Delayed hypersensitivity skin tests and subsequent renal transplant outcome.

BACKGROUND: Some studies in the literature have supported, while others have denied, the relationship between results of delayed hypersensitivity skin tests (DHST), renal allograft and patient survival rates. Several factors contribute to the unreliability of these studies. For example, most of these studies were performed in the precyclosporine era, furthermore, other variables which influence renal allografts and patient survival rates were not controlled in those studies. OBJECTIVE: The purpose of this study was to investigate the relationship between results of DHST performed in the pretransplant period with the subsequent renal transplant outcome in the cyclosporine era. METHODS: The study included 103 first cadaveric renal transplant recipients. DHST were performed during pretransplant evaluation by intradermal injections of a battery of recall antigens. Based on skin-test results, the patients were assigned to two groups--those with a positive skin test (STP+) and those with a negative (anergic) skin test. These two groups were compared with each other regarding allograft survival, patient survival, and other variables known to influence survival rates. RESULTS: The mean age, sex and racial distribution, degree of HLA matches between recipients and donors, number of acute rejection episodes, and number of patients with acute tubular necrosis were similar between the two groups. Renal allograft survival rates in the anergic group at 6 months, 1 year, 2 years, and 3 years were 97%, 90%, 84%, and 57%, respectively. The survival rate for renal allografts in the STP+ group for the same time points was 90%, 86%, 80%, and 72%, respectively. Patient survival rates for the anergic group at 6 months, 1 year, 2 years, and 3 years were 95%, 94%, 89%, and 85%, respectively, while those for the STP+ group were 98%, 98%, 98%, and 97% respectively. Differences between the STP+ and anergic groups, with regard to patient and allograft survival rates, were not significant. CONCLUSION: We conclude that DHST is not helpful in predicting outcome of patient or renal allograft survival rates over a 3-year time period.

Anaphylactic/anaphylactoid reactions to anaesthetic and associated agents. Skin prick tests in aetiological diagnosis.

Fifty-one patients were referred in one year (1992) for investigation of immediate type anaphylactic/anaphylactoid reactions during anaesthesia. Skin prick tests were made with 23 anaesthetic and associated agents in the concentrations used clinically. Definite or probable causes were identified by immediate type wealing reactions, supported by the clinical history in 36 of the 46 in whom a diagnosis of anaphylaxis was made. These comprised mainly the neuromuscular relaxants, chiefly suxamethonium (18); atracurium (6); gallamine (2); one each alcuronium; pancuronium; vecuronium and tubocurarine, as well as alfentanil (1); Gelofusine (2); cefuroxime (1) and latex (2). The materials for performing the skin prick test are readily available and it can be very helpful in making important aetiological diagnoses.

Allergic asthma to Bacillus subtilis enzyme: a model for the effects of inhalable proteins.

The passage of 24 years since the diagnosis of allergic asthma in heavily exposed workers and in a few consumers due to dusty enzyme preparations of Bacillus subtilis compounded with laundry powder makes it possible to review objectively the many problems it raised. It emphasizes the lessons to be learned, relevant to inhalable enzyme products and to other inhalable proteins in general. Occupational allergic respiratory diseases were little studied at the time and the enzyme problems stimulated interest in what has now become a well-established and important field of medicine involving not only protein allergens but low molecular weight chemicals as well.

Farmer's lung: thermophilic actinomycetes as a source of "farmer's lung hay" antigen. 1963.

Mouldy hay was produced in the laboratory by sterilising good hay, inoculating with aqueous suspensions of microorganisms, and incubating at 40 degrees or 60 degrees C. Extracts were tested for presence of farmer's lung hay (F.L.H.) antigen by agar-gel double-diffusion and immunoelectrophoresis tests against sixteen to twenty sera from patients with farmer's lung. F.L.H. antigen developed in hay after: (1) inoculating with mixed microbial suspensions from antigenically active hay; (2) inoculation with mixed suspensions of pure cultures of thermophilic actinomycetes, after raising the pH of the hay to 70 either by prior inoculation with fungi or by infiltration with ammonia vapour; and (3) inoculation at pH 70 with pure cultures of Thermopolyspora polyspora or with Micromonospora vulgaris. F.L.H. antigen did not develop in hay after inoculation with fungi only, or with six other actinomycetes tested, or after prior heating (though some sera reacted to fungal antigens in all these extracts). T. polyspora is the richest source yet found of F.L.H. antigen, and inhalation of an extract by affected subjects produces some of the features of farmer's lung. Pure cultures can produce F.L.H. antigen on artificial media without hay. Spores and mycelium are rich in F.L.H. antigen, and inhalation of the spores may play a part in farmer's lung disease. Other antigens relevant to farmer's lung may be found in other actinomycetes, not yet cultured.

Platinum group metal sensitivity: reactivity to platinum group metal salts in platinum halide salt-sensitive workers.

The ability of closely related platinum group metal salts (PGMS) to cross-react with the principal sensitising agent ammonium hexachloroplatinate IV was investigated in refinery workers. Selected subjects were screened by skin prick test, specific RAST, RAST inhibition, and primate PCA tests. These showed--but only in platinum-sensitive subjects--a low prevalence of skin and RAST sensitivity to the other PGMS and limited evidence of hapten specific cross-reactivity.

IgE antibody responses to platinum group metals: a large scale refinery survey.

All 306 South African platinum refinery workers (116 white, 190 coloured) accepted for employment on grounds of absence of evidence of atopy were investigated using the skin prick test and RAST to detect sensitivity to platinum, palladium, and rhodium salts. RAST studies were made for these, together with HSA and DNP-HSA RAST. Of the 306 workers, 38 had a positive skin prick test to the platinum halide salts; of these, one gave a positive reaction to the palladium salt and six to the rhodium salt. There were no isolated positives to the rhodium and palladium halide salts. Total IgE levels were raised in 24 of the 38 (63%) platinum salt prick test positive workers compared with only 43 of the 268 (16%) prick test negative group (p less than 0.001). Positive RASTs were obtained in 62% of those with positive skin tests to the platinum salts. Four of the six giving positive rhodium salt skin tests gave a positive RAST to rhodium salt. Of these, two gave positive RASTS to HSA and all four to DNP-HSA. The palladium salt RAST was negative in the single skin test reactor. In the platinum salt skin test positive group a raised HSA RAST was obtained in 10.5% compared with only 2.5% in the skin negative group. Twenty one per cent of the platinum salt skin positive group had a raised RAST score to DNP-HSA with only 3.5% (4/116) in the skin test negative group, of whom three also had a raised HSA RAST. The latter findings are suggestive of IgE antibody production to new antigenic determinants in HSA produced by conjugation with the platinum salts.

Enhancement of antibody production by mercury and platinum group metal halide salts. Kinetics of total and ovalbumin-specific IgE synthesis.

The effects of halide salts of mercury, platinum and palladium on the synthesis of total and specific serum IgE and of total IgG were studied in groups of Hooded Lister rats immunised with antigen (ovalbumin) in the presence and absence of an adjuvant (Bordetella pertussis vaccine or aluminium hydroxide). Repeated intraperitoneal injections of mercuric chloride alone rapidly enhanced total IgE levels in control rats, independent of adjuvant. Injections of the platinum salt, however, elevated total IgE levels more slowly and then only in the B. pertussis-treated group. The halide salt of palladium was ineffective. In rats immunised with antigen and adjuvant, mercury treatment rapidly produced enhancement of the titre-specific IgE antibodies, whereas treatment with platinum again raised these levels more slowly. The palladium salt had no such effect.

A longitudinal study of possible allergy to enzyme detergents.

One hundred and thirty-six subjects with asthma and/or hay fever were surveyed for possible sensitization to the Bacillus licheniformis protease present in the commercial antigenically identical enzymes (Alcalase and Maxatase) used in household detergents. Prick-test reactions reported as minimally positive were given by one subject to both commercial enzyme preparations at the same standard non-irritating concentrations and by four others to one but not the other antigenically identical enzyme. Two of the five, and an additional seven, gave weak prick tests to the purified enzyme (Koch-Light Protease) at test protein concentrations 100 times stronger and to which non-specific irritation occurs. The findings are strongly against interpretation of these reactions as positive and were on no occasion comparable with those in sensitive workers. The skin-test reactions are attributable to non-specific effects. Neither enzyme-specific RAST IgE tests nor clinical histories suggested clinical sensitivity. Enzyme-specific RAST IgE for eighty-eight subjects over a period of 5 years showed no correlation with exposure. None had developed specific IgE levels like those of sensitized workers, and their RAST levels did not differ significantly from cord blood, unexposed subjects and prick-test-negative workers. The eight with the largest increase in specific IgE were prick-test-negative and their clinical reactions to enzyme detergents were comparable to those of non-enzyme detergents. There is no evidence from this study that exposure to modern, non-dusty household enzyme-containing detergents is likely to lead to clinical sensitization.

Cross reactivity studies with platinum group metal salts in platinum-sensitised rats.

Hooded Lister rats were sensitised to the halide salt of platinum ammonium tetrachloroplatinate(II)[(NH4)2PtCl4] in its conjugated form with ovalbumin. Sensitisation was achieved by intraperitoneal injection with Bordetella pertussis vaccine as adjuvant, followed 21 days later by a further injection in saline. The presence of specific anti-platinum IgE antibody was determined by passive cutaneous anaphylaxis (PCA) and radioallergosorbent test (RAST) using the platinum halide salt conjugated to a heterologous carrier. Sera exhibiting positive reactions were pooled and PCA tests performed on the titrated pooled sera with 3 conjugated platinum group metal salts, 5 platinum group metals in their free salt form and 6 platinum salts with differing ligands. PCA challenges with these compounds resulted in significant cross reactivity between ammonium tetrachloroplatinate(II), ammonium hexachloroplatinate(IV) and the conjugated tetrachloroplatinate. There was very limited cross reactivity with other platinum or platinum group metal salts in either free or conjugated forms. Furthermore, these results were confirmed by RAST inhibition studies.

Immunological responses to complex salts of platinum. II. Enhanced IgE antibody responses to ovalbumin with concurrent administration of platinum salts in the rat.

The effect of platinum group metal salts on IgE antibody synthesis in an animal model was studied with respect to the magnitude and kinetics of the response. In outbred Hooded Lister Rats immunized with 10 micrograms ovalbumin with B. pertussis as adjuvant and boosted with 1 microgram in saline an enhanced secondary response to ovalbumin was obtained when certain halide platinum salts were given concurrently with primary immunization. This phenomenon was limited to ammonium tetrachloroplatinate II, ammonium hexachloroplatinate IV and to a lesser extent the cesium trichloronitroplatinate II. Platinum group metal salts not possessing this characteristic were cis-dichlorodiammine plantinum II, tetra-ammineplatinum II chloride, ammonium aquopentachlororhodate III and ammonium tetrachloropalladate II. Kinetic studies show that the time courses of the primary and secondary responses were not altered in the presence of the platinum salts. In rats immunized with ovalbumin without adjuvant there was no detectable antibody and concurrent administration of platinum salts also had no effects. Thus platinum salts whilst acting synergistically with adjuvant to enhance antibody synthesis do not act as adjuvants in their own right.

Skin tests.

Skin tests for cell-mediated immunity are useful in diagnosing immunodeficiency and in helping to give an accurate prognosis for many other diseases. They may also be used to assess the efficacy of immunosuppression regimens and the systemic effects of treatment.

Immunological responses to complex salts of platinum. I. Specific IgE antibody production in the rat.

Ammonium tetrachloroplatinate II ([NH4]2 PtCl4) was used in free and conjugated forms with ovalbumin in an attempt to elicit specific antibody directed against either the free platinum (Pt) salt or the platinum moiety of ovalbumin-Pt conjugates in the hooded Lister rat. Immunization with free Pt salt via intraperitoneal, intramuscular, intradermal, subcutaneous, intratracheal and footpad routes over a wide range of doses (1 microgram-1 mg) employing both B. pertussis and/or aluminium hydroxide gel as adjuvants failed to induce specific IgE antibody, either primary or secondary, as shown by direct skin, PCA test or RAST. Conjugation of (NH4)2 PtCl4 with ovalbumin produced conjugates, with between two and 10 haptenic Pt groups per ovalbumin molecule, capable of inducing IgE antibody directed against the Pt moiety as determined by heterologous PCA challenge, where carrier cross-reactivity was excluded, and by specific RAST, confirmed by RAST inhibition.

Systemic mastocytosis in a 5-year-old child: successful treatment with disodium cromoglycate.

Most clinical signs and symptoms of systemic mastocytosis (SM) are attributed to histamine release. We report here a 5-year-old male child with SM, who suffered from the age of 4 months from disseminated skin lesions, vomiting, diarrhoea, abdominal pain, flushing, tachycardia, hypotension, somnolence, and transient blindness, triggered by heat and egg ingestion. Oral disodium cromoglycate (DSCG) or placebo were started in a single blind trial at a dose of 100 mg/kg/day in four divided doses. The child was studied for 21 months during the administration of three courses of DSCG, each of 6 months' duration, interspersed with three 1-month courses of placebo. During treatment with DSCG all the systemic manifestations improved, and the histaminaemia decreased. During the placebo periods the symptoms, signs, and histaminaemia recurred.

Specific serum IgE antibodies to bacterial antigens in allergic lung disease.

A radio-allergosorbent test (RAST) to measure specific IgE antibodies in man to whole bacterial cells of Streptococcus pneumoniae, Staphylococcus aureus and Haemophilus influenzae was developed to investigate different well-defined lung diseases (chronic bronchitis, allergic bronchopulmonary aspergillosis (ABPA), bronchial asthma allergic rhinitis, cystic fibrosis) and also in urticaria as compared with non-atopic blood donors. In addition, total IgE values and skin prick tests were assessed in these patients. The ABPA group gave the highest specific IgE RAST scores to all three bacteria, whilst the chronic bronchitis and cystic fibrosis groups also gave raised RAST scores with H. influenzae. There was a positive correlation between the patients' Sta. aureus and Str. pneumoniae immediate-type skin reactions and their RAST scores and total serum IgE concentrations, but there was only a low incidence of immediate-type skin test positivity to H. influenzae.