Fabrizio Guarneri

Helicobacter pylori and autoimmune pancreatitis: role of carbonic anhydrase via molecular mimicry?

Autoimmune pancreatitis is a recently defined nosological entity, which accounts for 4.6‐6% of all forms of chronic pancreatitis and is often associated with other autoimmune diseases, particularly Sjögrens syndrome. Possession of the HLA DRB1*0405‐DQB1*0401 genotype confers a risk for the development of autoimmune pancreatitis. Autoantibodies against carbonic anhydrase II and lactoferrin are frequently present in affected subjects and are suspected to have a pathogenic role. A link between gastric infection by Helicobacter pylori and autoimmune pancreatitis has been hypothesized. We used in silico protein analysis and search for HLA binding motifs to verify this hypothesis. We found a significant homology between human carbonic anhydrase II and α‐carbonic anhydrase of Helicobacter pylori, an enzyme which is fundamental for the survival and proliferation of the bacterium in the gastric environment. Moreover, the homologous segments contain the binding motif of the HLA molecule DRB1*0405. Our data strengthen the hypothesis that gastric Helicobacter pylori infection can trigger autoimmune pancreatitis in genetically predisposed subjects.

Recombinant human erythropoietin influences revascularization and healing in a rat model of random ischaemic flaps.

In order to ascertain whether erythropoietin plays a role in early and late repair processes following ischaemic skin flap injury, a dorsal, caudally based skin flap was created in rats. The rats were successively divided into four groups. Group 1 was not treated. The other groups were treated with a subcutaneous administration of 0.9% NaCl saline solution (group 2), a subcutaneous administration of vehicle (group 3) or a subcutaneous administration of 300 IU/kg/day of recombinant human erythropoietin (group 4). We evaluated the possible relationships between neutrophil accumulation, myeloperoxidase activity and content in flap tissue, flap survival, flap temperature (using telethermography) and flap revascularization (using videocapillaroscopy). Necrosis in the flap was significantly less extensive in group 4 than in groups 1, 2 and 3. A significant increase in neutrophil infiltration occurred between the 1st and 24th hour in these groups, but this was not observed in group 4. These findings were confirmed by biochemical data of myeloperoxidase activity and malonyldialdehyde content. Between the 1st and 7th days, we recorded an increase of about 20% in flap temperature in groups 1, 2 and 3, whereas no significant variation was observed in group 4. On the 7th day, videocapillaroscopic findings showed an increase in the mean vascularization index in group 4. Our findings suggest that recombinant human erythropoietin administration can improve the wound healing process, in both early and late stages of injury, by reducing inflammatory response, increasing the density of capillaries in ischaemic flaps and allowing earlier repair of a damaged area.

Treatment of Psoriatic Nails with Topical Cyclosporin: A Prospective, Randomized Placebo-Controlled Study

Background: Nail involvement is a frequent event in the course of psoriasis causing severe distress. While systemic cyclosporin (CsA) represents a well-established therapy of psoriasis, its topical use is limited by the difficult penetration of the molecule through the skin and the nail because of its highly lipophilic nature. Objectives: We carried out a prospective randomized placebo-controlled study in order to analyze the effectiveness and tolerability of topical oil-dissolved 70% CsA solution in nail psoriasis. Methods: Sixteen adult patients with nail psoriasis, divided randomly into two groups of 8 patients (group A and group B), were treated respectively with a 70% maize-oil-dissolved oral CsA solution and maize oil alone. To compare the therapeutic effectiveness, all patients were evaluated, before starting the treatment and after 12 weeks of therapy, by the same dermatologists. The patients were also asked to assess the severity of their nail involvement at baseline and at the end of the treatment. Results: In group A, 3 patients came to a complete resolution of nail lesions and 5 showed a substantial improvement of the overall severity score. In group B, a slight improvement was noted in only 1 patient. All the patients of group A judged positively the results of the therapy, while in group B only 1 patient reported a moderate improvement. Conclusion: Our results show that topical therapy with oral CsA solution is a safe, effective and cosmetically highly acceptable treatment modality for nail psoriasis. The ability of CsA to influence keratinocyte proliferation and T-cell lymphokine release, reducing the cornification of the upper layers of the epidermis, may prevent the typical alterations observed in nail psoriasis.

Environmental factors and genetic background that interact to cause autoimmune thyroid disease.

Purpose of reviewTo provide an updated list of genetic and environmental causative factors of autoimmune thyroid disease, and report about the recent discoveries concerning their interaction in the pathogenesis of thyroid autoimmunity. Recent findingsAlthough significant discoveries have been made on genetic and environmental factors underlying the development of autoimmune thyroid disease, few data are available about the mechanisms by which they interact. The most interesting news in this field comes from research on molecular mimicry between microbial antigens and thyroid autoantigens. The molecular mimicry model postulates that, in predisposed subjects, a microbial antigen could trigger autoimmunity because of its structural similarity to an autoantigen of the host, and is a paradigmatic example of the multifactorial interaction of several genes and environmental factors to cause autoimmune diseases, including thyroid diseases. SummaryRecent findings help us to better understand the functional mechanisms of the immune system, which are still only partially known. Beyond the scientific interest, this knowledge has immediate repercussions on clinical practice because it can suggest possible therapeutic targets for new treatments, as well as better and more specific uses of currently available drugs and resources.

Correlation between endocrinological parameters and acne severity in adult women.

Many studies demonstrate increased androgen levels and high prevalence of polycystic ovaries in women affected by acne. We evaluated the relationship between clinical features, ultrasonographic data on polycystic ovaries and hormonal parameters in 129 women >17 years of age with acne. Serum levels of androgens of ovarian and adrenal origin were measured. Menstrual cycle regularity, hirsutism, body mass index and ultrasonographic evaluation of ovaries were recorded. Raised levels of at least one androgen were evident in a majority of our patients. Only 19% of them had polycystic ovary syndrome. Hirsutism and acne severity correlated negatively with serum sex hormone-binding globulin (SHBG) levels (p<0.05). No correlation between acne severity and hirsutism was found. In post-pubertal women, severity of acne seems to depend on peripheral hyperandrogenism, with a negative relationship between the acne severity and serum SHBG levels. We strongly recommend the evaluation of serum SHBG levels in women with acne in order to select patients who can have a better response to appropriate hormonal regimes.

Identification of potentially cross-reactive peanut-lupine proteins by computer-assisted search for amino acid sequence homology.

Background: Allergic cross-reactions are an issue of major concern because of implications for public health. The molecular basis of cross-allergy is the similarity of epitopes belonging to proteins of different organisms. Lupine is an emerging cause of food allergy, which has become a ‘hot topic’ because of recent large-scale introduction into processed foods and frequent cross-reactions with other members of the legume family. However, no lupine allergen has been characterized thus far. Prompted by a recently reported case of peanut-lupine cross-allergy, we wished to identify the possible cross-reactive allergen(s) between the two vegetal species. Methods: We used computer-aided amino acid sequence comparison, a well-established technique for the study of protein homology, and followed the FAO/WHO guidelines for the identification of potential allergens. We also performed a three-dimensional modeling of the suspected cross-reactive proteins to compare their molecular surfaces. Results: We found a highly significant sequence homology and molecular similarity between allergen Ara h 8 of peanut and pathogenesis-related protein PR-10 of white lupine. Another protein of lupine, the β-conglutin precursor, was found to be significantly homologous to the Ara h 1 allergen of peanut. The molecular surfaces of Ara h 8 and PR-10 were remarkably similar. Conclusions: Our in silico data allow to predict the allergenicity of PR-10 and β-conglutin precursor of white lupine according to FAO/WHO guidelines. Amino acid sequence homology also suggests that these proteins could be responsible, at least in part, for some of the allergic cross-reactions between peanut and lupine reported in the literature.

Cross‐reactivity of Anisakis simplex: possible role of Ani s 2 and Ani s 3

Background  Anisakis simplex is a fish parasite that can cause allergy in humans. The multiple cross‐reactivities of this nematode make diagnostic tests for allergy unreliable, because of frequent false‐positive results. To date, only four allergens of A. simplex have been characterized, but their role in cross‐reactivity is largely unknown.

Protein contact dermatitis and allergic asthma caused by Anisakis simplex

Anisakis simplex is a nematode that is a parasite of several marine organisms during its life cycle. It is known in human medicine as an accidental gastrointestinal parasite in subjects who had ingested raw fish. Since the late 1990s, several reports have suggested that Anisakis simplex can also cause allergic reactions in subjects who frequently eat or manipulate parasitized fish. Allergy can be particularly common and severe where there has been contact with the parasite from occupational exposure; some authors have suggested that such reactions should be classified as an occupational disease in fishermen and fishmongers (1). We report an unusual case of simultaneous type I and type IV allergic reaction (asthma and contact dermatitis) because of occupational contact with fish parasitized by Anisakis simplex.

Treatment with omalizumab in a 16‐year‐old Caucasian girl with refractory solar urticaria

Based on recent evidence, including our results, we believe that the usefulness of the sIgE/total IgE ratio to predict tolerance to food allergens needs to be revisited in larger studies which can control for factors potentially influencing the results. In conclusion, in this cohort, the diagnostic performance of the OVA-sIgE/total IgE ratio was superior to sIgE or SPT to EW, OVA or OVM alone in predicting raw egg tolerance development in school-aged children and teenagers with IgE-mediated egg allergy. Acknowledgments The authors would like to thank Dr Paul Turner, MRC Clinician Scientist at Imperial College London, for his valuable comments on this letter.

Topical botanically derived products: use, skin reactions, and usefulness of patch tests. A multicentre Italian study

The evidence on the safety of topical preparations containing botanical extracts is limited.