Skin-window-induced inflammation in breast cancer patients: a study of macrophage migration.

A decreased number of macrophages has previously been demonstrated by means of skin-window assays in operable breast cancer patients. However, in this type of cellular inflammatory response, a varying intensity of cellular activation, cellular recruitment and macrophage chemotaxis exists. In this study, we performed skin windows after stimulation by a chemo-attractant (FMLP) and a recall antigen (Candidin-latex). Cellular responses were classified in 19 breast cancer patients according to the presence (A+) or absence (A0) of macrophage activation by comparison to healthy controls. In 13 A0 patients, the admixture of a cytokine (IFN alpha) and an immunomodulator (P40) to one agent or the other or both resulted in the restoration of macrophage functions. Our study shows that uniform cellular responses to chemo-attractants and antigens are observed in healthy and not immunocompromised individuals as assessed by skin-window tests. However, the cellular response recorded in immunodeficient cancer patients is altered. It also shows that the admixture to chemoattractants and antigens of particular cytokines or better still of an immunomodulator displaying a wide spectrum of activity offers a way of restoring macrophage functions. Individual responses to immunotherapy in clinical oncology may be related to such results.

Immunological investigation and immunotherapy in patients operated on for breast carcinoma.

The tumor-host relationship is an essential factor in the onset, development, and recovery from malignancies. A basic consideration in the treatment of cancer patients must therefore be to understand this relationship and attempt to modify it in order to favor the host. We here discuss the results of a study of the immunologic status of 91 breast cancer patients. The use of a battery of tests with five subcutaneous hypersensitivity antigens allowed us to detect some differences in the immunological profiles of patients with or without lymph node involvement. The effect of an immunostimulant fraction prepared from Corynebacterium granulosum, P40 is also analyzed. This fraction significantly modifies tumoral recurrence in DMBA-induced mammary cancers in the Sprague Dawley rat, causes regression of mammary permeation nodules following in situ injection and modifies the cutaneous reactions of one-half of the anergic breast cancer patients although regular re-challenge is still necessary.

[Treatment of recurrent urogenital infections by immunomodulation]. / Traitement des infections urogénitales récidivantes par immunomodulation.

In recurrent urogenital infections in which no curable cause can be found, long term antibiotic therapy is often the only possible form of treatment. After performing appropriate skin tests, the authors evaluated the effectiveness of vaccination consisting of antigen therapy and an immunostimulant, P 40, in 20 patients. The recurrent infections were controlled in the cases in which this combination was used; in half of the cases, maintenance vaccination was required for a period of 2 or 3 years.

[Microbial allergy and immunotherapy in allergologic practice]. / Allergie microbienne et immunothérapie en pratique allergologique.

Microorganisms (viruses, bacteria, fungi) may play a prominent role in triggering allergic manifestations. Either indirectly by releasing potentiating or immuno-modulation factors such as L.P.S. and peptidoglycans, or more directly by their numerous histamine--releasing potentials. However a difficulty remains to establish the relevance of such inter-relationships. The near future will probably give rise to better defined components from microbial origin, with a higher degree of specificity.

[Questions raised by the clinical and biological polymorphism of atopic dermatitis]. / Questions posées par le polymorphisme clinique et biologique de la D.A.

AD is not clearly located amongst the diseases of allergy, but it has some common features with respiratory tract allergy. 1. The disregulation of IgE and also T cell abnormalities. 2. Long-lasting inflammatory flare-up of AD resembles more delayed-type mechanisms of hypersensitivity than the precocious immediate type of respiratory allergy. Furthermore, the accumulation of inflammatory cells (PMN and monocytes-macrophages) in the sites involved in AD have not yet been thoroughly investigated. 3. Another feature of AD is its frequent association with respiratory tract allergy, though the immediate type reactions observed with respiratory symptoms are not necessarily linked by common mechanisms to AD cutaneous lesions. 4. Cutaneous lesions that suggest AD are often seen in disorders where there are genetic abnormalities, though in spite of a common eczematous aspect, the etiology and prognosis are entirely different from AD.

Cutaneous basophil hypersensitivity in atopic dermatitis.

The infiltration by basophils into delayed hypersensitivity skin test sites was examined in patients with atopic dermatitis, contact dermatitis and in normal healthy persons. Atopic dermatitis patients, with large amounts of IgE, injected intradermally with staphylococcal antigens showed reactions that were more transient and erythematous than those of normal persons. On histological examination there were numerous, degranulating basophils among the perivascular mononuclear cells. Normal persons, with small amounts of IgE showed typical mononuclear cell infiltration and few basophils. Patients with contact dermatitis, one with much IgE, responded to patch tests to potassium dichromate or to nickel sulphate by delayed type reactions, but on histology, two of the four patients showed a significant infiltration by basophils. It is considered that the erythematous response to the antigen in atopic dermatitis patients is related to the basophil infiltration.

Staphylococcal and human dander IgE antibodies in superinfected atopic dermatitis.

Ten patients (Group 1) with Staphylococcus aureus superinfected atopic dermatitis (SAD) were compared with three control groups without SAD. One control group (Group 2) was comprised of ten atopic patients with total IgE levels of greater than 1000 u/ml, another control group, of six atopic patients (Group 3) with total IgE levels of less than 1000 u/ml and a third group, of ten non-atopics (Group 4), five of whom were infected with Staphylococcus aureus. Total and specific anti-staphylococcal IgE levels and anti-human dander IgE were high in Group 1. Specific IgE levels to S. aureus were slightly increased in some Group 2 patients but were normal (less than 7%) for Group 3. No specific IgE to human dander antigen was detected in either Group 2 or Group 3. In the non-atopic control group (Group 4), six out of ten patients had both low total, and specific IgE antibodies to both staphylococcal, and human dander antigens. Two had increased total IgE and specific anti-staphylococcal IgE antibodies, and two more with a severe, chronic infection, also had anti-staphylococcal IgE antibodies. In SAD patients, a good correlation was seen between cutaneous basophil hypersensitivity and high specific IgE antibodies against staphylococcal and human dander allergens. Delayed type hypersensitivity reactions to staphylococcal antigen were negative or poorly positive in the SAD group by comparison to controls. A paradoxical anaphylactic type of response to the offending bacterial agent in SAD patients, associated with 'auto-atopy' to human dander, is discussed.

[Allergens adsorbed on aluminum hydroxide preparation, standardization controls and therapeutic results]. / Allergènes adsorbés sur hydroxyde d'aluminum: preéparation, standardisation, côntroles et résultats thérapeutiques

Specific desensitizing treatments with house dust extract purified and adsorbed on aluminium hydroxyde gave 79% good and very good results in 355 patients. Grass pollen extracts adsorbed on the same adjuvant gave 76% good and very good results in 166 patients. Desensitization by the adsorbed preparations requires fewer injections than the usual methods, while offering security by the absence of anaphylactic reactions, particularly with pollen extracts. The activity of the preparations is tested after appropriate dilution, taking account of the total nitrogen content of the dust extracts and the weight of raw materials used in the manufacture of the pollen extracts. The results of the intradermal tests undertaken with fluid preparations and compared with those obtained with a standard preparation allow to standardize the allergenic activity of the extracts. It is thus possible to guarantee the pharmaceutical quality of the allergens both for diagnostic tests and for treatments. Chemical analyses and control of acute, delayed or chronic toxicity ensure the innocuousness of the preparations.

Does reversed-type anaphylaxis in healthy subjects mimic a real allergic reaction?

Immediate and late cutaneous reactions were induced in healthy and atopic subjects by anti-IgE challenge and a skin-window technique was used in order to verify if the pattern of cells observed at 24 hr was similar in both groups. The study was first performed under basal conditions, and in a second double-blind cross-over step, it was performed again during treatment with cetirizine 10 mg b.i.d. and terfenadine 60 mg b.i.d. Anti-IgE challenge was followed by a significant eosinophil accumulation in atopic subjects only. Cetirizine significantly inhibited this phenomenon while terfenadine showed a mild non-significant inhibitory effect.

Reactivity of human basophils to anti-IgE and protein A in atopic dermatitis.

We compared by basophil degranulation and histamine release the reactivity to protein A and anti-IgE of the basophils from 3 groups of patients: group I (blood donors), group II (rhinitis) and group III (atopic dermatitis). We demonstrated that histamine release and basophil degranulation gave tightly correlated results and that by both methods group III was significantly (p less than 0.01) more sensitive to the effectors than the two other groups. Protein A and anti-IgE stimulation curves showed a rebound effect at low concentrations of effectors. This was, however, only significant (p less than 0.01) for group III. Bacterial hypersensitivity may be IgE-mediated and may be related to the increased sensitivity to bacterial antigens and the severity of atopic dermatitis in patients infected by Staphylococcus aureus.

Skin eosinophilia in atopic patients.

The responses of six atopic and six control patients to the intracutaneous administration of platelet-activating factor (PAF) acether, of the leukocyte secretagogue and chemoattractant f-methionyl-leucyl-phenylalanine (FMLP), and of allergens were studied. Immediate wheal-and-flare skin reactions to allergens and to PAF acether in atopic patients were the same, and when reactions were compared to reactions of nonatopic patients, these reactions to PAF acether and to FMLP were of equivalent intensity. Late-phase reactions were not observed macroscopically with allergen, PAF acether, or FMLP. The cellular responses, assessed by the Rebuck skin window technique, demonstrated a late (24 hours) eosinophilic response to the allergen and to both inflammatory agents, with 33% to 44% of intensively degranulated eosinophils. In comparison, very few, if there were any, eosinophils were observed in the nonatopic patients. Most infiltrated cells were neutrophils. The accumulation of eosinophils in atopic human skin indicates a potent eosinophilotactic activity restricted to the allergic patients. A similar cellular reaction has been observed in lungs from guinea pigs injected with PAF acether or with allergen, and in patients with severe asthma. The chemoattractant activity of FMLP toward eosinophils cannot be accounted for by its histamine-releasing activity and remains to be explained.

Activity units for allergen extracts.

The two present systems of units for the strength of allergen extracts, Noon and p.n.u. are both unsatisfactory. A new activity unit, based on skin prick in humans, is described, and its relationship to in vitro tests is explored. Potency limits for provocation materials used for skin prick tests are suggested.

Studies on untoward reactions to diphtheria and tetanus toxoids.

Adverse reactions to diphtheria and tetanus toxoids have frequently been reported. The cause of these reactions has been attributed to different factors, including sensitization by prior vaccination. However, this explanation does not hold for primary vaccination. In this case, undesirable reactions to diphtheria toxoid are most likely due to bacterial cellular fractions present in the vaccines. In fact, we were able to demonstrate that fortuitous contact with atoxigenic diphtheria strains can induce sensitization. Consequently, vaccination should be carried out with highly purified toxoids, so as to prevent untoward reactions due to the presence of impurities. It is also preferable to detoxify purified toxins, rather than to purify crude toxoids.

Immuno-enzymatic study of IgG subclasses specific for allergen in house dust immediate hypersensitivity.

Investigation of the serum-specific IgE by the RAST technique and of the four specific subclasses of IgG in house dust allergy by an immuno-enzymatic assay was made among healthy control subjects, non-treated atopic patients and hyposensitized patients. There was evidence that the titer of specific IgE remains high in the treated patients regardless of their improvement or non-improvement clinically. A good prognostic significance, however, correlates with a low specific IgG4 titer in the serum, but the pathogenic significance of IgG4 cannot be determined until these immunoglobulins can be studied on the membrances of circulating basophils of hyposensitized patients.

Cellular histamine release, specific and total serum IgE levels in hay fever patients and controls.

The amount of histamine released from blood leucocytes by allergen, the amount of allergen required to release 50% histamine and the total IgE and IgE specific for Dactylis glomerata are compared in nine hay fever patients and five control individuals. The variation with time of total IgE, of specific IgEe and of the percentage of histamine released at a fixed allergen concentration, corresponding to the cellular sensitivity, is shown for one control individual with positive in vitro and skin tests, but without clinical symptoms. For four patients with a low total IgE level the evolution of these parameters during a 1 year treatment period is presented.