Biomedical subjects
Publications and source records attributed to A G Bird.
A child with idiopathic pulmonary haemosiderosis for three years required three monthly transfusions. Circulating avian, gliadin, and reticulin antibodies suggested the diagnosis of gluten enteropathy, and jejunal biopsy showed subtotal villous atrophy. During 15 months on a gluten free diet his growth and behaviour improved and he required no transfusions.
A middle aged woman presented with acute, severe, intravascular coagulation leading to ischaemic necrosis of the extremities. Pulmonary involvement required artificial ventilation, and there was evidence of hepatic, pancreatic, and renal damage, which resolved without complication. These events may have been triggered by the ingestion of compound diuretic tablets. The finding of the 'lupus anticoagulant' and anticardiolipin antibodies, together with high titre antinuclear factor in the serum, and antibodies to extractable nuclear antigen (RNP), and a past history of spontaneous abortion, suggest that this was a dramatic manifestation of an immune connective tissue disorder.
The Analytical Methods Working Party of the Association of Clinical Biochemists (ACB) established this Task Force to consider the measurement of total serum IgE and specific IgE. The aims were to give general guidance on available methods of assay; to survey commercial kits and 'in-house' methods; to investigate performance based on external Quality Assessment and independent evaluation, and to advise on criteria laboratories should consider before setting up IgE and specific IgE assays.
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The distribution of IgG subclasses in the antibasement membrane zone autoantibody of pemphigoid in skin and serum was analyzed by use of monoclonal antibodies to human IgG subclasses. The predominant subclass was IgG4 which was present in 23 of 24 skin biopsies, IgG1 was next and IgG3 was found only occasionally. In 3 of 24 biopsies IgG4 was the only IgG subclass detected, C3 was absent in 2 of these, the third contained IgM and C3. Serum autoantibodies were similarly analyzed by indirect immunofluorescence (IIF) when again IgG4 autoantibody was the dominant subclass. No IgE autoantibody was detected by IIF.
Two cases are described in which patients developed acute anaphylactic reactions to precurarising doses of gallamine. Life threatening complications can arise from the use of small doses of drugs as adjuncts to anaesthesia and raises the question whether the benefits of precurarisation outweigh the risks of anaphylaxis.
The ability of cellulose-based (Cuprophan, saponified cellulose ester) and synthetic (polyacrylonitrile, polycarbonate, polymethylmethacrylate) haemodialysis membranes to activate complement during treatment was compared, using functional, immunochemical, radioimmunoassays, and fast centrifugal analysis assay techniques. Cellulosic and synthetic membranes show a striking similarity in their complement activation when measured by immunochemical assays. Functional haemolytic assays for alternate pathway and CH50 demonstrate no significant differences from predialysis values. C3d levels were also unable to demonstrate differences between the membranes. C3a levels, on the other hand, demonstrated significant differences between cuprophan, polyacrylonitrile, and polymethylmethacrylate but not between Cuprophan and polycarbonate membranes. Since comparable alternate-pathway activity of both cellulosic and synthetic membranes was demonstrated, but their C3a release differed, it is possible that certain surfaces that activate complement also possess the ability to absorb components of the alternate pathway.
The magnitude of leucopenia and complement activation when reusing cellulose based (Cuprophan) and synthetic (polyacrylonitrile AN-69S) haemodialysis membranes as well as their modifications by the priming of the dialysers with fresh frozen plasma and by the introduction of a period of stagnation during haemodialysis were studied using radioimmunoassay (C3a), centrifugal analysis (C3d), immunochemical (C3, Factor B) and functional (CH50 and alternate pathway) assays. Our findings demonstrate that complement activation and leucopenia induced by Cuprophan are linked and are modified when the membrane is reused, or primed with plasma protein. However, chemical exposure during reuse to sodium hypochlorite modifies these observations. Reuse of the AN-69S membrane resulted in no modification of either leucopenia or complement activity, but this membrane consistently demonstrated lower levels of C3a than observed with either first use or reused Cuprophan membranes.
Paraproteins have rarely been described in primary biliary cirrhosis. Eighteen patients were identified as having both antimitochondrial antibodies, and a significant paraprotein by screening 950 patients with either a previously known paraprotein or documented antimitochondrial antibodies. The clinical spectrum included 11 patients with proven or probable primary biliary cirrhosis and five with a plasma dyscrasia, of whom two also had primary biliary cirrhosis Antimitochondrial antibody activity appeared polyclonal and unrelated to the paraprotein class. Whilst in patients with primary biliary cirrhosis antimitochondrial antibody activity was predominantly of IgG3 subclass with normal levels, there was no subclass restriction shown in the remainder and IgG3 levels were lowered.
Among 377 patients with primary hypogammaglobulinaemia, mainly common variable immunodeficiency (CVID), 316 patients survived the first 2 years after diagnosis and were the subject of a study of cancer incidence. Among the 220 patients with CVID, there was a 5-fold increase of cancer due mainly to large excesses of stomach cancer (47-fold) and lymphomas (30-fold). The excess of stomach cancer is probably related to the high frequency of achlorhydria in CVID. 3 of the 7 patients with stomach cancer and CVID survived for 5 years or longer.
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Murine monoclonal antibodies ( McAbs ) with specificity for subclass-specific or subclass-restricted determinants on human IgG have been coupled to Sepharose to generate affinity columns. The judicial use of positive and negative chromatography and the exploitation of the special properties of individual McAb affinity columns has allowed the preparation of individual IgG subclasses from polyclonal IgG containing less than 1% contamination by any other IgG subclass. The specificity of the antibodies present in each polyclonal IgG subclass preparation has been assayed against a bacterial toxoid (tetanus), 2 bacterial cell wall antigens (E. coli and pneumococcal) and coat antigen(s) of a DNA virus (CMV). Antibodies were predominantly IgG1 to tetanus toxoid, IgG2 to pneumovax and E. coli cell walls, and IgG1, 2 and 3 to CMV coat antigens.
A technical modification of the protein A plaque assay is described in which the addition of polyethylene glycol 6000 results in increased sensitivity in detection of human immunoglobulin secreting cells. Optimal conditions for use of this modification are described which result in improved detection and visualisation of haemolytic zones and have, with continued use, been shown to improve the reproducibility and reliability of this assay.
In a 12-month study 301 patients referred to hospital consultants with putative allergic symptoms were tested for specific IgE antibodies to a panel of allergens and for total serum IgE levels. Examination of the data in relation to clinical information and the results of skin prick tests showed that the specific IgE antibody test has a limited role in the investigation of such patients.
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Epstein-Barr virus (EBV) will infect at least every third cell if exposed in vitro to an extensively purified B cell population from human peripheral blood. About 10% of such infected cells will be driven into immunoglobulin synthesis and secretion, as judged by the indirect protein A plaque assay. The appearance of EB nuclear antigen, de novo DNA synthesis, and immunoglobulin secretion are linked phenomena accompanying infection as judged by viral dilution experiments, which yield kinetics of a one-hit order. Induction of immunoglobulin secretion in B cells by EBV requires de novo synthesis of DNA, and consequently, nontransforming EBV (P3HR1) will not induce immunoglobulin secretion and will also specifically block such induction from subsequently added EBV. The termination of immunoglobulin induction by EBV in short-term cultures appears to be T cell dependent.
Cyclosporin A (CSA) is a fungal metabolite which exerts profound effects on the immune system and has potential as a selective immuno-suppressive agent. Clinical trials with human renal allograft recipients have confirmed this potential but there have been disturbing reports of lymphoma in a significant number of patients. Despite extensive animal studies, the specificity of this drug for human lymphocyte subpopulations is largely unknown. We demonstrate here that in vitro CSA has no apparent effect on Epstein-Barr virus (EBV)-induced B-lymphocyte activation, but totally inhibits the T-cell dependent pokeweed mitogen (PWM) B-cell response. In addition, CSA markedly facilitates the outgrowth of B-lymphoblastoid cell lines from both EBV-infected and non-infected lymphocytes of EBV immune donors cultured in vitro. These results indicate that CSA can interfere with the lymphocytes normally responsible for maintaining the life-long carrier state initiated by primary infection with EBV, allowing outgrowth of the persistently infected cells circulating in the peripheral blood.