Repeat syphilis has a different immune response compared with initial syphilis: an analysis of biomarker kinetics in two cohorts.

OBJECTIVE: We aimed to asses if there are differences in the clinical presentation and immune response of repeat as compared with initial syphilis. METHODS: Prospective study: we prospectively recruited all patients with a new diagnosis of syphilis and tested their plasma for a range of cytochemokines and rapid plasma reagin (RPR) at baseline pretreatment and 6 months following therapy. Retrospective study: we compared RPR assay response kinetics between initial and repeat syphilis in persons attending our HIV/STI clinic from 1993 to 2016. RESULTS: Prospective study: a total of 91 individuals, 36 with initial syphilis and 55 with repeat syphilis, were included in the study. At baseline visit, those with initial syphilis were more likely to be symptomatic and have higher levels of interleukin-10 than repeaters. At baseline, median RPR titres were higher in the repeat than the initial infection groups. Repeaters were less likely than those with initial infections to serorevert to a negative RPR and be serofast (<4-fold RPR titre decline) at 6 months.Retrospective study: syphilis was diagnosed in 1027/43 870 individuals tested. At diagnosis, repeaters had higher RPR titres and a stepwise increase in RPR titre with number of syphilis episodes. They had a different RPR test response kinetic: they were less likely to be serofast and to serorevert than initial syphilis at 6 and 12 months. No individuals with four or more previous episodes of syphilis seroreverted. CONCLUSION: Repeat syphilis has a different clinical presentation and immunological response to initial infection.

Identification of IgE.

Progress in protein chemistry in the 1950s revealed that the biologic activities of proteins, such as hemoglobin and enzymes, are based on partial structures in the protein molecules. This principle suggested to us the possibility that the human antibodies responsible for induction of reaginic hypersensitivity reactions might have unique structures that are lacking in the antibody molecules involved in immunity and that the differences in the structures of human antibody molecules can be recognized by the immune systems of experimental animals. Our studies were based on the hypothesis that reaginic antibody activity is associated with a unique immunoglobulin isotype, which is now called IgE. As expected, identification of IgE facilitated the analysis of immunologic mechanisms of reaginic hypersensitivity. Subsequent studies revealed that IgE specifically bound to basophilic granulocytes and mast cells through the Fc portion of the molecules and that cross-linking of the cell-bound IgE antibody molecules by allergen induced the release of bioactive mediators, such as histamine and leukotrienes, which initiate allergic reactions.

[Blood transfusion and inflammation]. / Transfusion sanguine et inflammation.

Transfusion of labile blood products (LBPs) generates occasional inflammatory : type, hazards; for a large part of these, no antigen/antibody conflict is thus, detected. Residual leucocytes used to account for a large part of such incidents - rarely accidents. Since, however, the systematic leukoreduction of LBPs, leucocytes are the less and less incriminated in adverse events. Platelets themselves proved capable of secreting copious amounts of inflammatory mediators, even in the absence of any deliberated stimulation. Meanwhile, even though exceptionally, inflammation can be observed after red blood cell transfusion. It has been noticed that the collection mode of cellular compounds, as well as the preparation and storage conditions are capable of inflicting lesions to the cell membranes and to activate those cells, and thus promoting inflammatory responses. Storage lesions as well as ageing of the stored cells alongside with cell apoptosis contribute to inflammatory responses. This present 'State of the Art' paper aims at encompassing the primary and secondary components of the LBPs, along with the various types of molecules displaying pro-inflammatory properties that can be encountered in transfusion. A better knowledge of causes of inflammatory transfusion-linked hazards is indeed instrumental to the implementation of safety measures aimed at reducing or suppressing these unwanted effects.

[Role of shedding in the activity of immunocompetent cells with reagin protection mechanism].

In work the data on studying of a parity of the maintenance of the soluble and membrane form of antigen CD23 at almost healthy faces is cited. To the specified sign 3 groups are allocated: in parallel low maintenance membrane and free CD23 (1 group), simultaneous increase of their concentration (2 group) and increase CD23 against significant decrease in concentration sCD23 (3 group). The conclusion becomes that photolytic shedding CD23 is made by the activated cells at increase in the maintenance of phenotypes of lymphocytes CD23+. Increase of expression CD23 by lymphocytes is associated with concentration increase of cytokines IL-6 and IFN-gamma, and a natural mitogen an alpha-fetoprotein. Abscission of cells CD23 and increase of concentration sCD23 occurs at excessive increase in maintenance IgE and anti-inflammatory ofcytokine IL-10. The parity of membrane and free forms CD23 is defined by activity of an expression, shedding and an educational level association.

Detection of reaginic antibodies against Faenia rectivirgula from the serum of horses affected with Recurrent Airway Obstruction by an in vitro bioassay.

Reaginic antibodies, mainly of the IgE and some IgG subclasses, play an important role in the induction of type I immediate hypersensitivity reactions. These antibodies bind through their Fc fragment to high affinity receptors (FcεRI) present in the membrane of mast cells and basophils. Previously, several studies have investigated the role of reaginic antibodies in the pathogenesis of RAO. However, whereas immunological aspects of RAO have been extensively studied, the precise sequence of events is still not well understood and role of IgE in this disease still remains controversial. Therefore, in this study a bioassay was developed for reaginic antibody determination in serum from RAO-affected horses in order to determine the etiology of disease. The technique involves measuring in vitro calcium mobilization in RBL-2H3 cells following incubation with horse serum from RAO-affected or unaffected horses and one of the RAO antigens (Faenia rectivirgula). Results demonstrated that 15% of samples from the RAO-affected horses reacted positively in this in vitro bioassay, whereas the samples from unaffected horses did not. This bioassay indicates that reaginic antibodies could be involved in the immunological mechanism leading to RAO; and this technique may facilitate future research in other allergic diseases in horses.

Effect of adverse storage conditions of antigen reagent on performance of the rapid plasma reagin test.

The aim of this study was to evaluate the performance of rapid plasma reagin (RPR) testing using expired and adversely stored antigen reagent. The sensitivity of RPR using antigen stored at 36 degrees C was compared at 3-monthly intervals with RPR using fresh antigen on 116 sera reactive by RPR and by Treponema pallidum particle agglutination (TPPA). After multiple phases of freezing and thawing, 8.3% of initial RPR reactive sera seroreverted. After storage at 36 degrees C for one year and 24 weeks after expiration the overall sensitivity of the adversely stored antigen was 93.8% compared with fresh antigen; the sensitivity was 100% for sera with RPR titres > or = 1:4 and 85.4% for sera with RPR titres of 1:1 and 1:2. The high stability of the reagent may increase the feasibility of the RPR test for use in poorly-equipped healthcare centres in developing countries.

Whole-blood hemagglutination inhibition test for venereal disease research laboratory (VDRL) antibodies.

Nontreponemal antibody tests such as the Venereal Disease Research Laboratory (VDRL) test are carried out on serum and widely used as screening tests for syphilis. The aim of the present study was to develop a screening test for syphilis making use of whole blood and VDRL liposomes. Antibody to human red blood cells was conjugated to VDRL liposomes and reacted with a diluted sample of patient whole blood. A total of 951 samples were tested by the new test and the VDRL tube test. All 49 VDRL samples positive by the VDRL test showed inhibition of hemagglutination in the whole-blood test (sensitivity, 100%). Of 902 samples with negative results by the VDRL test, 901 caused hemagglutination when tested with the liposomes (specificity, 99.9%). The hemagglutination inhibition method tests for syphilis in a simple one-step procedure in which whole blood is added to a tube containing liposomes. The new test has potential for point-of-care testing in developing countries.

[Reagin sensitizations and date of birth. Differences in function according to family history]. / Sensibilisations réaginiques et date de naissance. Différences en fonction des antécédents familiaux.

BACKGROUND: Atopy remains a hazy concept, as research in genetic markers is still not sufficiently elaborated due to multiple physiopathological mechanisms and mixing of patients. The aim of this work was to demonstrate this hypothesis by comparing birthdates according to family history and serum IgE to house dust mite and/or timothy grass pollen. PATIENTS AND METHODS: Rasts d1 and g6 were measured in the serum of 5,468 subjects, 2 to 18 years of age. The quotient of sensitizations to Dermatophagoides pteronyssinus and timothy grass pollen was established, month by month, according to family history. Representative curves were smoothed by computer. RESULTS: The circannual rhythm of quotients was remarkably similar within both groups of subjects with or without family history, with a time lag of 2 to 3 months. Subjects without family history were born 2 to 3 months before subjects with family history, i.e., they were 2 to 3 months older at the time of antigenic stimulation. CONCLUSIONS: Mechanisms by which subjects have been sensitized, still unknown, happen in different times according to family history. These findings suggest several genetic factors.

Nonimmune hydrops fetalis due to congenital syphilis associated with negative intrapartum maternal serology screening.

We present an unusual case, in which a woman presenting with markedly decreased fetal movements at 29 weeks gestation following a recent increase in fundal height was noted sonographically to have fetal hydrops consisting of scalp edema, marked hepatomegaly, ascites, and polyhydramnios. No lethal structural congenital anomaly was noted. Admission laboratory examinations revealed a negative antibody screen and a negative RPR. Emergent cesarean section was performed due to prolonged fetal bradycardia during biophysical profile testing. The acidotic hydropic neonate weighing 1825 g was resuscitated yet succumbed at 3 hr of life following intravenous administration of antibiotics. Neonatal blood was RPR positive at 1:16. Postmortem pathology examination demonstrated severe multiorgan system failure secondary to overwhelming congenital syphilis. Extensive extramedullary hematopoiesis was noted and histopathology with Dieterle stains revealed numerous hepatic spirochetes. Postpartum reexamination of the maternal blood with serial dilutions revealed a positive RPR at 1:1024. This case emphasizes that initial negative screening for syphilis may be seen despite overwhelming infection, a condition that has been termed the "prozone effect."

Chemical denaturation of ovalbumin abrogates the induction of oral tolerance of mouse reaginic antibody responses.

The effect of chemical denaturation of ovalbumin (OVA) on the induction of oral tolerance of reaginic antibody responses was studied. Both urea-denatured OVA (UD-OVA) and carboxymethylated UD-OVA (CM-OVA) were purified by centrifugation. When compared with OVA and UD-OVA, CM-OVA had the least sensitizing capacity and allergenicity in IgE responses to OVA. BALB/c IgE, IgG1 and IgG antibody responses were suppressed by OVA, but not by UD-OVA or CM-OVA, fed prior to sensitization with OVA, UD-OVA, or CM-OVA in alum, respectively. The priming effect of specific IgG and IgG1 antibody responses was induced by CM-OVA fed prior to sensitization with OVA or CM-OVA. The proliferation of BALB/c spleen cells and their secretion of T helper type 2 (Th2) cytokines interleukin-4 (IL-4) and IL-5 were also orally tolerized by OVA, but not by denatured OVA. Although denatured OVA is hypoallergenic, the present result indicates that denaturation of a soluble protein prevents the induction of oral tolerance of Th2 responses.

[Allergy to cow's milk]. / L'allergie au lait de vache.

After recalling the medical reluctance as well as the risks that there are in complete elimination of milk in infants, the author presents several clinical pictures and then a classification of the immunological types. Allergic shock of neonates, digestive and extra-digestive (skin and respiratory airways) symptoms finally the rare chronic gastro-enteritis to cow milk. Non-reaginic food allergies: Acute gastro-enteropathy to cow milk, with villous atrophy and Heiner's syndrome, delayed hypersensitivities are studied, of difficult diagnosis that may cover almost all pathologies. They may be found in the digestive system, respiratory, the kidneys and even in the organs of behaviour. Migrane of food origin must be remembered. Development in regressive rules is a function of the type of allergy and the suddenness of the symptoms. Diagnosis is above all by questioning and confirmation or not by skin and in vitro tests. Certainty can only be shown by tests of elimination and re-introduction. The diet, at the same time of both diagnostic and therapeutic value, is based on the replacement of cow milk by foods that contain the same amount of proteins. It is essential, especially in the very small, to have perfect match of food so as to avoid any risk of a dramatic hypoprotinemia, which may happen if the child does not like the suggested diet, or if the parents cannot buy the substitution products. In such conditions great care must be taken to avoid provoking a crisis. Care must be taken to decide: If the elimination of cow milk is always justified each time. If it is, always check that the substituted protein is properly made, the family may change the diet mistakenly. It is better, finally, to keep the eczema, rather than die with it healed.

[Risk indicators of reaginic allergy: relations between atopic dermatitis and serum specific IgE of various pneumallergens]. / Les indicateurs de risque de l'allergie réaginique: relations entre dermatite atopique et IgE sériques spécifiques de divers pneumallergènes.

This study was conducted in 1,091 children and adolescents submitted to an allergy check-up for respiratory symptoms. All subjects had a research of IgE for Dermatophagoides pteronyssinus, cat and timothy grass pollen by CAP-System Pharmacia. Three hundred subjects had a personal history of atopic dermatitis. They were compared to the 791 others. No difference was found for age, sex, family history of allergic respiratory disease, breast feeding nor exposure to tobacco smoke. The IgE level was significantly enhanced among subjects with an history of atopic dermatitis, but this difference was due to a higher frequency of sensitisations. In subjects with at least one positive RAST (> 0.35 kIU/l) no significant difference was found (p = 0.41). The highest frequency of sensitisations in case of atopic dermatitis was exclusively related to the simultaneous sensitisation against all the three allergens. Such situation was more frequent when the atopic dermatitis was noted before the age of six months. On the other hand, the sensitisation severity, according to RASTs' classes, was independent of atopic dermatitis history. The author points out the necessity of strong primary preventive measures of pneumallergen environmental avoidance for all infants with atopic dermatitis.

Rapid plasma reagin card test: evaluation of a hand-rotation procedure and stability of the RPR antigen.

Reported are the results of a comparative study of two procedures for the rapid plasma reagin (RPR) test for syphilis serology: in one approach a mechanical rotator was used and in the other, hand rotation was employed. Both procedures were performed on 327 sera. The agreement between both was 98.8%. Three sera that exhibited minimal reactivity (titre = 1) in the mechanical-rotation RPR were nonreactive in the hand-rotation RPR. RPR antigen was stored for 3 months at room temperature (mean, 21 degrees C) and 30 degrees C. There was no difference in the reactivity of 62 sera (50 positive, 12 negative) that were tested using either adversely stored antigens or antigen stored at 4 degrees C. In poorly equipped settings at the primary health care level, the hand-rotation RPR is a practical alternative to mechanical rotation. Also, the stability of the antigen under adverse storage conditions is an additional advantage of RPR for use in tropical areas.

Presence of anti-insulin reaginic auto-antibodies of the IgG4 class in insulin-dependent (type I) diabetic patients before insulin therapy.

The autoimmune aetiology of type I diabetes has been well documented. We studied whether anti-insulin anaphylactic antibodies were present on the membrane of basophils from type I diabetics by the toluidine blue method (detecting basophil activation after stimulation by insulin). We observed that basophils of recently diagnosed insulin-dependent diabetic patients (n = 13) were statistically more frequently activated by insulin than basophils from noninsulin-dependent diabetics (p < 0.002, n = 8) or non-diabetic subjects (p < 0.05, n = 9). Basophils from normal donors were passively sensitized with plasma from insulin-dependent diabetics and could then be activated by insulin. This sensitization still occurred when using plasma previously heated to 56 degrees C, indicating that the sensitizing antibodies were not of the IgE class. When basophils from type I diabetics were preincubated with anti-IgG subclasses, only anti-IgG4 monoclonal antibodies inhibited the insulin-induced basophil activation. By contrast, preincubation with blocking concentrations of anti-IgG1-3 antibodies or desensitization of the IgE pathway did not modify basophil activation. These experiments strongly suggest the presence of anti-insulin antibodies of the IgG4 subclass in insulin-dependent diabetics before any insulin administration and provide a simple tool to complement the usual method of detecting auto-antibodies in diabetes.

Effects of rheumatoid factor, antinuclear antibodies and plasma reagin on the serologic assay for Lyme disease.

Rheumatoid factor (RF), antinuclear antibodies (ANA) and the presence of other spirochetal infections have been reported to be the source of false positive serologic tests of Lyme disease. To evaluate this, we studied their effect upon the Lyme assay in use in our clinical laboratory. Of 64 rapid plasma reagin (RPR) test positive sera, 2 had positive Lyme antibody tests, not statistically different than controls. Of 43 RF positive sera, 2 had positive lyme tests, no different than controls, and 1 of 53 ANA containing sera had positive Lyme tests, again, not different from controls. There was no relationship of titer of RPR or ANA with Lyme results, nor of ANA pattern. Sera containing high titer RF, however, had slight interference, producing an increase in equivocal Lyme assay results. From the other point of view, sera that were Lyme test positive had no increased frequency of RPR or RF, but had an increased frequency of ANA. Therefore, neither RPR, RF or ANA were found to markedly interfere with the Lyme assay. However, Lyme antibodies may interfere with the ANA test.