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PubMed2005

Dose dependence of immunological response to sublingual immunotherapy.

BACKGROUND: Sublingual-swallow immunotherapy (SLIT) is an accepted treatment for allergic rhinitis but its optimal dosage is scantly investigated. We studied the dose dependence of clinical efficacy and immunological response to SLIT by administering two different dosages of the same allergen in rhinitic children monosensitized to grass pollen. METHODS: Seventy-one patients with comparable age and symptoms were randomized to receive SLIT by the same grass pollen extract from Stallergenes (Antony, France), 40 of them with the 100 IR and 31 with the 300 IR extract. All patients recorded diary cards for symptoms, medications and side-effects of the treatment, and had measurements of specific IgE and IgG4 in serum by the CAP System FEIA (Pharmacia, Uppsala, Sweden) and in nasal secretion by an in situ incubation method with the same reagents of CAP System FEIA. RESULTS: Symptom/medication scores during the pollen season were significantly higher in patients treated with the lower dosage compared with those treated with the 300 IR dosage. Side-effects occurred with a comparable rate (25.8%vs 27.5%) in the two groups. Serum-specific IgE and IgG4 had no significant changes after 3 months of SLIT in both groups, while a significant seasonal increase of nasal IgE (P = 0.015) and IgG4 (P = 0.019) was found only in patients treated with the lower dosage. CONCLUSIONS: A rise of specific IgG4 and a blunting of seasonal increase of specific IgE in serum was repeatedly reported during subcutaneous immunotherapy (SCIT) with pollen extracts. Our findings show such blunting of specific nasal IgE along with a low symptom/medication score in patients treated with SLIT with the higher dosage, but not a concomitant rise of specific nasal IgG4. This suggests a local immunological effect of SLIT, different from systemic mechanisms of SCIT.

Administration, Sublingual↗
PubMedDate not supplied

Effects of local prostatic hyperthermia on human NK and T cell function.

Studies on lymphocyte subsets, mitogen transformation and NK cytotoxicity of blood mononuclear cells (BMNC) were performed in 30 patients who received transrectal microwave hyperthermia (TRHT) of the prostate. Of the 30 patients, 15 had advanced adenocarcinoma of the prostate (CAP) and 15 had severely symptomatic benign prostatic hyperplasia (BPH). Local TRHT was given twice a week for a total of six sessions. The treatments were administered at 2450 MHz or 434 MHz using a water-cooled rectal applicator. Each TRHT session lasted for 30 min at steady-state temperature controlled on the rectal mucosa at 45 degrees C. Studies of immune reactions were performed before TRHT, at the completion of six TRHT sessions, and at 1, 2, 4, and 6 months from therapy. Identical studies at the same time-interval were performed in 30 healthy male volunteers. In the 15 CAP patients the results of the immune studies obtained before TRHT, including CD4+/CD8+ ratio, PHA and Con-A transformation indices were significantly lower (p less than 0.01) than in the 15 BPH patients and in the 30 normal volunteers. The 15 BPH patients and the 30 normal volunteers all had immune parameters within the normal limits. Following the administration of TRHT in the 15 CAP patients, a transient significant (p less than 0.01) stimulation of the tested cell-mediated immune parameters was observed when compared with the pretreatment values. The peak effect of this stimulation was noted at 2 months with a subsequent decrease. In the 15 BPH patients a lesser degree of immune stimulation was noted. As expected there was no substantial change in the measured cell-mediated immune parameters in the 30 normal volunteers. A significant increase of NK cytotoxic activity was noted following TRHT in CAP patients when compared with the pretreatment results. This activity reached 120-130% of the individual initial values, being significant at p less than 0.01. The finding of transient stimulation of cell-mediated immune reaction, following local hyperthermia in patients with CAP, may be of some clinical relevance and of clinical importance. Additional studies are being formulated to confirm these interesting findings.

Adenocarcinoma↗
PubMed1978

Alloantigens determined by a second D region locus elicit a strong in vitro cytotoxic response.

The newly defined L antigen (previously designated D') has been studied with the CML assay. Balb/c-H-2db mice, which carry a loss mutation in the D region, were found to generate anti-L cytotoxic effector cells when stimulated with wild-type (BALB/c) cells. When the target cells were treated with an antiserum against L, cytolysis by BALB/c-H-2db anti-BALB/c effectors was completely blocked. However, an antiserum against D, the antigen that bears the D region private specificity, had no effect on the anti-L cytotoxic response. In a control CML experiment that was specific for the D antigen, the antiserum to L had no effect, whereas the antiserum to D blocked completely. These results indicate that the L and D antigens are recognized in a CML response as separate entities on the cell surface. In an allogeneic response to the products of the D region, cytotoxic effectors were generated that were specific for L in addition to those specific for D. This conclusion was supported by blocking experiments with either antisera or unlabeled targets. These functional studies thus extend previous co-capping and immunochemical studies, and further support the hypothesis that L is a third transplantation antigen similar to the K and D antigens.

Animals↗
PubMed1986

Herpes simplex virus expressing Epstein-Barr virus nuclear antigen 1.

DNA fragments containing an open reading frame known to encode most or all of the EBNA1 protein of Epstein-Barr virus (EBV) were fused in the proper transcriptional orientation to the promoter regulatory domain, capping site, and a portion of the 5' transcribed noncoding sequences of the HSV-1 alpha 4 gene of herpes simplex virus 1 (HSV-1). In these constructs 20, 130, or 385 bp of EBV DNA and 28 bp of HSV-1 DNA separated the alpha 4 cap site from a putative initiator codon of the EBNA1 gene. The chimeric alpha 4-EBNA1 genes were introduced into L cells or recombined into the viral genome using the thymidine kinase selection system. The three chimeric gene constructs resident in the L cell clones expressed a protein indistinguishable from authentic EBNA1 with respect to electrophoretic and immunologic properties indicating that the ATG at the beginning of the EBV open reading frame initiated translation of the bonafide EBNA1 protein. The chimeric alpha 4-EBNA1 genes resident in L cells were induced by HSV-1 infection and were regulated as alpha genes. The chimeric alpha 4-EBNA1 gene recombined into the viral genome was also regulated as an alpha gene. The recombinant viruses were stable and expressed 50- to 100-fold more EBNA1 than is ordinarily expressed in human lymphocytes carrying the EBV genome. EBNA1 did not alter the program of HSV-1 protein expression. The utility of the vector is discussed.

Animals↗
PubMed1979

HLA, DRW (IA-like) and additional surface antigens expressed on adenoid T and B lymphocytes.

Pregnancy sera were found to react differently when screened simultaneously with adenoid and peripheral blood lymphocytes (PBL) obtained from the same individual. Some of the reactions were attributed to the higher sensitivity of adenoid lymphocytes to a low titer HLA or Ia antibody, while others were shown to be due to the expression of DRw (Ia-like) antigens on both T and B lymphocytes separated from adenoids. Positive reactions specific to adenoid lymphocytes, or manifested only following anti-beta2-microglobulin (a-beta2-m) treatment, suggest the presence of antigens other than HLA or Ia on the cell membrane. Unmasking of antigenic sites by the a-beta2-m capping process and rearrangement of the membrane structure may also contribute to the observed phenomena.

Adenoids↗
PubMed2005

Comparison of VIDAS Stallertest and Pharmacia CAP assays for detection of specific IgE antibodies in allergic children.

In vitro determination of specific IgE antibodies in serum is the most frequently used method, besides the skin test, for diagnosing allergies. Standardized and reproducible assays of specific IgE antibodies contribute to the quality of diagnosis and treatment of allergic disease. This study compared the results and performance characteristics of the Pharmacia CAP system and a new specific IgE method using the VIDAS Stallertest (manufactured by bioMériux). To evaluate their clinical efficiency, the results of the CAP and VIDAS Stallertest assays were compared with skin prick test (SPT) results. After allergic patients completed SPTs, serum samples were collected and CAP and VIDAS Stallertest assays were performed to determine specific IgEs for Dermatophagoides farinae, D. pteronyssinus, cockroach, and alternaria. For egg and milk, we measured only the correlation between the 2 in vitro assays. When SPT was used as a reference standard, the sensitivity and specificity of the CAP assay was a little higher in respect to all inhalant allergens. There were significant correlations between the results of VIDAS Stallertest and CAP assays for IgE antibodies to inhalant and food allergens. This study indicates that the VIDAS Stallertest and Pharmacia CAP assays are feasible and replicable for measuring allergen-specific IgE.

Adolescent↗
PubMed1989

Experimentally induced ocular chlamydial infection in infant pig-tailed macaques.

Four Macaca nemestrina monkeys were inoculated in the conjunctiva with Chlamydia trachomatis (strain E) at 6 weeks of age. A fifth monkey was inoculated with HeLa cell materials only. Ten weeks later, all monkeys were reinoculated with either strain E or strain C. All inoculated monkeys were susceptible to infection with C. trachomatis as documented by fluorescent antibody staining of smears and reisolation of the organism from conjunctival and nasopharyngeal swab specimens. Rectal and vaginal swab specimens remained negative throughout the study. Three of four inoculated animals responded with IgM titers reaching a peak of 1:16 (M#3) and 1:32 (M#1, M#4) 2 weeks after the primary inoculation. IgG appeared in all inoculated animals and titers rose to peak levels of 1:64 (M#2), 1:128 (M#1, M#3), and 1:256 (M#4). Histopathology documented a dramatic difference in immunological response following secondary inoculation. Primary inoculation elicited a typical inflammatory response characterized by moderate stromal infiltration of polymorphonuclear and mononuclear leukocytes. Plasma cells appeared by week 3 postinoculation (pi). Following a secondary inoculation, classic follicle formation was evident by 1 week pi. Mononuclear markers identified a germinal center composed of B cells and a T cell cap. Epithelial thinning near the cap of the follicle was accompanied by a complete loss of goblet cells. This model may be useful for studying the immunopathology of infant chlamydial infections.

Animals↗
PubMed2003

Natural N-terminal fragments of brain abundant myristoylated protein BASP1.

BASP1 (also known as CAP-23 and NAP-22) is a novel myristoylated calmodulin-binding protein, abundant in nerve terminals. It is considered as a signal protein participating in neurite outgrowth and synaptic plasticity. BASP1 is also present in significant amounts in kidney, testis, and lymphoid tissues. In this study, we show that BASP1 is accompanied by at least six BASP1 immunologically related proteins (BIRPs), which are present in all animal species studied (rat, bovine, human, chicken). BIRPs have lower molecular masses than that of BASP1. Similarly to BASP1, they are myristoylated. Peptide mapping and partial sequencing have shown that BIRPs represent a set of BASP1 N-terminal fragments devoid of C-terminal parts of different length. In a definite species, the same set of BASP1 fragments is present in both brain and other tissues. The sum amount of the fragments is about 50% of the BASP1 amount in a tissue. Obligatory accompanying of BASP1 by a set of specific fragments indicates that these fragments are of physiological significance.

Animals↗
PubMed1993

XrpFI, an amphibian transcription factor composed of multiple polypeptides immunologically related to the GA-binding protein alpha and beta subunits, is differentially expressed during Xenopus laevis development.

XrpFI, first identified in the extract of Xenopus laevis oocyte nuclei, binds to a proximal sequence of the L14 ribosomal protein gene promoter. Its target sequence, 5'-TAACCGGAAGTTTGT-3', is required to fully activate the promoter, and the two G's of the central motif are essential for factor binding and transcriptional activation; our data also suggest that XrpFI may play a role in cap site positioning. The binding site of XrpFI is homologous to the sequence recognized by the family of ets genes. Antibodies specific for Ets-1 and Ets-2 proteins did not react with XrpFI, but those raised against the rat alpha and beta GA-binding proteins both supershifted the retarded bands formed by XrpFI. The Xenopus polypeptides related to GA-binding protein alpha interact with DNA both as monomers and as heterodimers associated with beta-related proteins. Oocyte nuclei contain multiple forms of alpha- and beta-related proteins: the alpha-like proteins remain throughout development, while the pattern of the beta species changes in the embryonic stages examined. beta-like proteins are undetectable in the cleavage period up to the neurula stage, but at later stages, when ribosomal protein genes are actively transcribed, two beta-related polypeptides reappear.

Animals↗
PubMed1975

Immunologic injury in measles virus infection. II. Suppression of immune injury through antigenic modulation.

Upon the addition of antibody to measles virus, measles virus antigens expressed on the surface of infected cells can be modulated from the cell's membrane in vitro. Removal of measles virus antigens from the surface of cells occurs relatively rapidly and is accompanied by a parallel reduction in the ability of antibody and complement to lyse these cells. Modulation of surface viral antigens can occur in the absence of cap formation and is fully reversible once measles virus antibodies are removed from culture medium. Protracted exposure of acutely infected cells to measles virus antibodies results in a population of cells that exhibit normal cytomorphology and growth behavior. These cells continue to express measles virus antigens internally, but not at the cell surface, and are refractory to immune lysis. Once antiviral antibody is removed, measles virus antigens again appear on the cell surface, giant cell and syncytial formation occur, and cell death follows. These observations may explain the persistence of virus in spite of a vigorous host antiviral immune response in certain chronic infections of man.

Antibodies, Viral↗
PubMedDate not supplied

Occupational asthma caused by grass pea used in the industrial processing of parquet.

BACKGROUND: although grass pea belongs to the leguminoseae family, allergic reactions to its flour have rarely been described. Clinical and immunological studies were performed to confirm a type I hypersensitivity mechanism in a case of occupational asthma to grass pea flour exposure, used in the industrial processing of parquet. METHODS: occupational asthma was diagnosed according to patient history, PEFR monitoring and a specific bronchial challenge test. Skin prick test with an aqueous grass pea flour extract, specific IgE determinations (CAP assay) and IgE immunoblot tests were performed. RESULTS: skin prick test with the extract showed a positive immediate response, and negative response in controls. Specific IgE to grass pea was positive (9.57 KU/l). Immunoblotting demonstrated the presence of specific serum IgE that recognized 3 proteins in the extract (MW 46, 32 and 28 kDa). PEFR monitoring showed positive results. Bronchial challenge test with the extract elicited an isolated immediate response. CONCLUSIONS: as far as we know this is the first time that IgE mediated occupational asthma caused by grass pea is reported and it is also the first time that its allergens are characterized. Grass pea flour might constitute a relevant occupational allergen in this unreported source of exposure in parquet manufacturers.

Adhesives↗
PubMed2007

Intestinal involvement secondary to the antiphospholipid syndrome (APS): clinical and immunologic characteristics of 97 patients: comparison of classic and catastrophic APS.

OBJECTIVE: To analyze the clinical and laboratory characteristics of 97 patients with intestinal involvement secondary to the antiphospholipid syndrome (APS) (37 patients with classic APS and 60 with catastrophic APS). METHODS: A computer-assisted (PubMed) search of the literature was performed to identify all cases of intestinal involvement associated with the APS from 1983 to December 2005. In addition, we analyzed the web-site-based international registry of patients with catastrophic APS ("CAPS Registry"). RESULTS: There were no differences in distribution by gender, mean age, and previous clinical manifestations of APS between the 2 groups. The prevalence of abdominal pain as the presenting manifestation of intestinal ischemia was higher in patients with classic APS (76% versus 37%; P < 0.005). The main difference in histopathologic findings between the 2 groups was the higher rate of microthrombosis in patients with catastrophic APS (75% versus 4%; P < 0.0005). The mortality rate was higher in patients with catastrophic APS (55% versus 17%; P < 0.0005). Follow-up was available in 22 patients with classical APS: 17 of them were discharged on oral anticoagulation and with a mean follow-up of 13 months (range, 1 to 48); all were in good health without the development of new thrombotic events. CONCLUSIONS: Intestinal involvement, although infrequent, is an important complication in patients with APS, especially in those with catastrophic APS. This would support the need for systematic screening for aPL in all cases of mesenteric thrombosis or ischemic colitis without clear underlying predisposing factors, and for systematic screening procedures in all classic APS patients complaining of abdominal pain.

Adolescent↗
PubMedDate not supplied

In vitro sperm capacitation and intrauterine insemination (IVC-Insem): a simple technique for the treatment of refractory infertility unrelated to female organic pelvic disease. Clinical results and immunological effects: a preliminary report.

12 couples, with infertility due to male subfertility, female antisperm isoimmunization, male antisperm autoimmunization, cervical mucus insufficiency or unexplained infertility underwent intrauterine A.I.H. with capacitated sperm and controlled ovarian stimulation. The pregnancy percentage was of 41.6% per woman treated and of 31.2% per treatment cycle; five pregnancies were obtained, of which two resulted in abortions. Five cases of oligoasthenospermia were treated, three severe and two moderate; two pregnancies occurred in the former and one in the latter. S.I.T. and S.I.T.-cap. were performed on the serum, and Micro-S.I.T. and Micro-S.I.T.-cap. on the cervical mucus in order to exclude the possibility that intrauterine A.I.H. with capacitated sperm might have caused capacitated or non-capacitated antisperm immunization. Intrauterine A.I.H. would seem to be a useful alternative to G.I.F.T. and to I.V.F./E.T. or at least a technique which should be performed before these two in cases of infertility not caused by female organic pelvic disease; it is cheap, simple and extremely well-accepted by the patient.

Adult↗
PubMed1998

Asthma caused by Ficus benjamina latex: evidence of cross-reactivity with fig fruit and papain.

BACKGROUND: Ficus benjamina or weeping fig is a plant used increasingly for indoor decoration that can cause allergic rhinitis and asthma. OBJECTIVE: We report a clinical and immunologic study in a patient with perennial asthma caused by F. benjamina latex in whom several episodes of angioedema of the oropharyngeal tract and tongue followed ingestion of figs and kiwi. METHODS: Hypersensitivity to latex from F. benjamina and from Hevea brasiliensis, fig fruit, kiwi, papain, and bromelain was investigated by means of skin prick test, specific IgE determination by CAP, histamine release test, and bronchial provocation test to F. benjamina latex. CAP-inhibition assays were carried out to study possible cross-reactivity among these antigens. RESULTS: Hypersensitivity to F. benjamina latex, fig, kiwi, and proteases was demonstrated by means of skin prick test, determination of specific IgE and histamine release test. Bronchial provocation test with F. benjamina latex resulted in a dual asthmatic reaction, confirming the etiologic role of this plant. A rise of eosinophil cationic protein in patient's serum was observed 21 hours after bronchial challenge, suggesting activation of eosinophils. Inhibition assays showed that F. benjamina latex as liquid-phase inhibited up to 95% the CAP to fig and up to 57% the CAP to papain. Neither sensitization nor cross-allergenicity with H. brasiliensis latex was found. CONCLUSIONS: Hypersensitivity to F. benjamina latex may cause IgE-mediated respiratory allergy. The association with allergy to fig and papain is likely due to the existence of cross-reactive allergen structures.

Adult↗
PubMed1993

Interaction of immunologically-active lipopeptides with membranes.

Synthetic tripalmitoyl-S-glycerylcysteinyl (Pam3Cys) peptides are derived from the N-terminal part of bacterial lipoprotein and constitute polyclonal B-lymphocyte and macrophage activators. In order to elucidate the primary events of leukocyte activation, we investigated the biophysical interaction of lipopeptides containing spin labels or fluorescent markers with phosphatidylcholine vesicles or immune cells. Utilizing fluorescence microscopy and FACS analysis we found, that the surface of cells, after incubation with a fluorescein-labelled lipopeptide, was highly fluorescent. In addition, capping and patching was observed. Furthermore, fluorescence quenching experiments and electron paramagnetic resonance studies using vesicles incubated with lipopeptides suggested, that the peptide moiety and other more polar molecules linked to the lipo-amino acid are exposed to the hydrophilic compartment. These results show that in lipopeptide conjugates the Pam3Cys moiety acts as an efficient membrane anchor for molecules covalently coupled to it. The sequestering of the fatty-acid chains of the lipopeptide within the membrane is an early step of interaction, which might induce the uptake of the lipopeptide into the cell and the stimulation of immunocompetent cells.

Amino Acid Sequence↗
PubMed1979

Antibody-induced changes in levels of cyclic adenosine monophosphate in leukaemic lymphocytes.

When L2C leukaemic B lymphocytes from guinea-pigs were incubated in vitro with antibody directed to their surface immunoglobulin (Ig), a rapid rise in intracellular adenosine 3':5'-phosphate (cyclic adenosine monophosphate, cAMP) was observed. Estimation of cAMP was by a protein-binding assay using bovine adrenal protein kinase. Increases up to 30-fold occurred within 30 seconds of incubation at 37 degrees C, to be succeeded by a fall which reached the basal level between 5 and 7 min. The response was proportional to the amount of antibody present. Cross-linking of surface Ig by the antibody was necessary, bivalent (Fab'gamma)2 from the antibody gave a rise in cAMP similar to that given by the parent molecule, whereas monomeric Fab'gamma was ineffective unless it was subsequently cross-linked by anti-antibody. The rise was too rapid to have required capping of the surface Ig for its induction. Not all perturbations of the plasma membrane by antibody induce such a surge in cAMP, since anti-beta2 microglobulin, also reacting with the lymphocyte surface, failed to alter cAMP concentration. The results emphasize that immunotherapy can be influenced by antibody altering the metabolic activity of target cells, quite apart from activation of immunological cytotoxic pathways.

Animals↗
PubMed2005

Enhancing the etiologic diagnosis of community-acquired pneumonia in adults using the urinary antigen assay (Binax NOW).

OBJECTIVES: Approximately 40% of community-acquired pneumonia (CAP) remains of unknown etiology. To improve the rate of detection of the causative microbiologic agent, the Binax NOW Streptococcus pneumoniae urinary antigen test (UAT) was evaluated. DESIGN: In this prospective study, 67 adults with CAP were compared with 81 healthy patients to determine sensitivity and specificity of the UAT and its role in improving the etiologic diagnosis of CAP. RESULTS: An etiology could be found for 22 patients (33%) using conventional methods (14 S. pneumoniae, sensitivity 64.3%, 1/81 positive UAT control urine samples, specificity 98.8%). This proportion increased to 33 patients (49%) with the addition of the urinary antigen test (p = 0.039). Pneumococcal infection was diagnosed by the UAT in 24% of our patients without an etiologic identification by conventional methods. CONCLUSIONS: Given its excellent specificity, this test can be considered an important tool for detecting S. pneumoniae in CAP of unknown etiology, enabling the diagnosis of pneumococcal pneumonia in a quarter of cases.

Adult↗
PubMed2001

[IgE antibody determination].

Bronchial asthma is assumed to be the representative allergic disorder, and allergic reactions play an important role in its pathogenesis in about 70% of asthmatic subjects. It is essential to identity and remove relevant causative allergen(s) from therapeutic point of view to reduce symptoms and to improve quality of life, in these patients. For this purpose, skin tests, in vitro IgE antibody measurements including CAP RAST, multiple antigen simultaneous test (MAST), AlaSTAT, LUMIWARD and quidel allergy screen (QAS), as well as histamine release test (HRT) are currently employed in Japan. This review summarizes their recent progress.

Asthma↗