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Hepatitis B virus-associated membraneous nephropathy: clinical features, immunological profiles and outcome.

To evaluate the clinical features, immunological profiles and the prognosis of hepatitis B virus-associated membraneous nephropathy (HBVMN), 34 patients (25 boys and 9 girls) were studied from April 1981 to November 1987. With Fab fragments of monoclonal antibodies, hepatitis B e antigen (HBeAg) was detected in the glomerular deposits from 30 cases (88.2%) and in the sera from 32 cases (94.1%). These results suggest that HBeAg plays an important role in the development of HBVMN. In addition, clinical trials of 32 cases demonstrate a relatively poor response to the steroid therapy with persistent heavy proteinuria (32.4%) or a high frequent relapse rate (38.2%); only 1 case (3.1%) had early response. In 4 cases follow-up renal biopsy was performed, progressive sclerosis with interstitial fibrosis being noted in each instance. The stage of membraneous nephropathy examined under the light microscope, had progressed from stage I or II to stage III. One had impaired renal function. Therefore, HBVMN does not always take a benign course. In the immunological profiles, significant hypocomplementemia with low C3, C4 and properdin factor B levels were found during the initial 6 months after the onset of disease. Hepatitis B surface antigen (HBsAg) circulating immune complexes (CIC) were also significantly higher. However, the levels of HBsAg CIC did not correlate with the degree of proteinuria or hematuria. In patients with persistent HBaAg carriage, serum HBeAg status alone did not correlate with remission rate, and remission occurred usually before the HBeAg seroconversion to anti-HBe. These results suggest that factors other than HBeAg play important roles in HBVMN.

Antigen-Antibody Complex

[Immunological profile of workers occupationally exposed to chlorine].

Immunological profile of 42 men working under exposure to chlorine for a period from 2 to 38 years was analysed. Toxicological analyses of air samples which were carried out for 20 years showed similar chlorine concentration ranging from 0.21 to 1.05 mg/m3. The number of B, T, and non-B, non-T lymphocytes was determined as well as the C3c, C4 complement components and proteins of acute phase reaction: alpha 1-acid-glycoprotein, haptoglobin and ceruloplasmin in the serum. Chronic exposure to chlorine produced a stimulating effect on the immune system, which was manifested by elevated IgA, IgD and IgM levels, the concentration of acute phase reaction proteins and increased number of B lymphocytes. The observed phenomenon had no influence on the antibacterial and anticancer immunity of the workers.

Adult

Immunologic profiles of adults with congenital bleeding disorders.

An immunologic profile may be useful to predict the development of Acquired Immune Deficiency Syndrome (AIDS) in both high risk patient groups including homosexuals, hemophiliacs, Haitians, and users of illicit intravenous narcotics as well as the general population. We evaluated 76 consecutive, apparently healthy, adults with congenital bleeding disorders for serum beta-2 microglobulin concentration by competitive enzyme immunoassay, T-lymphocyte subpopulations with monoclonal antibodies and serum interferon by inhibition of vesicular stomatitis virus plaque forming units. Findings on physical examination were remarkable with 24% of the group having longstanding splenomegaly and 24% lymphadenopathy. beta-2 microglobulin levels were 3232 +/- 220 micrograms/l (mean +/- SEM) with normal controls 2134 +/- 119 micrograms/l. The ratio of Leu3a (helper/inducer) positive to Leu2a (suppressor/cytotoxic) positive T-lymphocytes was 1.33 +/- 0.1 (mean +/- SEM, median = 1.18). Normal control ratios were all greater than 1.35 with a mean +/- s.d. = 1.96 +/- 0.28. Abnormal ratios of T-lymphocyte subpopulations appeared to persist over time. Increases in beta-2 microglobulin correlated with an inverted helper/suppressor T-lymphocyte ratio, the presence of lymphadenopathy, and elevations in aspartate aminotransferase. Interferon was detected in 18% of patient sera. More frequently transfused and more severely affected patients had a higher frequency of immunologic abnormalities although abnormalities also occurred in some rarely and never transfused less severely affected patients. These studies document a high incidence of immunologic abnormalities in patients with inherited coagulation defects.

Acquired Immunodeficiency Syndrome

Biological and immunological characterization of human luteinizing hormone: IV. Biological and immunological profile of two international reference preparations after electrofocusing.

The first IRP of Human Pituitary Gonadotrophins (FSH/LH) for bioassay (69/104) and the 1st IRP of Human Pituitary Luteinizing Hormone (LH) for immunoassay (68/40) were fractionated by an electrofocusing technique in a sucrose density gradient and the profile of biological and immunological activities was determined. The partially purified LH preparation (69/104) gave a broad pattern of biolgical and immunological activities which extended from pH 4 to 10. The biological : immunological (B/I) ratio of the various fractions (using the 68/40 preparation as standard) ranged from 0.04 to 1.05. The low B/I ratios indicate the presence of high levels of immunologically active, biologically inactive material in this preparation. In contrast to the behaviour of the 69/104 preparation, the major proportion (88%) of the biological activity recovered after electrofocusing of the highly purified LH preparation (68/40) was found within the pH range 7--9, with B/I ratios (again using as standard the 68/40 preparation) ranging from 0.4 to 1.5. Multiple dose parallel line design radioimmunoassays revealed a lack of parallelism between the 69/104 and 68/40 International Reference Preparations. This was attributed to the presence of acidic material in the former preparation, which is practically absent from the latter. The biological LH profiles of both the 69/104 and 68/40 preparations differed from those previously reported for aqueous extracts of pituitaries. It is concluded that the dissimilarity in the electrofocusing profiles of the biological and immunological activities of the 69/104 preparation renders this preparation unsuitable as a reference preparation for the quantitation of biologically active LH by radioimmunoassay methods. Using the same criteria, the 68/40 preparation would appear to be a more suitable standard.

Animals

[Inhibitory and immunological profile of therapeutic serum protein solutions].

Biseko is prepared from pooled human plasma by specific stepwise adsorption of the coagulation factors avoiding spontaneous coagulation. Biseko is manufactured from pooled plasma from more than 1000 donors. In order to ensure its hepatitis safety, the starting plasma is cold sterilized by beta-propiolactone and UV-irradiation. The inhibitory and immunological profile of the cold sterilized Biseko was compared with another commercial serum preserve and normal serum. alpha 1-antitrypsin, alpha 2-macroglobulin and antithrombin III are present in Biseko and normal serum in their biologically active forms. A certain amount of the opsonin, fibronectin, is heparin-precipitable in normal serum and has thus retained its native character, while the fibronectin in the commercial serum preserve examined is not heparin-precipitable. Biseko contains fibronectin only in trace amounts. The IgG, IgA and IgM immunoglobulin concentrations and activities in the serum preserves are equivalent to those in normal serum. One major difference between normal serum and the cold sterilized Biseko is that metabolites from the coagulation pathways are absent in Biseko. Normal serum is not suitable for therapeutic purposes because of activated enzymes formed during coagulation. The chemical analysis of the protein pattern in Biseko resembles more fresh frozen plasma without coagulation factors than normal serum.

Blood Proteins

The immunological profile in sickle cell anaemia: a study of patients in the Arab Peninsula.

Recurrent and often serious infections are common in sickle cell anaemia. The predisposing causes are multiple, and immune abnormalities are frequently blamed. In this study, immune complexes, lymphocyte subpopulations, immunoglobulins and complement were determined in 40 Arabs with sickle cell anaemia to ascertain some aspects of their immunological profile. Immunoglobulins were found to be either normal or high, C3 and C4 values mostly clustered at the lower level of normal with a few values below normal, and some patients had low T4/T8 lymphocyte ratios. The results are discussed and compared with previous studies.

Adolescent

Immunological profile in neonatal hyperbilirubinemia.

Thirty cases of neonatal hyperbilirubinemia of varying etiology, severity and duration; and twenty six normal healthy newborns were subjected to various tests of cellular and humoral immunity. The results revealed a significant depression of all the parameters of cellular immunity in neonatal hyperbilirubinemia of greater than or equal to 10 mg/dl as compared to the control values. The depression of immunological profile in these newborns was seen to be more pronounced with increasing duration and severity of jaundice. A limited assessment of the humoral immunity by the B cell count and serum immunoglobulin IgG levels, however, showed no significant difference from the control.

B-Lymphocytes

[Early diagnosis and surveillance of congenital toxoplasmosis. The comparative immunological profiles method].

More than 8000 samples (sera, cord blood, CSF, etc.) from patients who had, or were likely to have, toxoplasmosis were studied by the CIP-ELIFA technique. The first stage in this technique is immunoelectrodiffusion on a microporous cellulose acetate membrane. In the second stage, immunodetection and isotypic characterization of the precipitating systems are rapidly carried out by immunofiltration with anti-IgG, IgM, IgA or IgE-labelled antibodies (enzyme-linked immunofiltration assay or ELIFA). Several samples are jointly laid out on the same membrane for compared immunological profiles (CIP). When applied to the mother-foetus relationship in toxoplasmosis, this procedure provides an early diagnosis of congenital infestation in 85% of the cases. Positive criteria are based on evidence of specific IgM, IgE or IgA in the child, but also on the detection of foetal or neonatal antitoxoplasmosis IgG which can be distinguished from the IgG transmitted by the mother. Polyisotypic supervision is of considerable value for assessment of prognosis and of therapeutic effectiveness at the end of treatment. Satisfactory isotypic characterization can only be achieved by using particular functional antigens.

Antibodies

[Relevant immunological profiles].

In 1980 more than 200,000 immunological tests were performed in the Section of Clinical Immunology, Department of Medicine, University Hospital, Zurich (Switzerland), a fact which raises the question whether the results warrant the effort involved. To answer this question of clinical relevance, 4 disease complexes have been investigated: lupus erythematodes, systemic affections dominated by arthralgia, hepatitis and thyroiditis. The analysis shows that no single factor but only an optimized set of tests is capable of distinguishing between related diseases. Follow-up studies are of prime importance because the sequence of antigen expression and antibody responses provides valuable additional information. Laboratory results can be evaluated only in conjunction with the clinical picture.

Aged

Immunological profile of chest x-ray-negative, asymptomatic asbestos workers.

Several immunologic parameters, both humoral and cellular, were studied in the serum and peripheral blood lymphocytes derived from chest x-ray-negative, asymptomatic asbestos workers. All humoral and cellular parameters were intact, except the con-A-induced T cell suppressor activity and T cell division in autologous mixed lymphocyte reaction, which were significantly elevated in the asbestos plant workers. The significance of these increased T cell activities in asbestos exposed people is not clear, and further clinical and immunological follow-up is warranted.

Antibodies, Antinuclear

Immunologic profiles of cats with persistent, naturally acquired feline leukemia virus infection.

Several immunologic responses were measured in 13 healthy cats with naturally acquired, persistent feline leukemia virus (FeLV) viremia from 4 multiple-cat households and were compared with responses from 28 of their healthy, non-FeLV-viremic housemates. Significant differences (P = less than 0.05) were not observed between results of FeLV-viremic and nonviremic cats for peripheral blood leukocyte or lymphocyte count, percentage of peripheral blood mononuclear cells able to form rosettes with guinea pig RBC or with antibody- and complement-coated sheep RBC, lymphocyte proliferative response to concanavalin A or pokeweed mitogen, or serum immunoglobulin G concentration. Seemingly, persistent FeLV viremia, when naturally acquired, may exist for some time without lymphopenia or a marked loss of mitogen-induced lymphocyte proliferation.

Animals

[Changes in the immunologic profile of newly-diagnosed diabetic patients during the first year of the disease].

Immunological markers including ICA-IgG, CF-ICA, other non organ specific autoantibodies, circulating immune complexes (CIC), IgG, IgA, IgM, C3, C4 and lymphocyte subpopulations (OKT3, OKT4, OKT8) were studied at onset in 32 insulin dependent diabetic patients (16 males, 16 females, aged 1-21 yr.). Other non organ specific autoantibodies, CIC, IgG, IgA, IgM, C3, C4 and OKT3, OKT4, OKT8 were also studied after a 6-12 months follow-up in the same group of patients. ICA-IgG and CF-ICA were also studied in a control group of 19 insulin dependent diabetic patients with an over 3 year history of diabetes. ICA IgC, CF-ICA, other autoantibodies and CIC were detected at diagnosis in 65%, 19%, 33%, and 50% of patients respectively. ICA-IgG and FC-ICA were detected respectively in 15% and zero of the control group of 19 long standing diabetes. No alterations in IgG, C3 and C4 levels and in T cells subsets have been found at onset. C4 levels significantly decreased at the successive observation. A significant elevation of IgG levels and helper/suppressor ratio were also observed at follow-up. Autoantibodies and CIC positive sera at diagnosis support the concept that a previous autoimmune disorder exists before clinical manifestations of diabetes. Other immunological abnormalities including relative hypogammaglobulinemie, lower C4 and higher helper/suppressor ratio, observed by other authors (Kanakoudi 1984, Vergani 1985, Lernmark 1985) represent an aspecific alteration due to metabolic imbalance or to an earlier immunological disorder.

Adolescent

alpha-Interferon therapy in patients with chronic active hepatitis B: immunological profile.

The effect of interferon-alpha 2b (IFN) on viral markers, liver function and immunological parameters (CD3, CD4, CD8, B, NK, II-2 receptor and HLA-DR positive cells in blood and T cell proliferation) was studied in 9 patients with HBsAg(+), HBeAg(-) chronic active hepatitis (CAH). Three patients were HBV-DNA(+) and 6 also had complications of cirrhosis of the liver (LC). IFN was given at a dose of 2.5 mil IU x 3 weekly for 6 months. One patient with LC developed hepatic coma and died 2 months later. Severe leukopenia limited duration of treatment to 2 and 4 months in another 2 patients. By the end of treatment, the 8 patients were in good clinical status, SGOT, SGPT levels and prothrombin time were decreased, HBV-DNA became negative in 2 out of 3 patients and proportions of CD3, CD4, B, NK and activated cells were significantly decreased. When compared to controls, NK and activated cells were significantly increased in patients before and were gradually decreased by the end of treatment. In contrast, T transformed cells were significantly decreased before and ranged in normal levels by the end of treatment. These findings suggest that immunomodulatory activity possibly contributes to the beneficial effect of IFN therapy.

Adult

[Immunological profile of Whipple's disease evolving over a period of 17 years].

This report describes an immunological study made on a 58 years old patient with a Whipple disease diagnosed in 1969 and treated with different antibiotics. All attempts to stop the antibiotherapy resulted in reappearance of clinical symptoms. Further, this patient suffered anguillulosis infection in 1954 and this persists despite thiabendazole therapy, as shown by periodical creeping lunear dermatitis (larva currens). Laboratory investigations displayed low IgM levels and lack of cutaneous reactivity to conventional antigenic challenge. In vitro studies on granulocyte and monocyte phagocytic activity did not display any clearcut deficiency. Finally, this patient displayed peripheral lymphopenia and decrease of the T4+ (CD4) lymphocyte subpopulation. The proliferative response of lymphocytes to phytohemagglutinin stimulation (a cellular T-cell function) was drastically decreased in assays performed during the 16 month duration of patient's exploration. This proliferative defect seems to be due to increased PGE2 release (a 3-5 fold increase was demonstrated), resulting in inhibition of interleukin 2 (IL2) synthesis and activity. Further, patient's lymphocyte normally expressed IL2 receptor. When the B lymphocyte dependent humoral response was assayed, normal B lymphocyte differentiation into plasmocytes was found. However the pokeweed mitogen induced proliferative response of B lymphocyte displayed major decrease in four sequential tests. This might be due to a lack of B cell growth factor (BCGF) activity, since this interleukin involved in T lymphocyte, B lymphocyte cooperation was not found in supernatants of patient's cell. Further, interleukin 1 (involved in macrophage lymphocyte cooperation) was normally produced. In conclusion, no deficiency of in vitro phagocytose was demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Differentiation

Immunological profile of patients with recurrent respiratory infections.

The authors present an analysis of the results of laboratory immunological examination of 52 patients suffering from recurrent respiratory infections. Besides the typical laboratory correlates of chronic inflammation, several findings indicated the depressed function of cellular and partially humoral immunity. The immunological parameters, most frequently decreased in comparison with normal values, were as follows: the response to the recall antigens of Imunoskintest (lower in 54% of patients), the relative number of CD3+ lymphocytes (35%), the CD4/CD8 ratio (37%), phagocytic activity (37%) and also serum IgA (12%). This means that more than two thirds of patients displayed at the time of examination a substantial alteration of one or more immunological parameters, the depression of cellular immunity was much more pronounced. It is concluded that the laboratory immunological examination of patients with recurrent respiratory infections is very important for revealing of an underlying cause of the disease and for indicating the adequate immunomodulatory treatment.

Adult

Combined evaluation of circulating immune complexes and antibodies to Pseudomonas aeruginosa as an immunologic profile in relation to pulmonary function in cystic fibrosis.

We developed a solid-phase radioimmunoassay with a reference standard pseudomonas antigen and used this with 125I-labeled anti-human immunoglobulin to evaluate specific antibodies to Pseudomonas aeruginosa, qualitatively and quantitatively, in sera from children with cystic fibrosis (CF) whose lungs were colonized by this bacterium. The results of this IgG assay correlated with the number of precipitin antibodies to the standard reference antigen determined by cross-immunoelectrophoresis in the same sera. Forced expiratory volume (FEV1; percentage predicted), determined as an indicator of lung injury in CF, was evaluated as an immunologic response to pseudomonas, against a profile derived from combined serial data on both the circulating immune complexes (CIC) and the Ps. aeruginosa antibodies (N = 25 CF patients; 108 sera). This revealed that in CF patients who had no specific IgG antibodies to Ps. aeruginosa and no IgG-CIC had the best pulmonary function (FEV1 = 115 +/- 14.52%) and those with high levels of antibodies to this organism and high IgG-CIC levels had the poorest lung function (FEV1 = 69.75 +/- 10.99%) (P less than 0.05). We believe that this indicates an immunologic basis for lung injury in cystic fibrosis.

Antibodies, Bacterial

[Immunologic profile of patients with carcinoma of the colorectum in the aged].

The authors, after explaining why they were persuaded to effect a study about the immunological outline of patients in geriatric age, suffering from colorectal carcinoma in different stages, state the methods they adopted for the in vivo and in vitro study of the cellular and humoral immunity. In order to better characterize these subjects, the authors also dosed tumoral markers, specific enough for the large intestine carcinoma, such as CEA and AFP. After reporting the results of their research, the authors, as a conclusion, assert there is certainly a straight correlation between immunity faults, bound to ageing, and neoplastic disease; therefore, the study of the immunological outline in aged patients is very useful, not only for prognostic purposes, but also to monitoring the immunitary state, mot inclined to meet depression in such patients as a consequence of the different therapies performed.

Age Factors