0.002), respiratory burst (r2 =0.45, p= 0.000), T-lymphocyte function (r2 = 0.16, p = 0.028), lymphocyte signaling (r2 = 0.17, p = 0.025), and lymphocyte counts (r2 = 0.29, p = 0.002), and polychlorinated biphenyl concentrations suggested chemical-associated immunotoxicity. Principal component analysis of immunological endpoints provided additional evidence of immunotoxic effects in seals. However, principal component analysis also identified a noncontaminant-related factor by distinguishing between seals inhabiting urban versus remote sites, with results being consistent with increased pathogen exposure. Elevated fecal coliform concentrations in water, and observations of terrestrial spill-over pathogens in local seals, further support the notion of biological pollution at these sites. Although our study highlights the role that environmental contaminants might play in rendering marine mammal populations vulnerable to disease through immunotoxicity, it also suggests that biological pollution represents an emerging conservation concern.

Animals↗

Serum immunological profile in patients with chronic autoimmune cholestasis.

AIM: To compare patients who had biochemical and histological features of chronic autoimmune cholestasis (CAIC) using serological autoantibody profiling. METHODS: Patients (n = 174 CAIC; 79 AMA(-) and 95 AMA(+)) were profiled for the following antibodies: antinuclear antibodies (ANAs), antimitochondrial antibodies (AMAs), antismooth muscle actin (SMA, mainly F-actin), antiperinuclear cytoplasmic neutrophil antibodies (pANCAs), anti-SP100, anti-GP210, anti-M2 (2-oxo-acid dehydrogenase complexes), and antisoluble liver antigen (SLA). Liver specimens were reviewed according to staging, biliary interface activity, lobular hepatitis, granulomas, cholestasis, and florid ductal lesion. RESULTS: In patients who were AMA(-) by indirect immunofluorescence (IIF), 34.6% were positive for anti-M2 by immunoblotting. In 49 definitively AMA(-) patients, 24 (48.9%) showed ANA-primary biliary cirrhosis (PBC)-related antibodies (rim-like, multiple nuclear dots, anti-SP100, or anti-GP210). There were no differences in immunological, biochemical, or histopathological features between IIF-AMA(+) patients and AMA(-) patients with anti-M2 or ANA-PBC-related antibodies. AIH-related autoantibodies were found in 13 patients (7.5%). Patients with AMAs or ANA-PBC-related antibodies had higher IgM levels, whereas patients with antibodies highly specific for AIH had higher AST, bilirubin, and IgG levels, and AIH scores, and higher grades of lobular hepatitis. Overall, three distinct categories of patients were observed: AMA(+) or AMA(-) patients with ANA-PBC-related antibodies; AMA(-) patients with non-PBC-related ANAs; and patients with AIH-related antibodies together with serum PBC markers. CONCLUSION: Since these three groups had immunological, biochemical, and histopathological differences, they ought to be considered as separate clinical subentities rather than as merely AMA(-) or AMA(+) patients with autoimmune cholestasis.

Autoantibodies↗

Immunological profile in children with minimal change nephrotic syndrome.

Peripheral blood from patients with active stage of minimal change nephrotic syndrome (MCNS) was examined for concanavalin A (ConA)-inducible suppressor T cell activity, proliferative response to phytohemagglutinin (PHA) and in the autologous (AMLR) and allogeneic (MLR) mixed lymphocyte reaction, proportions of T cells with receptors for IgM (Tu) or IgG (T gamma) and the levels of serum immunoglobulin M, G and A. Six of 9 patients with MCNS studies showed deficiency of ConA-induced suppressor cell activity. In the AMLR, only one of 9 patients with MCNS demonstrated depressed proliferative response (p less than 0.05). In the allogeneic MLR, T cells from 5 of 9 patients with MCNS demonstrated poor proliferative response when stimulated with normal control non-T cells. Five of 9 patients with MCNS had depressed proliferative response to PHA. The proportion of total T cells, Tu cells and T gamma cells in the patient group were comparable to healthy control group. Serum IgG was significantly decreased in 7 of 11 patients. This study demonstrates multiple immunological abnormalities in patients with MCNS that might play a role in its pathogenesis.

Adolescent↗

Gingival status of HIV+ children and the correlation with caries incidence and immunologic profile.

PURPOSE: The aim of this study was to determine gingival health and caries levels in HIV-infected children. METHODS: The modified gingival index (GI) of 43 HIV+ children of both sexes, aged between 2 and 12 years, was measured and correlated with the DMFT/dmf. The children's immunodeficiency level was also established by means of the CD4:CD8 ratio. Pearson's product-moment correlation co-efficient and the Mann-Whitney U test were used. RESULTS: The GI was significantly related to the DMFT/dmf. The children with a GI = 0 presented significantly more DMFT/dmf than the children with a GI > or = 0.1, but there were no significant differences between the GIs of caries-free children and those with DMFT/dmf > or = 1. The children who presented a CD4:CD8 > or = 0.5 ratio presented less DMFT/dmf compared with children who presented a CD4:CD8 < 0.5 ratio. The children who presented a CD4:CD8 < 0.5 ratio presented a statistically significant correlation between their GI and their DMFT/dmf, unlike children who presented a CD4:CD8 > or = 0.5 ratio. Children with a CD4:CD8 < 0.5 who showed a greater DMFT/dmf index also showed greater gingival inflammation. CONCLUSIONS: In this study, children with greater caries experience showed more gingival inflammation. In addition, a greater immunological deficiency might indicate a greater caries experience in children.

CD4 Lymphocyte Count↗

Self-adjusted postmenopausal hormone replacement therapy: effects on the biological and immunological profile of FSH and correlation to climacteric symptoms.

OBJECTIVE: The purpose of the present study was to evaluate the hormonal profile of patients of postmenopausal age during estrogen replacement therapy (ERT) with special reference to the serum levels of biologically active FSH (B-FSH) in a self-adjusted ERT model. DESIGN: The hormonal values found have been correlated to climateric symptoms reported by the patients (scored by the Kupperman menopausal index (KI)). METHODS: B-FSH was measured using an assay based on a cell system transfected permanently with FSH receptor cDNA. All women (n=32) applied estradiol percutaneously using 1 mg estradiol-17beta (E(2)) as an initial dose and were encouraged to increase the daily dose until they felt comfortable according to a specific scheme. Twelve of the 32 women were hysterectomized and treated, accordingly, with ERT only; 20 women received megestrol acetate monthly for 10 days. RESULTS: The initial average KI was 30 (range 10-54). A high degree of correlation (r=0.83; P<0.001) was observed between B-FSH and immunologically active FSH (I-FSH). Serum I-FSH and E(2) correlated negatively (r=-0.21; P<0.001); similarly, a negative correlation (r=-0.15; P<0.01) was observed between serum B-FSH and E(2) levels. Serum I-FSH and KI showed modest but significant positive correlation (r=0.13; P<0.01); a somewhat higher degree of correlation (r=0.19; P<0.005) was observed when B-FSH and KI were compared. E(2) showed positive correlation to serum sex-hormone binding globulin levels (r=0.22; P<0.001). CONCLUSIONS: This study shows that the transdermal self-adjusted hormone replacement therapy (HRT) model introduced is suitable for studies on endocrine changes during postmenopausal ERT. The finding of poor correlation between serum E(2) levels and KI emphasizes the importance of hormonal measurements during postmenopausal HRT.

Climacteric↗

Immunological profiles of leprosy patients and healthy family contacts toward M. leprae antigens.

In this study, we measured simultaneously the in vitro and in vivo T lymphocyte reactivities and the antibody responses of leprosy patients and healthy family contacts (HFC) toward Mycobacterium leprae antigens. The in vitro lymphoproliferative response of the HFC to leprosin A was comparable to that of tuberculoid leprosy patients. However, their skin-test reactivity to Dharmendra lepromin was considerably higher compared to the in vitro response to leprosin A. A significant number of HFC failed to respond to M. leprae antigens, both in vitro and in vivo, and the unresponsiveness to either test was not related to the type of leprosy patients in the household. A marginal correlation was observed between the skin-test reactivity of HFC and the age of the individuals. Even though a significant proportion of HFC showed positive anti-PGL-I IgM levels, none showed a positive titer in the serum antibody competition test toward the M. leprae-specific epitope My2. A positive anti-PGL-I IgM response together with a negative lepromin skin-test reactivity showed a clear downward trend from the lepromatous pole toward the tuberculoid pole. A small number of HFC, all contacts of lepromatous patients, were lepromin skin-test negative with positive anti-PGL-I IgM levels, but the majority among them showed T-cell reactivity to mycobacterial antigens in vitro. These results are discussed in relation to immunological correlates of the susceptibility to M. leprae infection.

Antibodies, Bacterial↗

Multiple myeloma: an immunologic profile. Cytotoxic and suppressive effects of the EA rosette-forming cell.

Lymphoid cells bearing receptors for human IgG anti-Rh antibody but not otherwise identifiable as T or B cells were isolated from the peripheral blood of human multiple myeloma patients. These cells do not demonstrate surface immunoglobulin, do not secrete immunoglobulin in culture after stimulation with pokeweed mitogen, and do not possess receptors for the third component of complement. They do not form rosettes with sheep erythrocytes, and do not respond to known T cell mitogens. These cells are not phagocytic and do not possess demonstrable nonspecific esterase. Thus, they must be considered at present, members of the "third population" lymphoid cells. These cells are active in the cytotoxic response by myeloma peripheral blood lymphocytes to myeloma plasma cells accounting for approximately 60% of such activity. They are also responsible for part of the suppression of pokeweed mitogen-stimulated immunoglobulin production, and at equivalent suppressor to target cell ratios are more active than immunoregulatory monocytes. Thus, these cells play an important, not previously widely appreciated role in the pathophysiology of the human myeloma patient.

Antibodies↗

The immunological profile of a new immunomodulatory agent, oxamisole.

Oxamisole is a T-cell immunorestorative agent when administered by the oral (p.o.) route. It has little or no effect on the IgM or IgG responses to the T-dependent antigen, sheep erythrocytes (SRBC), in normal mice but augments antibody production in immunodeficient animals. Unlike the response to SRBC, the humoral immunocompetence of both normal and immunosuppressed animals sensitized with the T-independent antigen, trinitrophenyl-lipopolysaccharide (TNP-LPS) was unaffected by oxamisole. Oxamisole restored cellular immunocompetence, as evidenced by an increase in the in vitro proliferative response of normal murine splenocytes to T-cell mitogens, while decreasing B-cell mitogenic responses. This indicates that oxamisole may selectively restore T-cell function. However, oxamisole did not significantly modify the classical T-cell-mediated delayed hypersensitivity responses to either the protein antigen methylated bovine serum albumin or to the contact-sensitizing antigen oxazolone. When assayed in vitro, oxamisole enhanced macrophage chemotactic function but not phagocytic function, suggesting a potential stimulation of the reticuloendothelial system. In vivo studies failed to demonstrate any consistent significant activation of murine macrophage function following oral dosing with oxamisole.

Adjuvants, Immunologic↗

Long-term spontaneous regression of malignant melanoma with visceral metastases. Report of a case with immunologic profile.

A case of a 58-year-old woman with viscerally metastatic malignant melanoma is presented 12 years after spontaneous and complete regression of disease. Diagnosis of primary and metastatic lesions was confirmed by review of tissue sections. The presence and subsequent absence of visceral metastases were documented by open liver biopsies. Sections of metastatic lesions revealed extensive necrosis of tumor and infiltration of lymphocytes and plasma cells. Skin testing showed a strongly positive delayed hypersensitivity response to dinitrochlorobenzene (DNCB), to a standard battery of bacterial and fungal antigens, and to two of four preparations of allogeneic melanoma antigens. Values for cell- and serum-mediated cytotoxicity against melanoma cells and the response of the patient's lymphocytes to phytohemagglutinin were slightly above the normal range. A review of the literature reveals 13 other cases of long-term spontaneous regression of melanoma. None of these, however, had biopsy evidence of visceral disease. In each of the 13 cases, regression was associated with an event that might be inferred to have altered the patient's hormonal or immune status. This patient also provides evidence of a complete, spontaneous, and long-term remission of metastatic disease associated with the spontaneous development of host immunity.

Autoantigens↗

Immunological profile after splenectomy in children with beta-thalassaemia major.

The in vitro immune functions of peripheral blood lymphocytes have been studied in 12 children with beta-thalassaemia major and hypersplenism. The study was performed prior to splenectomy and on the 2nd, 6th, 15th and 30th day after splenectomy. It was found that before splenectomy, patients had low numbers of blood leucocytes, normal rosette and T3 lymphocyte counts, low T4 and normal T8 lymphocyte counts with a T4/T8 ratio below 2, impaired T lymphocyte mitogenic responses induced by PHA, increased numbers of polyvalent and monovalent B lymphocytes and normal immunoglobulin levels of IgG and IgA. After splenectomy, especially on the 2nd day, leucocytosis, a significant decrease of T cells and their subsets and a reduction of the IgM levels were found. These parameters, except the IgM levels, increased until the 30th day after splenectomy and reached presplenectomy values. On the 2nd day after splenectomy, large mononuclear cells behaving like immunocytes appeared in the peripheral blood. They had the phenotype of T3, T4, T8, B lymphocytes and OKM1 monocytes. All the large mononuclear cells increased significantly on the 6th day after splenectomy and remained elevated during the whole study (30 days). The T4/T8 ratio was increased, but no increase was found in the functional responses of T lymphocytes.

Adolescent↗

A comparison of immunologic profiles and their influence on bacteremia in surgical patients with a high risk of infection.

Prospective sequential studies of the antibacterial function of neutrophils, lymphocyte responsiveness, opsonic capacity of serum and serum levels of C3(B), properdin, factor B, IgG, and albumin were made in 32 patients with severe burn injury (greater than or equal to 45%), 21 patients with severe multisystem traumatic injury, 20 high-risk, infected patients, and 22 renal transplant patients. Fifty-five episodes of bacteremia occurred in 37 of the 95 patients. Abnormal neutrophil function was clearly associated as a predisposing factor to these episodes, whereas there was no association between bacteremia and low serum levels of C3, IgG, factor B, or properdin. C3, factor B, and IgG usually rose following bacteremia as acute phase proteins, but there was evidence of a consumptive opsoninopathy in 11% of episodes. Defective opsonization was associated with a high risk of bacteremia only when there was a coexisting abnormality of neutrophil function (88% of such patients became bacteremic). None of 27 nonburned patients tested with delayed hypersensitivity antigens responded normally, and there was regularly depression of lymphocyte responsiveness to phytohemagglutinin-A and concanavalin-A in a whole blood assay related to serum immunosuppressive factors, but poor responsiveness was not associated with bacteremia.

Adolescent↗

Multiple myeloma: an immunologic profile. I. Peripheral blood studies.

Seventy-four patients with multiple myeloma, 17 untreated and 57 treated, were studied to characterize their peripheral blood lymphocytes. PBL were studied for E, EAC, and EA rosette-forming cells, SIg, and Fc receptor-bearing cells. The responses to HA, Con A, and PWM were assessed as well as their ability to stimulate or to respond in a MLC. Finally, the capacity of mitogen-stimulated lymphocytes to lyse Chang cells, CRBC, and PHA-stimulated lymphoblasts was examined. These results were compared with a group of normals and patients with benign monoclonal gammopathy. In untreated myeloma patients there was a normal percentage of T cells, but an abnormal distribution of B cells as judged by a decrease in SIg-bearing cells, as well as an increase in EAC rosette-forming cells. Subpopulation analysis showed a marked increase in EAC rosette-forming cells without SIg. PHA, Con A, and PWM, and response in MLC were all normal. However, the ability to stimulate in MLC was significantly depressed. Treated myeloma patients had similar findings, except that the response to PWM was significantly depressed. The capacity of PWM-stimulated cells to lyse target cells was depressed in both groups. The results indicate that, in the peripheral blood of myeloma patients, there are populations of lymphocytes characterized by the presence of the EAC receptor without SIg, which are deficient in the capacity to stimulate an MLC response and the ability to be cytotoxic when stimulated by PWM. The results form a baseline for the study of abnormal lymphoid function in human myeloma.

Adult↗

Immunological profile of patients awaiting a renal transplant.

BACKGROUND: A renal transplant is the best possible treatment for patients with terminal renal failure. Advances in the development of techniques of screening of pre-formed antibodies have contributed to a notable improvement in the results obtained with allogenic transplants. METHODS: The aim of the present work is to study the nature, class, isotype and specificity of antibodies detected in patients awaiting renal transplantation at Complejo Hospitalario Universitario Juan Canalejo, as well as their relation with the level of anti-human leucocyte antigen (HLA) sensitization. RESULTS: In all patient groups, there was a predominance of IgG. The distribution of anti-HLA antibody class showed that the most frequent pattern corresponded to a mixture of class I and class II antibodies for all groups. The study of specificity of anti-HLA antibody showed that of the patients with at least one previous transplant, 72% developed specific anti-HLA antibodies against some of the incompatible antigens of the donor, 12% against HLA antigens not related with the phenotype of the donor and in 16% it was not possible to determine their specificity. Most patients developed antibodies against antigens of locus B, probably because of that the number of incompatibilities contributed by the donors is also greater for locus B. CONCLUSIONS: The exhaustive study of sera of patients on a waiting list for transplantation with respect to the nature, isotype, class and specificity of the antibody is important since it is possible that different antibodies can bring about, in the transplant, events that will have different consequences for the survival of the graft.

Adult↗