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Delia Colombo,1 Sergio Chimenti,2 Paolo Antonio Grossi,3 Antonio Marchesoni,4 Federico Bardazzi,5 Fabio Ayala,6 Lucia Simoni,7 Donatella Vassellatti,1 Gilberto Bellia1 On behalf of SYNERGY Study Group 1Novartis Farma Italia, Origgio (VA), 2Tor Vergata Polyclinic Rome, 3Macchi Hospital and Foundation, Varese, 4Orthopaedic Institute Pini, Milan, 5S Orsola-Malpighi Polyclinic, Bologna, 6University Federico II Naples, 7MediData srl, Modena, Italy Background: Sex medicine studies have shown that there are sex differences with regard to disease characteristics in immune-mediated inflammatory diseases, including psoriasis, in immune response and susceptibility to viral infections. We performed a post hoc analysis of the Observational Study of infectious events in psoriasis complicated by active psoriatic arthritis (SYNERGY) study in patients with psoriatic arthritis (PsA) treated with immunosuppressive regimens including cyclosporine, in order to evaluate potential between-sex differences in severity of disease and prevalence of viral infections.Methods: SYNERGY was an observational study conducted in 24 Italian dermatology clinics, which included 238 consecutively enrolled patients with PsA, under treatment with immunosuppressant regimens including cyclosporin A. In this post hoc analysis, patients' demographical data and clinical characteristics of psoriasis, severity and activity of PsA, prevalence of seropositivity for at least one viral infection, and treatments administered for PsA and infections were compared between sexes.Results: A total of 225 patients were evaluated in this post hoc analysis, and 121 (54%) were males. Demographic characteristics and concomitant diseases were comparable between sexes. Statistically significant sex differences were observed at baseline in Psoriasis Area and Severity Index score (higher in males), mean number of painful joints, Bath Ankylosing Spondylitis Disease Activity Index, and the global activity of disease assessed by patients (all higher in females). The percentage of patients with at least one seropositivity detected at baseline, indicative of concomitant or former viral infection, was significantly higher among women than among men. No between-sex differences were detected in other measures, at other time points, and in treatments. Patients developed no hepatitis B virus or hepatitis C virus reactivation during cyclosporine treatment.Conclusion: Our post hoc sex analysis suggests that women with PsA have a greater articular involvement and a higher activity of disease compared to males. Immunosuppressive treatment with cyclosporine seems not to increase susceptibility to new infections or infectious reactivations, with no sex differences. Keywords: psoriatic arthritis, sex, viral infections, SYNERGY, cyclosporine

Delia Colombo,1 Gilberto Bellia,1 Donatella Vassellatti,1 Emanuela Zagni,1 Simona Sgarbi,2 Sara Rizzoli21Novartis Farma, Origgio, 2MediData, Modena, ltaly Abstract: Only recently has medical research begun to understand the importance of taking sex into account, recognizing that symptoms and responses to medical treatment may be very different between males and females. However, the analyses provided by the pharmaceutical industry to regulatory authorities often do not present safety and efficacy data by sex. Novartis has started a gender-medicine project called MetaGeM, which includes nine observational studies sponsored by Novartis Farma, Italy; conducted in Italy between 2002 and 2013 in a range of different clinical areas. The MetaGeM project aims to analyze and describe by means of post hoc analyses and meta-analyses, clinical outcomes, therapeutic approaches, and safety data of these studies, by sex: PSYCHAE; GENDER ATTENTION in psoriasis; Synergy in psoriatic arthritis; ICEBERG in HBsAg carriers; SURF and CETRA in liver- and renal transplanted patients, respectively; DEEP in Parkinson's disease; and EVOLUTION and AXEPT in Alzheimer's disease. The present paper describes the methodology of the MetaGeM project.Keywords: gender-medicine, MetaGeM project, methodology

The behaviour of some immunologic parameters was studied in order to explain the presence or the lack of symptomatology in subjects with IgE specific to foods. In particular, we compared the levels of serum and salivary IgA and IgE antibody specific to apple in 33 patients allergic to birch and with anti-apple IgE, of whom 24 had oral allergy syndrome after eating apple and nine were apple tolerants. We found no differences in the IgE-related parameters such as levels of anti-apple IgE antibody in serum and secretions, mean size of apple skin prick test, and number of patients with a positive histamine release from peripheral basophils stimulated by apple. Similarly, we detected no statistically significant differences in serum and salivary total IgG and total anti-apple IgA antibody of the two groups. We could, however, observe a significantly higher anti-apple salivary IgA/anti-apple serum IgE and anti-apple salivary IgA/anti-apple serum IgA ratios and a significant correlation between the same parameters in tolerant patients when compared with the intolerants. These results seem to suggest that the presence of appropriate levels of secretory anti-apple IgA associated to anti-apple IgE might be one of the factors playing a key role in the prevention of clinical symptoms in atopic subjects.

Most of the controlled trials of specific immunotherapy (SIT) with house dust mite showed a good clinical efficacy of different kinds of extract after variable periods of treatment. However, few of them looked at all the parameters available to monitor this therapy, such as threshold dose of specific provocation test, end point titration and immunological variations. In particular, the behaviour of specific IgE antibodies is not completely known, while, in more recent studies, mite specific IgG antibodies have been shown to increase even in the early stages of treatment. Few data are available on mite specific IgG1-4 subclasses. The preliminary results of a double blind placebo controlled trial we performed with alginate conjugated Dermatophagoides pteronyssinus extract seem to indicate a good clinical and immunological response to this kind of extract. Moreover, we observed a significant increase of specific IgG antibodies, total and subclasses IgG1.2.4, with a prevalence of IgG4 subclass after three months of SIT. After two years of SIT mite specific IgG1 antibodies showed a tendency to decrease, while IgG4 antibodies maintained a constantly high level.

Venom immunotherapy provides clinical protection against hymenoptera stings in almost all treated allergic patients. Venom specific IgG antibodies often rise during immunotherapy and some studies found an association between their levels and clinical protection in subjects treated with Yellow Jacket venom. It is interesting to report that, among IgG subclasses, venom specific IgG4 show the most significant increase but IgG1 could represent a relevant immunological mechanism, exerting a regulatory function on venom specific IgE levels. We observed in patients submitted to Honey Bee venom immunotherapy a significant increase of venom specific IgG1 and IgG4 antibodies, while IgG2 showed an insignificant increase only in some patients. Persistent high levels of IgG4 with respect to decreasing levels of IgG1 were observed only after prolonged treatment.