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PubMed1994

Detection of antibodies against corrosion products in patients after Co-Cr total joint replacements.

Sensitivity to nickel, cobalt, and chromium is common among the general population. The identification of these sensitivities is generally by the detection of cell-mediated immunity. Detection of humoral immunity to these metals has rarely been undertaken because suitable assays are not available. To further our knowledge about the systemic humoral immune system response to weak hapten-syngeneic or allogeneic protein conjugates (corrosion and wear products of metallic orthopedic devices), a sensitive enzyme-linked immunosorbent assay (ELISA) method for testing for antibody (humoral immunity) to metals was developed. Microtiter plates were coated with human serum albumin (HSA) or glutathione (GSH) and then conjugated with metal ions. Plates coated with HSA or GSH and without metal ions served as background controls. An indirect ELISA method was used to detect antibody binding. Patients bearing cobalt-chromium alloy devices were considered to be the most likely candidates as sources of antibody to metal and were used to document the usefulness of the test. Specificity of the test was documented by inhibition studies with these metal ions in the ELISA assay. The serum samples of 10 patients were screened for the presence of Cr-, Co-, or Ni-specific antibody at various periods up to 5.5 years after implantation of F-75 cobalt alloy total joint replacements. All patients had implants that were functioning well. The pre- and postimplantation humoral immune profiles of patients were determined and compared with each preimplantation control and with a pooled normal serum sample. This study presents evidence that metal-protein complex-specific antibodies can be detected. The clinical implications remain to be determined.

Antibodies↗
PubMed1982

Spontaneous diabetes in BB rats: evidence for a T cell dependent immune response defect.

Approximately 50% of BB rats develop insulinopenic hyperglycaemia and ketosis spontaneously in association with insulitis. Amelioration of the syndrome by immunosuppression suggests a cell mediated immune pathogenesis. Analysis of the cell-mediated immune profile of overtly diabetic and normoglycaemic diabetes prone BB rats indicates that they are lymphocytopenic relative to non-diabetes prone BB rats and that the T cell pool is particularly affected. Furthermore, lymphocytes from diabetic and diabetes prone BB rats, while producing normal responses to the T cell mitogen concanavalin A, do not respond when mixed in vitro with major histocompatibility complex incompatible lymphocytes. This anergy is not restored either by enriching the responding cell population for T cells or by adding exogenous T cell growth promoting factor. Thus BB rats have a numerical and regulatory deficit of their T cells which could be related to their propensity for diabetes.

Animals↗
PubMed1978

Meningoencephalitis syndrome following influenza vaccination.

Immunological reactions to non-virus substances of vaccines may be of considerable significance to the pathogenesis of neurological complications after anti-influenza vaccination. A 60 year old female patient with a known allergic diathesis developed a meningoencephalitis syndrome a few hours after vaccination. The case history as well as the clinical course suggested an immunopathogenetic mechanism. We therefore analyzed the immune profile. Intracutaneous testing with chicken meat and chicken egg protein lead to a striking local anaphylactic reaction which is discussed in causal relation to the postvaccination complication.

Allergens↗
PubMed1994

Subcutaneous granuloma annulare: four cases and review of the literature.

Subcutaneous granuloma annulare (SGA) produces benign nodules in otherwise healthy children. The histology of the lesions may be indistinguishable from rheumatoid nodules. However, in children the lesion of SGA is not accompanied by connective-tissue disease. We report 4 patients with SGA. There were three girls and one boy ranging in age from 4 to 15 years. All the children presented with a solitary lesion on the lower limb. A cutaneous lesion was also present in case 4. In only one patient (case 4) was there a history of trauma. There was no relevant past medical history. Routine laboratory tests were normal (including ESR and auto-immune profile). A computed tomography (CT) scan with intravenous contrast was performed in all patients. The CT features were those of soft tissue masses of variable attenuation and enhancement with inconsistent infiltration into surrounding fat. There appear to be no specific CT features which distinguish this benign lesion from a more sinister one. Excisional biopsy was performed in all cases. In children, SGA should be included in the differential diagnosis of soft-tissue masses, particularly in the lower extremity.

Adolescent↗
PubMed1984

Further studies on immunological parameters in gestational trophoblastic neoplasia.

The total blood lymphocyte counts, T-cell counts, B-cell counts, percentage of T cells bearing Fc receptors for IgG (TG), lymphocyte responses to phytohaemagglutinin and concanavalin A and serum IgA levels were measured in 15 patients with hydatidiform mole, 32 patients with malignant trophoblastic disease, 30 pregnant controls, and 34 normal non-pregnant controls. The mean percentage of TG was similar in all four groups but the mean absolute number of TG in patients with malignant trophoblastic disease was significantly lower than that in normal non-pregnant controls, due to the lower mean lymphocyte count and T-cell count in the former group. An immune profile score based on the T-cell count, B-cell count, lymphocyte response to mitogens, and serum IgA level was useful in predicting the subsequent development of malignant trophoblastic disease in patients with hydatidiform mole but was not helpful in predicting resistance to chemotherapy in malignant trophoblastic disease.

Adolescent↗
PubMedDate not supplied

Arthropathy associated with Brucella abortus strain 19 vaccination in cattle. I. Examination of field cases.

Thirty cows presenting with lameness and persistent serological reactions to Brucella abortus had chronic granulomatous arthropathy of the femorotibial and occasionally other joints. Attempts to culture Brucella or other pathogens gave negative results but organisms of Brucella morphology were seen in fluorescent antibody-stained cryostat sections of synovial tissue. The synovial fluids contained high titres of antibodies to B. abortus and Yersinia enterocolitica O:9 and had elevated total protein and immunoglobulin concentrations showing an oligoclonal electrophoretic profile. Immune complexes and rheumatoid factor were detected in some of the fluids.

Animals↗
PubMed1980

Immunological parameters in gestational trophoblastic neoplasia.

Immunological function were studied in 22 patients with hydatidiform mole and 29 patients with malignant trophoblastic disease before and after treatment; normal pregnant and post-pregnant women served as controls. The only significant abnormality in hydatidiform mole was a low granulocyte chemotaxis before evacuation. In malignant trophoblastic disease the total lymphocyte counts, T-cell counts. B-cell counts, lymphocyte responses to mitogens and serum IgA levels were significantly lower than in normal women 6 wk after pregnancy. In those who responded to chemotherapy, these indices rose to the levels of post-pregnancy controls. An 'immune profile score' based on these indices was found to be a useful prognostic index. All patients with hydatidiform mole who had a score of 7 or less developed malignant trophoblastic disease, while the two patients with malignant trophoblastic disease who died had the lowest scores of the series.

Adolescent↗
PubMed2026

Genomic and transcriptomic features of HBV integration in treatment-naïve, HBeAg-positive children with chronic HBV infection.

BACKGROUND: Hepatitis B virus (HBV) integration represents a major obstacle to curing HBV; however, the landscape of HBV integration and local immune response to transcriptionally active viral integration in children with chronic HBV infection remain unclear. Herein, we aimed to elucidate this landscape in this population. METHODS: Genomic analyses using a probe-based capture strategy were performed on 18 children and 28 adults with chronic HBV infection. Spatial transcriptomics (ST) was performed on 12 children from our cohort and 3 adults from a public database. FINDINGS: All patients were hepatitis B e antigen (HBeAg)-positive and treatment-naïve. Genomically, children exhibited significantly lower clonal expansion level of HBV-integrated hepatocytes than adults, despite comparable unique breakpoint counts. After adjusting for confounding variables, age was identified as an independent risk factor for total frequency of unique integration breakpoints (b = 3.22, P = 0.005). Spatially, ST revealed that spots with transcriptionally active viral integration exhibited a sparse distribution and accounted for a low proportion of all spots in children. Notably, at these spots, children showed reduced adaptive immune cells (e.g., CD8+ T cells) but increased innate components (myeloid cells, Kupffer cells, activated dendritic cells) and APC co-stimulation, whereas adults exhibited a uniform reduction of immune cell populations. INTERPRETATION: Compared with adults, children exhibit lower clonal expansion of HBV-integrated hepatocytes and distinct immune profiles in response to transcriptionally active viral integration, offering new insights into their differing clinical course. FUNDING: Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education).

Humans↗
PubMed2005

Evolution of self-reactive IgG antibody repertoires in patients with relapsing-remitting multiple sclerosis.

We have previously demonstrated a distortion of self-reactive IgG antibody repertoires in patients with multiple sclerosis (MS) compared to controls, by immunoblotting assays, using human brain homogenates. The analysis of the immune profiles against human brain antigens allowed us to distinguish MS patients, and to associate a particular pattern of reactivity for each clinical form of MS. The aim of the present study was to evaluate the evolution of such patterns in patients with relapsing-remitting MS (RRMS). In a first step, we confirmed, by western blotting using human brains as source of antigens, the existence of specific repertoires of IgG reactivity in whole serum collected from healthy subjects (n = 32) and from untreated patients with RRMS (n = 56). In a second step, the evaluation of patterns was performed at baseline and 1 year later in untreated RRMS patients (n = 15), and in RRMS patients treated with IFN-beta (n = 41). In both groups, little change in IgG reactivity in whole serum was found. However, a higher degree of stability was noted in treated versus untreated patients (P < 0.01). Our results have showed a specific and relatively stable pattern of reactivity for each RRMS individual tested against brain antigens even after a 1-year treatment prevailing in treated patients suggesting that IFN-beta could stabilize IgG antibody repertoires.

Adult↗
PubMed2026

Tonsillar expression quantitative trait loci verify and expand genetic contributors to childhood atopic diseases.

BACKGROUND: The spectrum of causal variants, mechanisms, and immunologic gene networks that influence pediatric atopic traits is not completely understood. Human genetic variation associated with transcript abundance (expression quantitative trait loci [eQTLs]) can help to advance our understanding, yet prior work has focused on profiling immune cell populations collected from peripheral blood primarily in adult populations, leaving tissue-resident lymphocytes collected from children uncharacterized. OBJECTIVE: We sought to characterize gene expression of 4 populations of tonsil-derived immune cell types collected from pediatric patients. METHODS: We collected naive B, germinal center B, naive T, and T follicular helper cells from the discarded tonsils of 103 children across development (age range 1-19). Following genotyping and RNA sequencing of samples, we performed differential expression and eQTL analysis, then statistically linked eQTL signals to relevant atopic traits via colocalization. RESULTS: We found differentially expressed genes across cell types and identified 13,393 expression genes (eGenes) (1,793 eGenes not previously reported in similar datasets) influenced by 27,603 eQTLs (5,199 eQTLs not previously reported). We linked eQTLs to associations identified in pediatric and adult asthma and atopy traits, nominating 78 eGenes including TRAF3, ZBTB10, and JAZF1 in disease-relevant cell types. CONCLUSIONS: Our freely available resource exemplifies the importance of discovery in native tissues and across human development.

Expression quantitative trait locus↗
PubMed2006

A depressed peripheral cellular immune response is related to symptomatic neurocysticercosis.

Human neurocysticercosis can cause mild or severe neurological symptoms or be completely asymptomatic. This heterogeneity may depend on host factors such as gender, age and immune-inflammatory response. The present study describes the specific peripheral immune response related to the different forms of neurocysticercosis in the adult population of both sexes. Asymptomatic cases (n = 26) mainly presented single calcified cysticerci in brain parenchyma or in the subarachnoid space of the sulci with a predominantly TH2 response (IL-4, IL-5, IL-13), high levels of IL-12 in supernatants of specifically stimulated peripheral blood mononuclear cells, and low plasma levels of all specific IgG subclasses. Symptomatic patients (n = 26) constituted a heterogeneous group, and had single or multiple cysticerci in vesicular, colloidal, calcified or mixed stages. This group showed parasites located in the subarachnoid space of the base and/or in the sulci, in the ventricular cavities, in parenchyma or in mixed locations. Symptomatic patients showed a depressed specific cellular immune response and increased levels of all specific IgG subclasses. This evidence supports the existence of two clear different immune profiles according to neurocysticercosis that is asymptomatic or symptomatic.

Adult↗
PubMed2004

Dendritic cell sarcoma of the oral cavity.

Sarcomas derived from immune accessory cells are uncommon malignancies, most of them occurring in lymph nodes while extra nodal sites are very rarely affected. Based on the immune profile, the cells that give origin to these neoplasms are currently divided in: follicular dendritic cell (FDC), interdigitating dendritic cell (IDC), indeterminate cell and Langerhans cell. A case of a dendritic cell sarcoma arising in the alveolar ridge mucosa in a 50-year-old female is reported here. The lesion presented as a nodular mass without defined borders and covered by reddish mucosa. Histologically, the tumour was composed of spindle-shaped cells with large nuclei and abundant cytoplasm, arranged in variable patterns as storiform and whorled and revealing interspersed lymphocytes. No capsule could be seen and the neoplasm extended up to the lining epithelium. Immunohistochemically, the spindle cells were positive for vimentin, S-100 protein, CD1a, factor XIIIa and focally to smooth-muscle actin, but were negative for CD21, CD35, CD23 and caldesmon--all markers of follicular dendritic cells. In conclusion, the present case has morphologic pattern of dendritic cell sarcoma and the immunophenotype is compatible with IDC cells or with intermediate dendritic cells and demonstrates the overlap of features among these entities.

Alveolar Process↗
PubMed2004

Immunological monitoring of posttransplant allograft sensitization following living related donor renal transplantation.

A better understanding of the immunobiological processes and predictors of graft rejection holds promise for development of new therapeutic strategies and also for individualization of immunosuppression. The objective of this study was to analyze the clinical relevance of immune parameters, such as recipient sensitization status, donor-specific antibodies, and anti-HLA antibodies, which are major predictors of graft outcome following renal transplantation. Sera from 264 renal recipients at different posttransplant period were included for detection of anti-donor antibodies (by flowcytometry); anti-HLA, antibody (by ELISA), and panel-reactive antibodies (PRA) by complement-dependent cytotoxicity (CDC) methods. Graft survival was analyzed in relation to posttransplant PRA at 2 years follow-up time: overall survival was significantly compromised in the highly sensitized group (group III) compared to the other two groups (overall chi2 = 24.20, P = 5.5 x 10(-06)). Flow cytometric cross-matches revealed the presence of anti-donor class I antibodies (T+) in 39 patients who had a poor graft survival of 51% compared with 85% survival in 225 antibody-negative patients. (chi2 = 22.260, P = 2.381 x 10(-.06)). Further analysis was performed based on the presence or absence of FCXM and ELISA-detected antibodies. Recipients belonging to group I (ELISA+/FCXM+) showed significantly lower graft survival (43%) compared with that observed in group II, which were essentially nonsensitized individuals (90%; P = 3.1 x 10(-08)). The graft survival in the ELISA-/FCXM+ group was 63%, which was significantly lower than that in group II (P = 5.14 x 10(-03)). Group IV (ELISA+/FCXM-) including 38 (14%) serum samples with nondonor but HLA-specific antibodies was associated with significantly poorer graft survival (63%) compared with group II (P = 6.6 x 10(-05)). Our data also show that while FCXM is the most sensitive test to detect donor-specific antibodies, the ELISA method offers the additional advantage of detecting anti-HLA class-I antibodies, which are detrimental for renal graft survival. Thus the use of multiple parameters to assess recipient immune profile can predict graft outcome more accurately thus helping the individualization and optimization of immunosuppression.

Follow-Up Studies↗
PubMed2004

Protective and disease-enhancing immune responses induced by recombinant modified vaccinia Ankara (MVA) expressing respiratory syncytial virus proteins.

Modified vaccinia Ankara (MVA) recombinants expressing single or multiple RSV surface proteins (F or G) are promising potential vaccines. We studied humoral and cellular responses induced by MVA-F and MVA-G in mice, comparing them to a formalin inactivated RSV preparation (FI-RSV) known to increase disease severity. MVA-F or MVA-G vaccination enhanced weight loss during RSV challenge, but did not show the lung eosinophilia seen after FI-RSV vaccination. FI-RSV induced a stronger total RSV IgG response than the MVA recombinants, but very little IgG2a. MVA recombinants induced cytokine responses biased towards IFNgamma and IL-12, while FI-RSV induced strong IL-4/5 responses in the lungs during RSV challenge. Thus, MVA vaccines induce a favourable immune profile in RSV disease but retain the potential to enhance disease.

Animals↗
PubMed1993

Analysis of peripheral blood lymphocyte cell surface density of functional and activation associated markers in young and old hemodialysis patients.

Aging has been associated with specific shifts in various peripheral blood immune competent cell subsets. As part of pre-transplant immune profile evaluation possible parallel age-related changes in mean T-cell surface density of several cluster differentiation and activation linked antigens were into 2 groups: group 1-114 patients 40 years old or younger and group 2-36 patients 55 years old or older. Peripheral blood CD3+, DR+, CD3+DR+, CD4+, CD4+DR+, CD8+, CD8+DR+, CD56+, CD8+CD56+, CD3+IL-2-R+ and CD3+TR+ (interleukin-2 and transferrin receptors bearing CD3+ cells respectively), all mononuclear cells expressing IL-2-R and TR, and CD4+CD45+ cell subsets were analyzed and enumerated by 2-color flow cytometry. Subset relative levels as well as absolute counts were recorded. Cell surface density computation was performed using a computerized mathematical model based on fluorescence intensity vector analysis and cell size score determination based on light scatter pattern from raw data obtained by flow cytometry studies. Younger age was significantly associated with higher absolute cell count of CD3+ (p < 0.001), DR+ (p < 0.05), CD4+ (p < 0.01), CD8+ (p < 0.005), CD3+IL-2-R+ (p < 0.05), CD3+TR+ (p < 0.03) and IL-2-R+ (p < 0.05). Older patients had a slightly higher mean absolute count of CD4+CD45+ subset (p not significant) and significantly higher mean count for CD8+CD56+ cell subset (p < 0.001). When cell subset levels were compared between the 2 groups as the relative fraction of cells expressing a given marker out of all mononuclear cells gated out by flow cytometry, younger age was significantly associated with higher levels of CD3+ (p < 0.005), CD8+ (p < 0.001), CD4+DR+ (p < 0.004), CD3-TR+ (p < 0.05) and CD8+IL-2-R+ (p < 0.05). In contrast, slightly higher subset levels of CD56+ (p not significant), and significantly elevated levels of CD8+CD56+ (p < 0.0019) and CD4+CD45+ (p < 0.004) were observed in the older patients. Cell surface density analysis showed that younger patients had higher mean density per cell of CD3 (p < 0.05), CD8 (p < 0.001), IL-2-R on CD3+ cells (p < 0.05) and TR on CD3+ cells (p < 0.05). Mean cell surface density of CD56 on all CD56+ cells as well as on CD8+ cells was higher in older individuals (p < 0.001 and p < 0.003, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1999

Immunostimulatory DNA and applications to allergic disease.

The vertebrate immune system reacts to certain sequences of DNA with a strong T(H)1-inducing innate response. These sequences, termed immunostimulatory DNA sequences, are not fully defined but generally consist of a central nonmethylated CG dinucleotide, flanked by less highly conserved sequences (hence the alternate name CpG motifs). These sequences seem to be rare in vertebrates but relatively common in many lower organisms, including bacteria and viruses. It is likely that these sequences represent a danger signal to the immune system; a powerful T(H)1 response is induced against colocalized foreign antigen. This can be used to modify an allergic response away from a pathogenic T(H)2-dominated immune profile toward a nonpathogenic and even protective T(H)1 profile.

Adjuvants, Immunologic↗
PubMed2001

An analysis of cytokine status in the serum and effusions of patients with tuberculous and lung cancer.

The present study was designed to ascertain whether or not the pleural effusion and serum cytokine levels (granulocyte-macrophage colony-stimulating factor [GM-CSF], interleukin-10 [IL-10], and interferon-gamma [IFN gamma]) in lung cancer patients differ from tuberculous (TB) pleural effusion, in which a strong cellular immune reaction is found; and, whether cytokine levels are a prognostic factor in lung cancer patients with malignant effusion. A total of 202 lung cancer patients with malignant pleural effusion and 26 patients with TB pleural effusion were studied consecutively between 1995 and 1998. Serum and effusion cytokine levels were analyzed with ELISA assays. The results showed that pleural effusion GM-CSF and IL-10 levels were significantly higher than serum levels in both cancer and TB patients. Pleural effusion IFN gamma levels were significantly higher than serum levels in TB patients. IFN gamma levels in both pleural effusion and serum were significantly higher in TB patients than in those with cancer. No significant difference was found, between TB and cancer patients, in the serum or pleural effusion levels of either IL-10 or GM-CSF. The ratio of pleural effusion IFN gamma to serum IFN gamma, effusion IFN gamma to effusion IL-10, and effusion IL-10 to serum IL-10, were all significantly higher in TB than in cancer patients, suggesting a higher cellular activity and T-helper 1 (Th1) reaction in TB pleural effusion than in malignant effusions, which were predominantly Th2 type. Survival analysis showed no significant difference in lung cancer patients with different levels of these cytokines. It was concluded that lung cancer patients with malignant pleural effusion had poorer immune profiles than those with TB pleurisy, both locally and systemically; and the cytokine profiles were not prognostic factors for lung cancer patients with malignant pleural effusion.

Aged↗
PubMed1990

Blood testosterone level: a season-dependent factor regulating immune reactivity in lizards.

An attempt to study the interaction between testosterone (Ts) and the immune system of the lizard Chalcides ocellatus led to three major findings: 1) Endogenous serum Ts levels in both males and females peak in spring and are minimal during summer; 2) Injection of Ts in either male or female lizards induces significant depletion of lymphoid elements, reduction in serum antibody titers to rat erythrocytes and increase in skin allograft survival; 3) A distinct inverse correlation between endogenous serum Ts levels and lizard immunocompetence is observed from March to September. The data obtained strongly suggested that concentration of circulating Ts is a season-related factor that is critical in defining the immune profile of lizards.

Animals↗