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1.
Clin Exp Immunol ; 192(3): 284-291, 2018 06.
Article in English | MEDLINE | ID: mdl-29878323

ABSTRACT

This is the second report of the United Kingdom Primary Immunodeficiency (UKPID) registry. The registry will be a decade old in 2018 and, as of August 2017, had recruited 4758 patients encompassing 97% of immunology centres within the United Kingdom. This represents a doubling of recruitment into the registry since we reported on 2229 patients included in our first report of 2013. Minimum PID prevalence in the United Kingdom is currently 5·90/100 000 and an average incidence of PID between 1980 and 2000 of 7·6 cases per 100 000 UK live births. Data are presented on the frequency of diseases recorded, disease prevalence, diagnostic delay and treatment modality, including haematopoietic stem cell transplantation (HSCT) and gene therapy. The registry provides valuable information to clinicians, researchers, service commissioners and industry alike on PID within the United Kingdom, which may not otherwise be available without the existence of a well-established registry.


Subject(s)
Epidemiological Monitoring , Immunologic Deficiency Syndromes/epidemiology , Registries/statistics & numerical data , Female , Humans , Immunologic Deficiency Syndromes/immunology , Immunologic Deficiency Syndromes/therapy , Male , United Kingdom/epidemiology
2.
Epidemiol Infect ; 145(12): 2424-2435, 2017 09.
Article in English | MEDLINE | ID: mdl-28689517

ABSTRACT

The aim of this study was to ascertain farmers' knowledge of the risk of spread of infection from animals to humans, and their transmission prevention practices. This was a survey of farmers who submitted material to Ireland's Regional Veterinary Laboratories in 2015. There was an 84% response rate (1044 farmers). Ninety per cent of farmers were not aware that infection can be acquired from apparently healthy animals. Over half were not aware that disease could be contracted from sick poultry or pets. Conversely, the knowledge of the risk to pregnant women of infection from birthing animals was high (88%). Four-fifths of farmers sourced drinking water from a private well, and of these, 62% tested their water less frequently than once a year. Of dairy farmers, 39% drank unpasteurised milk once a week or more frequently. Veterinarians were the most commonly cited information source for diseases on farms. The survey findings indicate that the level of farmers' knowledge and awareness of the spread of infection from animals to humans is a concern. Further education of the farming community is needed to increase awareness of both the potential biohazards present on farms and the practical measures that can be taken to mitigate the risk of zoonoses.


Subject(s)
Farmers/psychology , Health Knowledge, Attitudes, Practice , Zoonoses/prevention & control , Zoonoses/transmission , Adolescent , Adult , Aged , Aged, 80 and over , Animals , Female , Humans , Ireland , Male , Middle Aged , Risk Assessment , Young Adult , Zoonoses/psychology
3.
Clin Exp Immunol ; 181(1): 110-7, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25737039

ABSTRACT

Antiretroviral therapy (ART) only partially restores HIV-induced alterations in lymphocyte populations. We assessed B and T cell phenotypes in a cohort of children from a single centre in the United Kingdom with perinatally acquired HIV compared to healthy controls. The majority of HIV infected children (44 of 56) were on fully suppressive combination ART. Children with perinatally acquired HIV had significantly lower memory B and CD4(+) CD45RO(+) CXCR5(+) [follicular T helper cell (Tfh)-like] T cell percentages. Detectable viraemia was associated with higher CD21(-) (activated and exhausted/tissue-like memory) B cells. A greater proportion of life spent on suppressive ART was associated with higher memory B cell percentages. These results suggest that early and sustained suppressive ART may preserve B and T cell phenotypes in perinatally acquired HIV and limit deficits in humoral immunity. A lower proportion of circulating Tfh-like cells in HIV infected children appears to be independent of HIV treatment history and ongoing HIV viraemia and warrants further investigation.


Subject(s)
B-Lymphocyte Subsets/immunology , HIV Infections/immunology , Immunologic Memory/immunology , Receptors, CXCR5/metabolism , T-Lymphocytes, Helper-Inducer/immunology , Adolescent , Anti-Retroviral Agents/therapeutic use , B-Lymphocyte Subsets/virology , Child , Child, Preschool , Female , HIV Infections/drug therapy , Humans , Infant , Male , Receptors, Complement 3d/immunology , T-Lymphocytes, Helper-Inducer/virology
4.
Vet J ; 199(3): 370-5, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24507882

ABSTRACT

To investigate the usefulness of culture for the confirmation of brucellosis in cattle, a comparison of culture and serology was undertaken on 248 animals in four dairy herds where the disease was active. Paired supramammary (SM), retropharyngeal (RP), and internal iliac (IL) lymph nodes were cultured, and five serological tests were deployed: the microserum agglutination test (MSAT), complement fixation test (CFT), the indirect (iELISA) and competitive ELISA, and the fluorescence polarisation assay (FPA). Brucella abortus was isolated from 86.8% of animals on combined culture of all three lymph nodes. Individually, the highest isolation rate was from the RP (90.5% of culture positives). Of culture positive animals, 13.7% and 6.2% were positive from the RP and SM alone, respectively. Approximately half of the positive cultures yielded <10 colonies/culture plate. Although 80.9% of animals were positive in at least one serological test, only 45.2% were positive in all five. For culture-positive animals, the MSAT was the most sensitive test (71.8%). Of the culture-negative animals 67.7% were positive in at least one test, while 12.9% were positive in all five. Titres were higher in animals culture-positive from the SM, and there was a direct correlation between higher titres and higher colony counts in SM cultures. Only 8.9% of animals were both culture-negative and seropositive (in at least one test), while 16.5% were culture-positive and seronegative in all five tests. The results highlight and validate the sensitivity of bacteriological culture in confirming a diagnosis of bovine brucellosis. While the MSAT and FPA were the most sensitive serological tests, a significant percentage of infected animals were undetectable using these standard serological assays.


Subject(s)
Brucella abortus/isolation & purification , Brucellosis/veterinary , Cattle Diseases/diagnosis , Colony Count, Microbial/veterinary , Serologic Tests/veterinary , Animals , Brucellosis/diagnosis , Brucellosis/microbiology , Cattle , Cattle Diseases/microbiology , Colony Count, Microbial/methods , Female , Ireland , Sensitivity and Specificity , Serologic Tests/methods
5.
Clin Exp Immunol ; 170(2): 212-21, 2012 Nov.
Article in English | MEDLINE | ID: mdl-23039892

ABSTRACT

Dendritic cells (DC) in HIV-1-infected individuals are decreased and their dysfunction has been implicated in HIV-1 immunopathogenesis. The mechanism of their dysfunction remains unclear, thus we analysed the expression of membrane molecules associated with immune regulation and DC activation in myeloid (mDC) and plasmacytoid DC (pDC) in therapy-naive and highly active anti-retroviral therapy (HAART)-treated HIV-1(+) patients. DC from healthy controls, untreated HIV-1(+) and HAART-treated patients were assessed by flow cytometry for expression of: anergy and apoptosis inducing molecules [programmed death (PD)-1 and its ligands PD-L1 and PD-L2], inhibitory and regulatory T cell-inducing molecules [immunoglobulin-like transcript (ILT)-3 and ILT-4], interferon (IFN)-α inhibitory receptor (ILT-7) and co-stimulatory molecules (CD80, CD83, and CD86). pDC from untreated HIV-1(+) patients expressed significantly lower levels of ILT-7 compared to healthy controls, while HAART-treated patients showed normal expression. pDC were also found to express moderately higher levels of PD-L1 and ILT-3 and lower levels of PD-L2 receptors in untreated patients compared to controls and HAART-treated patients. No significant changes were observed in mDC. There were no associations between the percentages and levels of expression of these molecules by pDC and viral load or CD4 T cell count. In conclusion, pDC but not mDC from HIV-1(+) patients with active viraemia display higher levels of apoptosis and T regulatory-inducing molecules and may be predisposed to chronically produce IFN-α through down-regulation of ILT-7. HAART restored normal expression levels of these receptors.


Subject(s)
Dendritic Cells/immunology , HIV Infections/immunology , Myeloid Cells/immunology , Adult , Antigens, CD/immunology , Antigens, CD/metabolism , Antiretroviral Therapy, Highly Active/methods , B7-H1 Antigen/immunology , B7-H1 Antigen/metabolism , Cohort Studies , Dendritic Cells/metabolism , Female , HIV Infections/drug therapy , HIV Infections/metabolism , HIV Infections/pathology , HIV-1/immunology , Humans , Immunophenotyping , Male , Membrane Glycoproteins/immunology , Membrane Glycoproteins/metabolism , Middle Aged , Myeloid Cells/metabolism , Programmed Cell Death 1 Receptor/immunology , Programmed Cell Death 1 Receptor/metabolism , Receptors, Cell Surface/immunology , Receptors, Cell Surface/metabolism , Receptors, Immunologic/immunology , Receptors, Immunologic/metabolism , Viremia/immunology , Viremia/metabolism , Young Adult
6.
J Perinatol ; 32(5): 387-9, 2012 May.
Article in English | MEDLINE | ID: mdl-22538377

ABSTRACT

Common variable immunodeficiency (CVID) is a rare condition that affects women of childbearing age with important implications in pregnancy. It is characterised by low immunoglobulins (Igs), poor antibody response and a susceptibility to recurrent infections. The cornerstone of management of CVID is Ig replacement. As the transfer of IgG across the placenta in the third trimester of pregnancy is necessary for protection of the infant in the first months of life, failure to recognise this condition and treat it appropriately can have adverse consequences for the neonate, as well as the mother. Here we describe the complex perinatal medical management of a 34-year-old woman who was diagnosed with CVID in the 26th week of pregnancy.


Subject(s)
Cesarean Section , Common Variable Immunodeficiency/diagnosis , Common Variable Immunodeficiency/therapy , Postnatal Care/methods , Pregnancy Complications, Hematologic/diagnosis , Combined Modality Therapy , Disease Management , Drug Therapy, Combination , Female , Follow-Up Studies , Gestational Age , Humans , Infant, Newborn , Parity , Pregnancy , Pregnancy Complications, Hematologic/therapy , Rare Diseases
8.
Eur Respir J ; 34(6): 1376-82, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19541722

ABSTRACT

Multiplex protein technology has the potential to identify biomarkers for the differentiation, classification and improved understanding of the pathogenesis of interstitial lung disease. The aim of this study was to determine whether a 30-inflammatory biomarker panel could discriminate between healthy controls, sarcoidosis and systemic sclerosis (SSc) patients independently of other clinical indicators. We also evaluated whether a panel of biomarkers could differentiate between the presence or absence of lung fibrosis in SSc patients. We measured 30 circulating biomarkers in 20 SSc patients, 21 sarcoidosis patients and 20 healthy controls using Luminex bead technology and used Fisher's discriminant function analysis to establish the groups of classification mediators. There were significant differences in median concentration measurements between study groups for 20 of the mediators but with considerable range overlap between the groups, limiting group differentiation by single analyte measurements. However, a 17-analyte biomarker model correctly classified 90% of study individuals to their respective group and another 14-biomarker panel correctly identified the presence of lung fibrosis in SSc patients. These findings, if they are corroborated by independent studies in other centres, have potential for clinical application and may generate novel insights into the modulation of immune profiles during disease evolution.


Subject(s)
Biomarkers/metabolism , Pulmonary Medicine/methods , Sarcoidosis/blood , Scleroderma, Systemic/blood , Adolescent , Adult , Aged , Case-Control Studies , Female , Fibrosis/blood , Humans , Immune System , Intercellular Signaling Peptides and Proteins/metabolism , Male , Middle Aged
9.
Clin Exp Allergy ; 38(7): 1132-9, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18564333

ABSTRACT

OBJECTIVE: We aim to find what is the relationship between B cell antibody responses and specific T cell help in the specific cases of allergy and tolerance to peanuts. BACKGROUND: B cell antibody responses to foreign proteins usually depend upon antigen-specific T cell help. However, specific antibody levels can sometimes be maintained lifelong after infections or vaccination. METHODS: We measured peanut-specific proliferation and antibody levels in peanut-allergic and non-allergic children using tritiated thymidine incorporation and UniCAP, respectively. We also investigated the corresponding tetanus toxoid specific responses in both groups. RESULTS: We found that tetanus-specific IgG did not correlate with lymphocyte proliferation (Spearman rank correlation coefficient r'=0.08, P=0.74) nor with tetanus-specific cytokine production (IFN-gamma: r'=0.198, P=0.285; TNF-alpha: r'=0.274, P=0.146; IL-4: r'=-0.007, P=0.96; P=0.221; IL-13: r'=0.363, P=0.056). Conversely, in peanut-allergic donors, peanut-specific IgE (average 21 kU/L, median 2.27 kU/L, range 0.34-100 kU/L) but not peanut-specific IgG was positively correlated with proliferation (r'=0.751, P=0.003). In these donors, specific IgE was positively correlated with peanut-specific Th2 cytokines production: r'=0.635, P=0.02 for IL-4 and r'=0.641, P=0.025 for IL-13 and negatively correlated with Th1 cytokines (r'=-0.71, P=0.007 for IFN-gamma and r'=-0.746, P=0.005 for TNF-alpha, respectively). However, peanut-specific IgE was not correlated with T cell proliferation or cytokine production in non-allergic individuals. In conclusion, in allergic individuals, B and T cell responses to peanut antigens are correlated whereas normal immune responses B and T cell responses are uncoupled. CONCLUSION: Our results support the view that B cell responses to allergens but not those to non-allergenic proteins are correlated with specific T cell responses and therefore specific immunotherapy targeting of such T cells would inhibit allergen-specific B cells.


Subject(s)
Arachis/immunology , B-Lymphocytes/immunology , Cytokines/metabolism , Immunoglobulin E/blood , Peanut Hypersensitivity/immunology , T-Lymphocytes/immunology , Tetanus Toxoid/immunology , B-Lymphocytes/metabolism , Cell Proliferation , Child , Cytokines/immunology , Humans , Lymphocyte Activation , T-Lymphocytes/metabolism
10.
HIV Med ; 9(2): 118-25, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18257774

ABSTRACT

OBJECTIVE: The aim of the study was to determine whether the expression of CD38 on CD8 T cells can identify patients with virological failure on antiretroviral therapy (ART). DESIGN: This was a cross-sectional study of patients attending a single HIV clinic in London. METHODS: The expression of CD38 on CD8 T cells was assessed using a biologically calibrated flow cytometry protocol. Patients were characterized by lymphocyte subset and viral load measurements. Characteristics including historical CD4 T cell counts, therapeutic history, co-infections and demographics were obtained from medical records. RESULTS: Elevated levels of CD8 CD38(high) T cells were found in HIV-1-infected patients who failed to suppress viral replication with ART; however, this parameter lacked sufficient sensitivity and specificity to replace viral load testing in assessing the efficacy of ART. Increased levels of CD8 CD38(high) cells were associated with reduced CD4 T cell counts in HIV-1-infected patients on ART after correcting for known determinants of CD4 T-cell recovery. CONCLUSIONS: The expression of CD38 on CD8 T cells lacks sufficient sensitivity and specificity to be used as a surrogate marker for viral load to monitor HIV-1 infection. T-cell activation is associated with reduced CD4 T-cell reconstitution in patients receiving ART.


Subject(s)
ADP-ribosyl Cyclase 1/metabolism , Antiretroviral Therapy, Highly Active , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , HIV Infections/immunology , HIV-1 , Adult , Cross-Sectional Studies , Female , HIV Infections/drug therapy , HIV Infections/virology , Humans , London , Male , Treatment Failure , Virus Replication/drug effects , Virus Replication/immunology
11.
Clin Exp Immunol ; 154(3): 399-405, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19222502

ABSTRACT

Both virus-associated haemophagocytic syndrome (HPS) and human immunodeficiency virus-associated multi-centric Castleman's disease (HIV-MCD) induced by human herpesvirus-8 (HHV-8) are extremely rare. We therefore wished to investigate their occurrence together, and establish the degree of cytokine activation present. From a prospective cohort of individuals with HIV-MCD, we investigated the incidence and outcomes of HPS and measured 15 inflammatory cytokines and the plasma HHV-8 viral loads before and during follow-up. Of 44 patients with HIV-MCD with an incidence of 4.3/10,000 patient years, four individuals (9%) were diagnosed with HPS. All are in remission (range 6-28 months) following splenectomy, etoposide and rituximab-based therapy. Plasma HHV-8 levels were raised markedly at presentation (median 3,840,000 copies/ml). Histological samples from spleen, splenic hilar lymph nodes and bone marrow demonstrated increased phagocytosis by histiocytes and presence of HHV-8-infected plasmablasts outside the follicles. Surprisingly, many known inflammatory plasma cytokines were not elevated, although interleukin (IL)-8 and interferon-gamma were increased in all cases and IL-6 levels were raised in three of four patients. HPS in the setting of HIV-MCD is common and treatment can be successful provided the diagnosis is made appropriately. Systemic activation of cytokines was limited, suggesting that immunosuppressive therapy with steroids is not indicated in HHV-8-driven HPS.


Subject(s)
Castleman Disease/virology , Cytokines/metabolism , HIV Infections/complications , Lymphohistiocytosis, Hemophagocytic/complications , Adult , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Murine-Derived , Antineoplastic Agents, Phytogenic/therapeutic use , Antiretroviral Therapy, Highly Active , Combined Modality Therapy , Drug Therapy, Combination , Etoposide/therapeutic use , HIV Infections/drug therapy , Herpesvirus 8, Human , Humans , Immunologic Factors/therapeutic use , Lymphohistiocytosis, Hemophagocytic/drug therapy , Lymphohistiocytosis, Hemophagocytic/surgery , Male , Middle Aged , Rituximab , Splenectomy , Young Adult
12.
Clin Exp Immunol ; 150(2): 238-44, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17672869

ABSTRACT

There are limited data on the efficacy of T cell-based assays to detect tuberculosis (TB) antigen-specific responses in immune-deficient human immunodeficiency virus (HIV) patients. The aim of this study is to determine whether TB antigen-specific immune responses can be detected in patients with HIV-1 infection, especially in those with advanced disease (CD4 T cell count < 300 cells/microl). An enzyme-linked immunospot (ELISPOT) assay, which detects interferon (IFN)-gamma secreted by T cells exposed to TB antigens, was used to assess specific immune responses in a prospective study of 201 HIV-1-infected patients with risk factors for TB infection, attending a single HIV unit. The performance of the ELISPOT assay to detect TB antigen-specific immune responses is independent of CD4 T cell counts in HIV-1 patients. The sensitivity and specificity of this assay for the diagnosis of active tuberculosis does not differ significantly from values obtained in immunocompetent subjects. The negative predictive value of the TB ELISPOT test is 98.2%. A positive predictive value of 86% for the diagnosis of active tuberculosis was found when the combined number of early secretory antigen target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10) IFN-gamma spots to CD4 T cell count ratio was > 1.5. TB antigen-specific immune responses can be detected in HIV patients with low CD4 T cell counts using ELISPOT technology in a routine diagnostic laboratory and is a useful test to exclude TB infection in immune-deficient HIV-1 patients. A combination of TB antigen-specific IFN-gamma responses and CD4 T cell counts has the potential to distinguish active tuberculosis from latent infection.


Subject(s)
AIDS-Related Opportunistic Infections/immunology , Antigens, Bacterial/immunology , HIV-1 , Mycobacterium tuberculosis/immunology , Tuberculosis/immunology , AIDS-Related Opportunistic Infections/diagnosis , Adult , CD4 Lymphocyte Count , Enzyme-Linked Immunosorbent Assay/methods , Female , Humans , Immunity, Cellular , Interferon-gamma/biosynthesis , Male , Middle Aged , Predictive Value of Tests , Tuberculosis/diagnosis
13.
Eur Respir J ; 27(6): 1307-10, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16772392

ABSTRACT

Infection by Aspergillus species causes a wide spectrum of pulmonary disease in humans. In two patients with semi-invasive Aspergillus-induced lung disease, significantly reduced levels of interferon-gamma secretion by peripheral blood mononuclear cells were found after in vitro stimulation with the T-cell mitogen phytohaemagglutinin. Despite anti-fungal therapy, both patients exhibited progressive disease, and adjunctive interferon-gamma therapy was associated with significant clinical improvement. The data suggest that impaired production of interferon-gamma can be seen in patients with chronic pulmonary aspergillosis. Adjunctive cytokine therapy with interferon-gamma may be useful in patients with progressive disease despite adequate anti-fungal therapy.


Subject(s)
Aspergillosis/drug therapy , Interferon-gamma/therapeutic use , Lung Diseases, Fungal/drug therapy , Adult , Antifungal Agents/therapeutic use , Aspergillosis/immunology , Aspergillus fumigatus/drug effects , Bronchoalveolar Lavage Fluid/microbiology , Chronic Disease , Disease Progression , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Therapy, Combination , Female , Humans , Injections, Subcutaneous , Interferon-gamma/blood , Lung Diseases, Fungal/immunology , Middle Aged
14.
J Viral Hepat ; 11(5): 459-64, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15357653

ABSTRACT

We examined correlates of antinuclear antibody (ANA) positivity (ANA+) in individuals with chronic hepatitis C virus (HCV) infection and the effect of positivity on clinical outcome of HCV. Pretreatment sera from 645 patients from three centres in Sweden (n = 225), the UK (n = 207) and Italy (n = 213) were evaluated by indirect immunofluorescence on Hep-2 cells for ANA pattern and titre by a single laboratory. Liver biopsies were all scored by one pathologist. A total of 258 patients were subsequently treated with interferon monotherapy. There was a significant difference in the prevalence of ANA (1:40) by geographic location: Lund 4.4%, London 8.7%, Padova 10.3% [odds ratio (OR) = 0.66; 95% CI: 0.46-0.94; P = 0.023]. Duration of HCV infection, age at infection, current age, route of infection, viral genotype, alcohol consumption, fibrosis stage and inflammatory score were not correlated with ANA+ or ANA pattern. Female gender was correlated with ANA+ and this association persisted in multivariable analyses (OR = 3.0; P = 0.002). Increased plasma cells were observed in the liver biopsies of ANA-positive individuals compared with ANA-negative individuals, while a trend towards decreased lymphoid aggregates was observed [hazard ratio (HR) = 9.0, P = 0.037; HR = 0.291, P = 0.118, respectively]. No correlations were observed between ANA positivity and nonresponse to therapy (OR = 1.4; P = 0.513), although ANA+ was correlated with faster rates of liver fibrosis, this was not statistically significant (OR = 1.8; P = 0.1452). Low titre ANA+ should not be a contraindication for interferon treatment. Our observation of increased plasma cells in ANA+ biopsies might suggest B-cell polyclonal activity with a secondary clinical manifestation of increased serum immunoglobulins.


Subject(s)
Antibodies, Antinuclear/blood , Autoimmunity , Hepacivirus/immunology , Hepatitis C, Chronic/immunology , Adult , Antiviral Agents/therapeutic use , Biopsy , Cell Line , Female , Hepacivirus/classification , Hepacivirus/genetics , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/virology , Humans , Interferons/therapeutic use , Liver , Male , Middle Aged , Prognosis , Sex Characteristics
15.
Gut ; 53(9): 1274-8, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15306584

ABSTRACT

BACKGROUND: In coeliac disease (CD) patients, the dominant DQ2-Alpha-I-gliadin peptide recognised by CD4 T cells is contained within peptide sequence 57-73 (p57-73) of Alpha-gliadin. This peptide sequence is also located within a 33-mer protease resistant gliadin fragment and therefore is likely to play an important role in the pathogenesis of CD. AIMS: Our aim was to determine whether a B cell epitope was present within the immunodominant T cell epitope of Alpha-gliadin and, if so, to elucidate its sequence and determine the importance of deamidation and/or modification of the amino acid at position 65 for IgA binding. PATIENTS AND METHODS: A cohort of CD patients, disease controls, and healthy individuals were examined. Serum IgA antibodies to the native and modified p57-73 fragment of Alpha-gliadin were analysed using enzyme linked immunosorbent assays. Peptide scanning experiments were further used to elucidate the B cell epitope. RESULTS AND CONCLUSION: IgA antibodies to p57-73 were found in 29/72 (40.2%) endomysial antibody positive patients, all of whom had CD. The peptide antibody appeared to be present when patients were on a diet containing gluten and declined on a gluten free diet. The p57-73 antibody was very specific for CD (98%) and had a sensitivity of 56%. The amino acid at position 65 was not important for IgA binding but was crucial for T cell recognition of p57-73. Pentapeptide PXPQP emerges as a potentially strong candidate for the IgA binding motif in this region of Alpha-gliadin. This study shows that a significant proportion of newly diagnosed CD patients have an antibody response to the immunodominant T cell epitope.


Subject(s)
Celiac Disease/immunology , Epitopes, T-Lymphocyte/analysis , Gliadin/immunology , Immunoglobulin A/immunology , Amino Acid Sequence , CD4-Positive T-Lymphocytes/immunology , Celiac Disease/diet therapy , Enzyme-Linked Immunosorbent Assay/methods , Epitopes, B-Lymphocyte/analysis , Epitopes, T-Lymphocyte/immunology , Gliadin/genetics , Glutens/administration & dosage , Humans , Molecular Sequence Data , Peptide Fragments/genetics , Peptide Fragments/immunology
16.
Clin Infect Dis ; 36(9): e100-6, 2003 May 01.
Article in English | MEDLINE | ID: mdl-12715326

ABSTRACT

Three cases of chronic fatigue syndrome (CFS) that followed acute parvovirus B19 infection were treated with a 5-day course of intravenous immunoglobulin (IVIG; 400 mg/kg per day), the only specific treatment for parvovirus B19 infection. We examined the influence of IVIG treatment on the production of cytokines and chemokines in individuals with CFS due to parvovirus B19. IVIG therapy led to clearance of parvovirus B19 viremia, resolution of symptoms, and improvement in physical and functional ability in all patients, as well as resolution of cytokine dysregulation.


Subject(s)
Fatigue Syndrome, Chronic/therapy , Immunoglobulins, Intravenous/therapeutic use , Parvoviridae Infections/therapy , Parvovirus B19, Human/immunology , Adult , Fatigue Syndrome, Chronic/virology , Female , Humans , Male , Middle Aged , Treatment Outcome
18.
J Neurol Neurosurg Psychiatry ; 73(6): 739-46, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12438480

ABSTRACT

OBJECTIVE: To review the clinical and pathological features of parvovirus B19 meningoencephalitis and its sequelae in 12 previously published cases, and to perform additional tests to determine the pathogenesis of the disease. METHODS: Cases were reviewed and available serum and cerebrospinal fluid (CSF) tested for antiganglioside antibodies and a range of cytokines. In situ hybridisation for parvovirus B19 DNA was performed on postmortem brain tissue in two cases. HLA-DRB1 typing was undertaken on genomic DNA extracted from peripheral blood leucocytes. RESULTS: Cerebellar involvement was suggested either clinically or pathologically in four cases. In the two cases with postmortem histology, there was marked atrophy of the molecular and granular layers of the cerebellum with focal loss of Purkinje cells. Brain scanning by MRI or CT was done in six cases during the acute phase. Three were abnormal with evidence of demyelination. Three had markedly enlarged ventricles, in two of which there was high signal intensity from the white matter on both T1 and T2 weighted images. The three cases with abnormal brain scans had long term neurological sequelae (mental retardation, personality change, altered affect). In situ hybridisation on available postmortem brain tissue was negative in the two cases tested. All cases in which HLA-DR alleles were determined carried at least one of the following alleles: HLA-DRB1*01, *04, *07, *09, *15, *16. Available serum and CSF was tested for antiganglioside antibodies (all negative) and for a panel of cytokines, which had a similar profile in both serum (n = 5) and CSF (n = 1) during the acute phase. Cytokines that were consistently detectable were IL-6 (mean 726.20 pg/ml), TNFalpha (50.64 pg/ml), IFNgamma (39.64 pg/ml), GM-CSF (216.12 pg/ml), and MCP-1 (154.43 pg/ml); IL-1beta, IL-5, and IL-13 were undetectable. CONCLUSIONS: HLA-DR associations, an increased cytokine response, and benefit from immunomodulatory treatment (in one case) support a role for the immune response in the pathogenesis of parvovirus B19 meningoencephalitis.


Subject(s)
Alleles , Cytokines/physiology , Demyelinating Autoimmune Diseases, CNS/diagnosis , Erythema Infectiosum/diagnosis , HLA-DR Antigens/genetics , Meningoencephalitis/diagnosis , Parvovirus B19, Human , Adolescent , Brain/pathology , Child , Child, Preschool , Demyelinating Autoimmune Diseases, CNS/genetics , Demyelinating Autoimmune Diseases, CNS/immunology , Demyelinating Autoimmune Diseases, CNS/pathology , Erythema Infectiosum/genetics , Erythema Infectiosum/immunology , Erythema Infectiosum/pathology , Female , HLA-DRB1 Chains , Humans , Infant , Infant, Newborn , Magnetic Resonance Imaging , Male , Meningoencephalitis/genetics , Meningoencephalitis/immunology , Meningoencephalitis/pathology , Neurologic Examination , Tomography, X-Ray Computed
20.
J Occup Environ Med ; 43(3): 238-49, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11285872

ABSTRACT

We examined the relationship between exposure to beryllium and the presence of beryllium sensitization (BeS) and chronic beryllium disease (CBD) in a cohort of workers in a beryllium precision machining facility. Twenty workers with BeS or CBD (cases) were compared with 206 worker-controls in a case-control study. Exposure for each job title was measured using cascade impactors placed in the workers' breathing zone to measure total beryllium exposure and exposure to particles < 6 microns and < 1 micron in aerodynamic diameter. Cumulative exposure was calculated as sigma (job title exposure estimate x years in job title). Individual lifetime-weighted (LTW) exposure was calculated as sigma [(job title exposure x years in job title) divided by total years employment)]. Workers in the case group were more likely to have worked as machinists (odds ratio, 4.4; 95% confidence interval, 1.1 to 17.5) than those in the control group. The median cumulative exposure was consistently greater in the cases compared with the controls for all exposure estimates and particle size fractions, although this was not statistically significant. The median cumulative exposure was 2.9 micrograms/m3-years in the cases versus 1.2 micrograms/m3-years in the controls for total exposure, and 1.7 micrograms/m3-years in the cases versus 0.5 microgram/m3-years in the controls for exposure to particles < 6 microns in diameter. With cumulative exposure categorized into low-, intermediate-, and high-exposure groups, the odds ratios were 2.4 (95% confidence interval, 0.7 to 8.2) for the intermediate-exposure group and 1.2 (95% confidence interval, 0.4 to 4.2) for the high-exposure group compared with the low-exposure group. The median LTW exposure was 0.25 microgram/m3 in both groups. The median LTW exposure to particles < 6 microns was 0.20 microgram/m3 in the cases compared with 0.14 microgram/m3 in the controls. The differences in cumulative and LTW exposure were not statistically significant. None of the 22 workers with LTW exposure < 0.02 microgram/m3 had BeS or CBD. Twelve workers (60%) in the case group had LTW exposures > 0.20. In conclusion, increased cumulative and LTW exposure to total and respirable beryllium was observed in workers with CBD or BeS compared with the controls. These results support efforts to control beryllium exposure in the workplace.


Subject(s)
Berylliosis/etiology , Occupational Exposure , Occupations , Adult , Case-Control Studies , Chi-Square Distribution , Female , Humans , Logistic Models , Male , Middle Aged , Particle Size
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