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Biomedical subjects

H M Chapel

Publications and source records attributed to H M Chapel.

At least 37 records · Page 2Linked to original sources
PubMed1996

Human cytomegalovirus infection is not increased in common variable immunodeficiency.

It has been postulated that human cytomegalovirus (HCMV) infection may have a role in the pathogenesis of common variable immunodeficiency (CVID). Many patients have a lymphocyte phenotype similar to that seen in HCMV infection, HCMV mononucleosis may precipitate hypogammaglobulinaemia, and a previous small study of common variable immunodeficient patients reported a high rate of active HCMV infection. This study investigated the presence and activity of HCMV infection in 102 CVID patients. Buffy coats were examined for the presence of HCMV IE and glycoprotein B genes using highly sensitive nested PCR. 30 blood donors of known HCMV serologic status were used as controls. There was no significant difference in HCMV positivity by PCR between patients and controls. Enrichment for mononuclear cells prior to PCR had no effect on sensitivity. Twenty-five patients were also examined for HCMV antigenaemia by staining buffy coat cytospins with monoclonal antibodies directed against the HCMV pp65 lower matrix protein, a technique widely used for diagnosis of active HCMV disease. Only one patient was positive (and also positive by PCR). Whilst these results do not exclude prior infection contributing to antibody deficiency in a small proportion of CVID patients, this study refutes the previously reported increase in active HCMV infection in CVID.

Adolescent↗
PubMed1996

Effects of intravenous immunoglobulin on muscle weakness and calcium-channel autoantibodies in the Lambert-Eaton myasthenic syndrome.

Intravenous immunoglobulin improves many antibody-mediated autoimmune disorders, but its mode of action is unknown. We investigated its effects on muscle strength and on the serum titer of the calcium-channel autoantibodies that are likely to be pathogenic in the Lambert-Eaton myasthenic syndrome (LEMS). In a randomized, double-blind, placebo-controlled crossover trial, serial indices of limb, respiratory, and bulbar muscle strength and the serum titer of calcium-channel antibodies in nine patients were compared over an 8-week period, using the area-under-the-curve approach, following infusion on two consecutive days of immunoglobulin at 1 g/kg body weight/day (total dose 2.0 g/kg body weight) or placebo (equivalent volume of 0.3% albumin). Calcium-channel antibodies were measured by radioimmunoassay using 125I-omega-conotoxin MVIIC. Direct anti-idiotypic actions of immunoglobulin were tested in this assay. Immunoglobulin infusion was followed by significant improvements in the three strength measures (p = 0.017 to 0.038) associated with a significant decline in serum calcium-channel antibody titers (p = 0.028). Improvement peaked at 2 to 4 weeks and was declining by 8 weeks. Mean serum titers were unchanged at 1 week, however, and direct anti-idiotypic neutralization by immunoglobulin was not demonstrable in vitro. We conclude that immunoglobulin causes a short-term improvement in muscle strength in LEMS that probably results from the induced reduction in calcium-channel autoantibodies. The reduction is not due to a direct neutralizing action of the immunoglobulin, but a delayed anti-idiotypic action cannot be excluded. Improvement following intravenous immunoglobulin in other autoantibody-mediated disorders may similarly be associated with decline in levels of pathogenic autoantibodies.

Adolescent↗
PubMed1995

Antibody responses and symptoms after DTP and either tetanus or diphtheria Haemophilus influenzae type B conjugate vaccines given for primary immunisation by separate or mixed injection.

The safety and immunogenicity of two conjugate Haemophilus influenzae type B (Hib) vaccines administered either mixed with, or in separate limbs to, a whole-cell DTP vaccine, was compared in infants vaccinated at 2, 3 and 4 months of age. Antibody titres to purified polyribosylribitol phosphate, diphtheria, and to pertussis antigens between infants who received the Hib and DPT vaccines in separate limbs or in the same limbs were similar (P > 0.1) while antibody titres to tetanus toxoid were higher in the later group (P < 0.05). This study demonstrated that both Hib vaccines can be mixed with whole-cell DTP vaccine without reducing immunogenicity of either vaccine or increasing the incidence of adverse reactions.

Antibodies, Viral↗
PubMed1995

Avidity of specific IgG antibodies elicited by immunisation against Haemophilus influenzae type b.

AIM: To investigate the avidity of specific IgG polyribosyl ribitol phosphate (PRP) antibodies induced by three Haemophilus influenzae type b (Hib) conjugate vaccines: PRP-meningococcal outer membrane protein complex (PRP-OMP), PRP-non-toxic mutant diphtheria toxin, CRM197 (HbOC) and PRP-tetanus toxoid (PRP-T). METHODS: One hundred and ten infants were immunised with one of the vaccines at two, three and four months of age. Blood samples were taken after each vaccination and serum stored at -20 degrees C. Serum samples collected after the third course (that is, at five months of age) were submitted to antibody avidity assessment, using a urea enzyme linked immunosorbent assay (ELISA). RESULTS: All three conjugate vaccines elicited IgG PRP antibodies of high median avidity. The resultant antibody populations were heterogeneous with regard to avidity, which in turn was independent of PRP antibody concentration. CONCLUSIONS: With the recent findings of a correlation between bactericidal killing and affinity, our data highlight the need for a protective level to be expressed qualitatively as well as quantitatively.

Antibodies, Bacterial↗
PubMed1995

Immunological factors and risk of infection in plateau phase myeloma.

AIMS: A series of patients with myeloma were investigated to assess whether immunological risk factors predisposing to serious infection could be identified. METHODS: Patients (n = 102) with predominantly plateau phase myeloma were monitored prospectively for infections. Immunological parameters including total non-paraprotein immunoglobulins and specific antibody titres were measured in all patients and compared with a control population of healthy individuals of a similar age; response to immunisation with Pneumovax II, tetanus and diphtheria toxoids and IgG subclasses were measured in a subgroup of 41 patients. Other characteristics investigated for any association with infection included age, sex, paraprotein type, disease stage, and chemotherapy. RESULTS: Specific antibody titres to pneumococcal capsular polysaccharides and tetanus and diphtheria toxoids were significantly reduced compared with the control population. Low antipneumococcal and anti Escherichia coli titres correlated with risk of serious infection and low anti-pneumococcal titres with severity of non-paraprotein immunosuppression. In 41 immunised patients responses to Pneumovax II, tetanus and diphtheria toxoids were poor; IgG subclass levels were significantly reduced and a poor IgG response to Pneumovax II immunisation was associated with an increased risk of septicaemia and low IgG2 levels. The overall serious infection rate was 0.92 infections per patient year and was four times higher during periods of active disease (1.90) compared with plateau phase myeloma (0.49). The predominant site of infection was the respiratory tract. Clinical and laboratory parameters showed only male sex and reduced non-paraprotein IgG and IgA levels to be significantly associated with at least one serious infection. CONCLUSIONS: A subgroup of patients with myeloma with poor IgG responses to exogenous antigens, who are at increased risk of serious infection, can be identified and may benefit from replacement immunoglobulin therapy to reduce the risk of infection.

Aged↗
PubMed1995

The use of rheumatoid factors in clinical practice.

Rheumatoid factor is a commonly requested test in the investigation of joint problems. Although the test has been found to be both sensitive and specific for rheumatoid arthritis in patients attending Rheumatology Clinics, when the test is applied to general hospital or community populations it performs poorly. Thus the setting in which rheumatoid factor tests are requested and awareness of the test's limitations are critical for appropriate use and interpretation of results. We studied 295 consecutive requests for testing at four centres. The majority were performed for the investigation of joint problems but only 6% of these were positive, suggesting unselective requesting. Half of the results were used to make diagnoses and influence management. However, significant numbers of clinicians felt that the test result had either excluded or confirmed a diagnosis of rheumatoid arthritis suggesting that results were being over-interpreted and that clinical decisions made on this basis may have been inappropriate. We conclude that in this setting rheumatoid factor testing is of limited value and generates misleading information.

Adolescent↗
PubMed1995

Management of primary antibody deficiency by consultant immunologists in the United Kingdom: a paradigm for other rare diseases.

Variation in clinical practice and its effect on outcome is little known for rare diseases such as primary antibody deficiency. As part of a national audit a survey of all 30 consultant immunologists in the United Kingdom dealing with primary antibody deficiency syndromes in adults and children was carried out in 1993 to ascertain their practices in diagnosis and management. Consensus guidelines were published after the survey was completed. Comparison of the survey results of clinical practice at the time the guidelines were published with the standards identified highlighted that the practice of a minority of specialists was at variance with their peers and with the consensus document, particularly in the use of intramuscular immunoglobulin, the dose and frequency of intravenous immunoglobulin, and target trough immunoglobulin G concentration, which has implications for the quality of patient care. However, much closer agreement existed in the key areas of management, such as diagnosis and selection of intravenous immunoglobulin. The approach and the problems identified are relevant to the management of other rare diseases, in which diagnosis and management is complex and there are few specialists with the necessary knowledge to undertake such care. This survey, the first attempted audit of practice, shows that within a motivated group of specialists highly significant differences in practice may exist and the authors emphasise the importance of setting clear guidelines against which care can be assessed.

Adult↗
PubMed1994

Randomised trial of intravenous immunoglobulin as prophylaxis against infection in plateau-phase multiple myeloma. The UK Group for Immunoglobulin Replacement Therapy in Multiple Myeloma.

Patients with plateau-phase multiple myeloma have an increased risk of life-threatening bacterial infections and polyclonal humoral immune suppression. We conducted a randomised, double-blind, placebo-controlled, multicentre trial of intravenous immunoglobulin (IVIg) as prophylaxis against infection. 82 patients with stable multiple myeloma received monthly infusions of IVIg at 0.4 g/kg body weight or an equivalent volume of placebo (0.4% albumin) intravenously for 1 year. Other interventions, including chemotherapy, were not affected; no patient received prophylactic antibiotics. There were no differences at entry or on study in clinical or laboratory variables between patients in the two groups. There were no episodes of septicaemia or pneumonia in patients receiving IVIg compared with 10 in placebo patients (p = 0.002). There were 57 serious infections; 38 occurred in 470 patient-months on placebo, compared with 19 in 449 patient-months on IVIg (p = 0.019). IVIg also protected against recurrent infections (p = 0.021) in 60 patients who completed a year. Before treatment, 54 patients were immunised with Pneumovax and specific IgG responses were measured. A poor pneumococcal IgG antibody response (less than 2-fold increase) identified patients who had maximum benefit from IVIg. Mild adverse reactions were noted in 12% of IVIg infusions and 5% of placebo infusions. IVIg can be given safely to plateau-phase myeloma patients. It protects against life-threatening infections and significantly reduces the risk of recurrent infections. The individuals who benefit most can be identified prospectively by measuring IgG antibody responses to pneumococcal immunisation.

Aged↗
PubMed1994

The use of intravenous immune globulin in multiple myeloma.

Patients with multiple myeloma suffer from serious bacterial infections throughout the course of the disease. This is probably associated with reduced polyclonal immunoglobulin synthesis. Prophylactic intravenous immune globulin (IVIG) reduces the incidence and recurrence of these infections in the stable phase of the disease. Infections at times of induction chemotherapy and/or relapse have a wider range of causative organisms. Such susceptibility may be associated with abnormal phagocytic function following chemotherapy.

Bacterial Infections↗
PubMed1993

Haemophilus influenzae type b carriage and immunity four years after receiving the Haemophilus influenzae oligosaccharide-CRM197 (HbOC) conjugate vaccine.

Late in 1991, before the implementation of a national immunization program against Haemophilus influenzae type b (Hib) in the United Kingdom, we performed a 4-year follow-up of 120 children who in 1987 had been enrolled in an immunogenicity trial in which 60 of them (vaccinees) received an Hib conjugate vaccine (HbOC) at the same time as diphtheria-tetanus toxoid-pertussis vaccine at the ages of 3, 5 and 9 months. Sixty others (controls) received only diphtheria-tetanus toxoid-pertussis vaccine at the same ages and were not subsequently immunized against Hib. We investigated Hib pharyngeal colonization using the antiserum agar method and the concentrations of serum IgG antibody to the type b capsule by enzyme-linked immunosorbent assay. At 4 years of age the Hib colonization rates in vaccinees and controls were 8% (5 of 60) and 5% (3 of 60), respectively. The children colonized with Hib had greater serum anti-capsular IgG concentrations than did noncolonized children (P < 0.001), and colonized vaccinees tended to have higher concentrations than colonized controls (P = 0.053). Regardless of Hib colonization status vaccinees had greater antibody concentrations than controls (P < 0.001). Forty-nine percent of vaccinees had an antibody concentration > 1 microgram/ml. There was an inverse relationship between the Hib colony count on culture and the serum IgG concentration. These data indicate that the increase in serum antibody concentration after immunization with an Hib conjugate vaccine is sustained and that immunization primes for a booster response on exposure to Hib. There may be a relationship between previous Hib conjugate immunization and the density of Hib colonization in children.

Antibodies, Bacterial↗
PubMed1993

Effect of beta propiolactone on specific antibody measurements by ELISA.

Serum samples from 30 HIV seronegative patients were treated with beta propiolactone (BPL) to determine whether BPL interfaces with ELISA for specific antibodies against protein and carbohydrate antigens. BPL had no discernible effect on specific antibody measurements by ELISA. With the measuring need for specific antibody measurements in the management of HIV seropositive patients, it is reassuring that this laboratory safety measure does not impair the reliability of results.

Antibodies, Bacterial↗
PubMed1993

Adverse effects of intravenous immunoglobulin.

The range of diseases in which intravenous immunoglobulin (IVIG) is effective has expanded significantly since its initial use in primary antibody deficiency. There are at present at least 17 preparations of IVIG in use worldwide with similar profiles of adverse effects. Infusion-related effects range in severity. Mild adverse reactions (headache, flushing, low backache, nausea, wheezing) are often associated with a fast infusion rate, and respond rapidly on slowing the infusion. Very rare episodes of life-threatening anaphylaxis may occur, particularly in those IgA-deficient patients with anti-IgA antibodies; such patients should receive an IgA-depleted preparation of IVIG. There are concerns with any blood product about safety in regard to viral transmission. The 4 outbreaks of non-A non-B hepatitis (probably hepatitis C) in the 1980s were associated with the use of particular batches of IVIG. The more recent exclusion of all anti-hepatitis C virus positive individuals from the donor pool, and the introduction of specific antiviral steps in the manufacture of IVIGs, should prevent further outbreaks. The human immunodeficiency virus (HIV) is effectively inactivated during the manufacturing process itself and HIV transmission has not been reported with IVIG. Rarely, haematological (Coombs' test positive haemolysis), neurological (aseptic meningitis) or renal (transient rises in serum creatinine) adverse effects may be seen when high doses of IVIG are used for immunomodulatory purposes. Haemolysis, due to passive transmission of blood group antibodies (anti-A, anti-D), may be prevented by selecting IVIG batches that give a negative cross-match between the recipient's red cells and IVIG.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗