[Immunologic desensitization].
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This study examined the possibility that there is cross-desensitization between immunologic and nonimmunologic stimuli that evoke contraction and histamine release (HR) in the isolated guinea pig trachea. Compound 48/80 and D-tubocurarine were found to cause homologous and heterologous desensitization for both contraction and HR from superfused trachea. Specific antigen challenge of trachea obtained from animals sensitized with either IgG1 (ovalbumin [OA]) or IgE (oxazalone-human serum albumin [OX-HSA]) also resulted in homologous desensitization for both contraction and HR. However, in experiments with animals sensitized with both IgG1 and IgE antibodies, prechallenge with OA resulted in cross-desensitization to OX-HSA, whereas the reverse sequence was ineffective in eliciting this phenomenon. This may be related to the type of desensitization produced by each antigen (specific versus nonspecific) or to heterogeneity of mast cells in the tissue. Prechallenge of the trachea with compound 48/80 or D-tubocurarine failed to alter subsequent effects of antigen after active sensitization with OA or passive sensitization with either IgG1 or IgE antibodies. Small but statistically significant decreases in tracheal responses to D-tubocurarine were observed after antigen prechallenge to active both IgG1 and IgE antibodies. This is the first study to demonstrate a cross-desensitization between compound 48/80 and D-tubocurarine and the first to examine cross-desensitization with IgG1 and IgE antibodies in the guinea pig trachea. The overall conclusion is that there is no major overlap in the desensitization mechanisms between immunologic and nonimmunologic stimuli in the guinea pig trachea.
The allergic dermal tests were carried out in 122 patients who were treated from June 1987 to August 1988. The positive rates for mycomutacapitis, myco-root-black, dust mite and artemisia pollemo were 37.5%, 34.5%, 34.2% and 21.88% respectively in inhaled antigens used for skin test. The positive rates for sesame, peanut, allium and garlic were rather high in food antigens used for skin test. The serum IgE and the total IgE tested by BA-ELISA and human basophil degranulation test (HBDT) were observed in 68 patients with allergic asthma and 52 healthy persons. It was found that the positive rate of BA-ELISA (82.35%) and HBDT (84.70%) coincided well with the dermal test. There was significant changes in serum level of the specific IgE and the total IgE before and after desensitizing therapy with the dust mite dermotaphagoides for 6 months (P less than 0.001).
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A 24-year-old white woman reported sexual intercourse-related pruritus, hives, wheezing, and dyspnea within 5 minutes after ejaculation. Systemic reactions (SRs) were prevented by use of condoms. Prick testing confirmed sensitization to five Sephadex G-100-separated fractions of her husband's seminal plasma. The intradermal end point threshold concentrations (ETC) were 10(-4) and 10(-1) micrograms of protein per milliliter to fractions 2 and 3, respectively. Leukocyte histamine release studies exhibited 100% release to fraction 2 and 37% release to fraction 3. A 2-day protocol of rapid immunotherapy (IT) was performed with subcutaneous incremental doses of human seminal plasma (HuSePl) fractions 2 and 3. The patient experienced an SR after receiving a cumulative dose of 38.55 micrograms of fraction 2 on day 1. On day 2, rapid IT with fraction 2 was administered until the patient experienced a mild SR after having received a cumulative dose of 102.8 micrograms. There was a one-log10 increase in the intradermal ETC to both fractions 2 and 3 at the end of day 2. IT was continued three times weekly for 4 months until the patient tolerated 100 micrograms doses of both fractions 2 and 3. At 4 months, coitus was resumed without SRs, and HuSePl IT was stopped. The intradermal ETC to fractions 1, 3, 4, and 5 was increased 6 months after cessation of HuSePl injections, but there was a one-log decrease in the ETC to fraction 2. Our experience demonstrated that systemic tolerance can be achieved by parenteral administration of selected HuSePl fractions. Partial immunologic desensitization of patients with anaphylactic sensitivity can be achieved.(ABSTRACT TRUNCATED AT 250 WORDS)
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Some immunological parameters were followed up during the first year of grass pollen desensitization in 15 patients. The skin reactions with grass pollen extract in a series of tenfold dilutions were diminished in all patients during treatment. In nearly all patients a distinct increase in blocking antibody titre was seen. Serum reagin titres as measured by RAST remained constant or decreased somewhat during desensitization. No significant correlations between all three parameters could be demonstrated.
The evidence in this presentation clearly indicates that in the case of the model disease EAE, desensitization procedures are effective in suppressing the symptoms of the disease and in providing protection against it. The antigens used in our studies are all synthetic materials immunologically relevant to the myelin encephalitogenic protein, but not encephalitogenic themselves. The most effective of these materials is a random basic copolymer of alanine, glutamic acid, lysine and tyrosine, denoted COP 1. The finding that the suppressive polymers show immunological cross-reactivity with the encephalitogenic protein provides a logical basis for the explanation of their suppressive activity in terms of an immunological desensitization mechanism. Our studies suggest that the effectiveness of COP 1 in preventing EAE results from the production of antigen-suppressor T cells, and/or from blocking MBP-specific effector T cells. The results of the clinical trial presented here show demonstrable improvement in the COP 1-treated patients as compared with the placebo subjects, particularly for those patients with less severe MS at the start of the treatment. Thus, although the evidence supporting the antigenic role of MBP in MS is not strong, COP 1, a synthetic polypeptide simulating some of the properties of MBP, appears to be effective in altering the course of MS and is of potential value as a modality for the treatment of this disease.
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A nurse anesthetist who had experienced four systemic allergic reactions attributed to penicillin exposure was safely and successfully desensitized to penicillin despite predominantly minor determinant allergy (benzyl penicilloate skin test was positive at 1:100,000 dilution of standard 10 mM solution). Because of unavoidable occupational exposure to penicillin, daily oral doses of penicillin were continued after hospital discharge in an effort to maintain clinical tolerance. Immunologic measurements throughout the long-term desensitization effort provided some evidence that in this patient, drug-induced mast cell desensitization is an ongoing dynamic process that is dose dependent and that skin mast cell reactivity recovers slowly over a period of many weeks after the short-term high-dose desensitization protocol. A dose-dependent state of clinical tolerance to inadvertent penicillin exposure has been safely maintained in this patient for 18 mo.
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