Efficacy and safety of preseasonal-specific immunotherapy with an aluminium-adsorbed six-grass pollen allergoid

BACKGROUND: The clinical efficacy and safety of a six-grass pollen allergoid has been studied. The advent of more exacting clinical guidelines and a better appreciation of the possible mechanisms of treatment prompted this reappraisal. METHODS: A 2-year double-blind multicentre placebo-controlled phase 3 clinical trial was undertaken in 154 patients suffering symptoms of rhinoconjunctivitis with or without asthma (GINA I or II). Therapy comprised two consecutive preseasonal short-courses of subcutaneous injections using a grass pollen allergoid adsorbed to aluminium hydroxide. RESULTS: A combined symptom and medication score (SMS) was used as the primary end-point for clinical efficacy. SMS from the first year showed a significant difference of 26.6% between the two study groups (P=0.026) and this was improved after the second year when there was a 48.4% difference in SMS between active and placebo treatment in favour of the allergoid (P = 0.018). Highly significant increases in grass pollen allergen-specific IgG1 and IgG4 antibody concentrations were measured in association with active treatment. Allergen tolerance was increased as judged by a conjunctival provocation test and significant improvements in quality of life were documented using a standardized questionnaire. The allergoid was well tolerated. CONCLUSIONS: The grass pollen allergoid was shown to be safe and clinically efficacious in the management of hay fever with or without asthma (GINA I or II).     

Recurrent pericarditis: a rare complication of allergen immunotherapy

We report on a 29-year-old woman suffering from hay fever due to grass and olive tree pollens. She developed recurrent pericarditis during her first course of immunotherapy with an alum-adsorbed pollen extract. A causal relationship was established between the allergen injections and the acute pericarditis episodes on two consecutive occasions, which presented with blood eosinophilia. Blood cultures and serological tests for microorganisms were negative. There were no signs of autoimmune disease or systemic vasculitis. To the best of our knowledge, allergen immunotherapy-induced pericarditis has not been previously reported.     

Molecular cloning and sequence analysis of full-length cDNAs encoding new group of Cyn d 1 isoallergens

BACKGROUND: Cyn d 1, the major allergen of Bermuda grass pollen, contains some acidic/basic isoforms. The N-terminal amino acid sequences of some acidic Cyn d 1 isoforms were found to be different from those of Cyn d 1 cDNA clones identified previously. METHODS: A predicted 17-meric oligonucleotide probe was designed to fish the unidentified isoallergen cDNAs out of BGP cDNA library. The reactive clones were isolated and verified by sequencing. Two of them were expressed in the yeast Pichia pastoris to obtain recombinant Cyn d 1 proteins. RESULTS: All four cDNA clones encode the full-length Cyn d 1 with mature proteins of 244 amino acid residues. A 97-99% identity was found among the deduced amino acids of these four clones while an 86% identity was elicited between the four clones and the ones previously identified. The predicted isoelectric focusing (pI) values of the newly identified Cyn d 1s are acidic while pIs of the previously identified Cyn d 1s are basic. The two recombinant acidic Cyn d 1 proteins possess the epitopes recognized by mouse and rabbit polyclonal anti-Cyn d 1 antibodies, and have human IgE-binding capacity as revealed by immunodot assay. CONCLUSIONS: The present study identified full-length cDNAs encoding new isoallergens of Cyn d 1, and separated Cyn d 1 gene into an acidic group and a basic group.     

Olive pollen allergen Ole e 8: identification in mature pollen and presence of Ole e 8-like proteins in different pollens

In a first approach, Ole e 8, a novel Ca2+-binding protein from olive pollen, was cloned and produced in Escherichia coli. We have obtained the natural form of Ole e 8 (nOle e 8) from the pollen and examined its immunologic equivalence with its recombinant form (rOle e 8). Size exclusion chromatography and a phenyl-Sepharose CL-4B affinity column were used to obtain nOle e 8 from the olive pollen. Inhibition assays by immunoblotting, using rOle e 8-specific rabbit antiserum, were performed to analyze the immunologic equivalence between the natural and the recombinant allergen, as well as to detect its presence in other pollens. Recombinant and natural Ole e 8 resulted immunologically equivalents, since they completely inhibited the IgG binding of the polyclonal antiserum to each other. Ole e 8-like proteins were detected in Oleaceae and Juniperus communis pollen, and might contribute to cross-reactivity processes between taxonomically related pollens.     

Action of allogeneic and syngeneic splenic extracts on primary cell cultures from inbred mice

The effect of allogeneic and syngeneic extracts from the spleens of male and female inbred mice on primary cultures of fibroblasts obtained from the subcutaneous connective tissues of fetuses of CBA and C57BL/6J mice was studied. The cytotoxic and growth-inhibiting action on the cultures was successively enhanced by the use of extracts from syngeneic male and allogeneic female and male tissues. Consequently, an increase in the degree of antigenic difference between the target cells and extracts led to enhancement of the phenomenon of allogeneic inhibition. It was shown for the first time that in a syngeneic system extracts from male tissues (containing the weak H-Y antigen) have a cytotoxic action on cells from female inbred mice, i.e., that they induce a reaction of the allogeneic inhibition type.Research Laboratory of Experimental Immunobiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR N. N. Zhukov-Verezhnikov.) Translated from Byulleten' Éksperimental'noi biologii i meditsiny, Vol. 86, No. 10, pp. 486–488, October, 1978.     

Sensitization to cross-reactive carbohydrate determinants in relation to alcohol consumption

Background Alcohol consumption is associated with increased serum IgE of unknown specificity. Objective To investigate the prevalence of specific IgE to cross‐reactive carbohydrate determinants (CCDs) in adults, and its relation to alcohol consumption. Methods Population‐based survey of 457 adults (218 abstainers, 195 light‐to‐moderate drinkers, 44 heavy drinkers). Specific IgE determinations included a CCD (MUXF³, the N‐glycan of bromelain), pollens (Lolium perenne and Olea europaea), Hymenoptera venoms (Apis mellifera and Vespula spp.), and a mite (Dermatophagoides pteronyssinus). We replicated these studies in an additional sample of alcoholics (n=138). Inhibition assays were performed in selected cases. Results In the general population, 5.6% of individuals (95% confidence interval 3.5–7.6%) showed positive (0.35 kU/L) CCD‐specific IgE. The levels of CCD‐specific IgE were particularly high in heavy drinkers, who also showed a high prevalence of positive IgE to pollens and Hymenoptera venoms, doubling (at least) the prevalence found in alcohol abstainers and light‐to‐moderate drinkers. The presence of IgE to pollens and Hymenoptera venoms was closely correlated with the presence of CCD‐specific IgE. These features were confirmed in the additional sample of alcoholics. Inhibition studies indicated a role of CCD interference in IgE positivity to pollen and Hymenoptera allergens in alcoholics. Conclusions CCD‐specific IgE is prevalent in heavy drinkers, and is associated with positive IgE to pollens and Hymenoptera venoms. Specific IgE results should be interpreted with caution in heavy drinkers.     

Sinus CT scans and mediator release in nasal secretions after nasal challenge with cypress pollens

BACKGROUND: Involvement of paranasal sinuses has been suggested in allergic rhinitis but not clearly demonstrated. AIMS: To investigate the relationship between intermittent allergic rhinitis and computerized tomography (CT). METHODS: Twenty patients with intermittent rhinitis and sensitized to cypress pollens underwent unilateral nasal provocation tests (NPTs) using increasing concentrations of cypress pollens out of the pollen season. Sinus CT-scans were carried out just before a NPT and 24 h later. Nasal lavage was carried out just before a NPT, 30 min after a positive challenge and again 24 h later. Leucotriene C4/D4, intracellular adhesion molecule-1 and eosinophil cationic protein were measured in nasal secretions. RESULTS: Thirteen patients (65%) showed an alteration in their CT-scans after allergen challenge. Ten of them showed sinus changes controlateral to their allergenic provocation. Radiological changes mainly affected the osteomeatal complex and the ethmoid sinuses. Pre-existing abnormalities (13 of 20 cases) mainly concerned the maxillary sinuses. There was no correlation between CT-scan abnormalities and levels of mediators released in nasal secretions. CONCLUSIONS: We have shown that nasal allergen challenge can produce radiological changes in the paranasal sinuses. This mainly concerned the ethmoid sinuses.     

Caudal end of the rat spinal dorsal horn

We have previously demonstrated that the transformation of the caudal spinal cord through the conus medullaris to the filum terminale takes place in three steps. In the conus medullaris the twin layers of CGRP-immunoreactive and IB4-labeled primary afferent fibers as well as the translucent portion of the superficial dorsal horn equivalent to the substantia gelatinosa discontinue before the complete removal of the dorsal horn. Parallel with these changes VGLUT1-immunoreactive myelinated primary afferent fibers arborize not only in the deep layers but also in the entire extension of the remaining dorsal horn, while scattered CGRP fibers still remains at the margin of and deep in the dorsal horn. PKCgamma-immunoreactive dorsal horn neurons discontinue parallel with the disappearance of the IB4-labeled nerve fibers. These observations suggest that in the dorsal horn certain neurons are linked to the substantia gelatinosa, while others are substantia gelatinosa-independent neurons.     

Physostigmine and norepinephrine: Effects of injection into the amygdala on taste associations

The present investigation was conducted to determine whether norepinephrine or acetylcholine systems of the amygdala could be involved in two adaptive feeding behaviors in the rat: development of taste aversion and recovery from neophobia. In a taste aversion paradigm, a single bilateral injection of physostigmine directly into the amygdala at the onset of an apomorphine-induced illness experience produced a time-dependent attenuation in the development of taste aversion; in contrast, norepinephrine had no disruptive effects. In a neophobia paradigm, norepinephrine injected directly into the amygdala after a novel taste experience resulted in a time-dependent attenuation in recovery from neophobia; however, physostigmine produced no disruptive effects. Hence, acetylcholine appears to mediate taste-illness associations, while norepinephrine plays an important role in recovery from neophobia, i.e., taste-“learned safety” associations.     

Immunologic events in pigeon breeders'' disease

The immunologic and physiologic status of a group of symptomatic and asymptomatic pigeon breeders was studied in an attempt to define the immunologic events occurring in pigeon breeders' disease. Antibody activity to antigen(s) present in pigeon dropping extract (PDE) and pigeon serum (PS) was detected in the serum of both symptomatic and asymptomatic breeders. Antibody activity, however, tended to be greater in the symptomatic pigeon breeders. When subjects were challenged with PS via aerosol, serum complement activity became depressed only in asymptomatic patients. Cellular hypersensitivity to antigens present in PDE was detected in vitro in peripheral lymphocyte populations of 4 of 5 symptomatic breeders and in none of the asymptomatic breeders; cellular hypersensitivity to antigens in PS was not demonstrated in any of the individuals tested. These findings indicate that cell-mediated hypersensitivity, as well as humoral immunologic processes, may be involved in the pathogenesis of the hypersensitivity pneumonitis found in pigeon breeders.