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2.
J Eur Acad Dermatol Venereol ; 32(12): 2074-2082, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30288799

ABSTRACT

BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin disease in both adults and children. Whilst topical calcineurin inhibitors (TCIs), tacrolimus ointment and pimecrolimus cream, have proven efficacy for the treatment of AD, it is important to involve experts to obtain their opinion on its optimal treatment. OBJECTIVE: Using a modified Delphi approach, this project aimed to generate consensus amongst experts on the use of TCIs in the treatment of AD, with a focus on the differentiation between tacrolimus and pimecrolimus. METHODS: Six expert dermatologists from different European countries participated in this project based on their experience with AD and its treatment, which was evaluated by literature analysis and expert opinion. Consensus amongst the experts was generated using a modified Delphi approach, consisting of three distinct phases, during which a web meeting (June 2017), two online rounds of blinded Delphi voting (July-September 2017) and a face-to-face meeting (November 2017) were conducted. The consensus statements concerned two main topics: (i) Background of AD; and (ii) TCIs in AD. Hot topics in the treatment of AD not supported by meta-analysis, clinical trials or large observational studies were also discussed based on clinical experience. RESULTS: In total, 25 consensus statements were defined and validated: eight statements on the general background of AD and 17 statements on the use of TCIs in AD, including their mechanism of action and therapeutic indications in AD, efficacy in adult and paediatric AD patients, pharmacokinetics, incidence of adverse events and safety concerns. Hot topics on the use of TCIs for the treatment of AD included cream vs. ointment, dosages, TCIs contact allergy, burning sensation management, superinfection and vaccination concerns. CONCLUSION: Topical calcineurin inhibitors are a suitable therapy for AD, and selection of the specific TCI should be based on factors which differentiate tacrolimus from pimecrolimus.


Subject(s)
Calcineurin Inhibitors/pharmacology , Dermatitis, Atopic/drug therapy , Tacrolimus/analogs & derivatives , Tacrolimus/pharmacology , Calcineurin Inhibitors/therapeutic use , Consensus , Delphi Technique , Humans , Tacrolimus/therapeutic use
3.
J Biol Regul Homeost Agents ; 29(3): 547-61, 2015.
Article in English | MEDLINE | ID: mdl-26403393

ABSTRACT

Psoriatic arthritis is an inflammatory seronegative spondyloarthropathy that occurs in approximately 25% of patients with psoriasis and is a progressive and severely disabling disease. Most patients have had psoriasis for several years before the development of arthritis or develop the joint and skin condition simultaneously. Given the absence of specific diagnostic test for psoriatic arthritis, clinical findings remain the standard criteria for the diagnosis. Patients with psoriasis presenting to the dermatologist for management of their skin disease may have joint symptoms related or not to psoriatic arthritis and similarly arthritic patients presenting to a rheumatologist for the management of psoriatic arthritis may have skin lesions related or not to psoriasis. In this paper an expert panel of specialist belonging to the “Associazione Dermatologi Ospedalieri Italiani” (ADOI) and “Collegio dei Reumatologi Ospedalieri Italiani” (CROI) analysed the international literature and scientific recommendations and also investigated the Italian setting. It has been demonstrated in the literature that a multidisciplinary clinical setting may benefit patients with psoriatic arthritis from both diagnostic and therapeutic points of view. The comparative analysis of the Italian clinical records used by ADOI and CROI have highlighted some substantial differences. Collaboration between the dermatologist and rheumatologist allows for a more complete appreciation of the overall skin and musculoskeletal disease burden, and subsequently leads to a more comprehensive treatment approach.


Subject(s)
Arthritis, Psoriatic/therapy , Dermatology , Practice Patterns, Physicians' , Rheumatology , Humans
4.
Allergy ; 70(8): 933-43, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25903791

ABSTRACT

BACKGROUND: Nonspecific lipid transfer proteins (nsLTPs) represent a major cause of systemic food allergic reactions in the Mediterranean area. This study investigate hierarchical patterns and cluster relationships of IgE sensitization to different nsLTPs, and the relationship to clinical allergy in a large Italian cohort. METHODS: A total of 568 nsLTP-positive subjects after IgE ImmunoCAP-ISAC microarray analysis with Ara h 9, Art v 3, Cor a 8, Jug r 3, Pla a 3, Pru p 3 and Tri a 14 allergens were studied. IgE inhibition experiments were carried out with mugwort and plane tree pollen extracts. RESULTS: Eighty-two per cent of nsLTP-positive participants (94% if <6 years old) were Pru p 3(pos) , and 71% were Jug r 3(pos) . Participants who reacted to >5 nsLTPs reported a higher incidence of food-induced systemic reactions. Only Art v 3 and Pla a 3 (mugwort and plane tree nsLTPs, respectively) were associated with respiratory symptoms, and a correlation was observed between sensitization to pollen and plant food nsLTPs, particularly between Pla a 3 and tree nut/peanut nsLTPs. Co-sensitization to Par j 2 and PR-10 or profilin pan-allergens was associated with a lower prior prevalence of severe food-induced reactions. In inhibition assays, plane and mugwort pollen extracts inhibited 50-100% of IgE binding to food nsLTPs in microarrays. CONCLUSIONS: Testing IgE reactivity to a panel of nsLTP allergens unveils important associations between nsLTP sensitization profiles and clinical presentation and allows the identification of novel cluster patterns indicating likely cross-reactivities and highlighting potential allergens for nsLTP immunotherapy.


Subject(s)
Carrier Proteins/immunology , Food Hypersensitivity/immunology , Food Hypersensitivity/therapy , Immunization/methods , Adolescent , Adult , Aged , Allergens/immunology , Child , Child, Preschool , Cluster Analysis , Cohort Studies , Female , Food Hypersensitivity/physiopathology , Humans , Hypersensitivity/epidemiology , Hypersensitivity/immunology , Hypersensitivity/therapy , Immunoglobulin E/immunology , Italy/epidemiology , Male , Middle Aged , Pollen/immunology , Prevalence , Risk Assessment , Severity of Illness Index , Young Adult
5.
G Ital Dermatol Venereol ; 150(4): 449-59, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25747260

ABSTRACT

CT-P13, a biosimilar of infliximab, was the first biosimilar monoclonal antibody to be approved in both the European Union and Korea. As a monoclonal antibody, CT-P13 is a large molecule with a high molecular weight, and as such it differs from other biosimilars currently in the market. The comparability exercise for CT-P13, therefore, requires special consideration, as it was the first demonstration of biosimilarity between a biosimilar monoclonal antibody and its originator. This paper summarizes current regulations on the approval of biosimilars, describes the evidence leading to the approval of CT-P13, and discusses the potential role of this molecule in the Italian scenario on the basis of the view of a group of experts.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Biosimilar Pharmaceuticals/therapeutic use , Infliximab/therapeutic use , Antibodies, Monoclonal/chemistry , Biosimilar Pharmaceuticals/chemistry , Drug Approval , Humans , Infliximab/chemistry , Italy , Molecular Weight
6.
Br J Dermatol ; 172(1): 187-95, 2015 Jan.
Article in English | MEDLINE | ID: mdl-24974982

ABSTRACT

BACKGROUND: Data on the epidemiological impact and clinical characteristics of chronic hand eczema in Southern Europe are lacking. OBJECTIVES: To estimate the prevalence of chronic hand eczema in its different stages of severity and refractoriness to standard therapy in patients accessing Italian dermatological reference centres, and to evaluate sociodemographic and clinical factors associated with each stage. METHODS: A cross-sectional multicentre study was conducted. Adult patients with hand eczema, consecutively accessing 14 centres over a 6-month period, were enrolled. Patients were classified according to disease duration, severity and response to standard therapy with potent topical corticosteroids. Logistical regression was performed to investigate the relationship between sociodemographic and clinical data with different stages of eczema. RESULTS: The total number of participants was 981. Hand eczema was chronic in 83·5% of patients; 21·3% had severe eczema, with 62·0% of these patients refractory to standard therapy. Food processing and related work, the health professions, craft and related trade works (building, plumbing, electrical), hairdressing/beauty and handicraft work were most frequently associated with chronic hand eczema. Severe chronic hand eczema was more likely to be seen in men, older patients and those with less education. Severe and refractory hand eczema was also more likely among the unemployed and patients with allergic rhinitis and/or atopic dermatitis. CONCLUSIONS: Chronic hand eczema is frequent among patients with hand eczema accessing dermatology centres. Many patients were severe and refractory to standard therapy. The appropriate identification of hand eczema is the first step in implementing effective and efficient treatments.


Subject(s)
Eczema/epidemiology , Hand Dermatoses/epidemiology , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Chronic Disease , Cross-Sectional Studies , Dermatitis, Occupational/epidemiology , Dermatitis, Occupational/therapy , Eczema/therapy , Female , Hand Dermatoses/therapy , Humans , Italy/epidemiology , Male , Middle Aged , Prevalence , Sex Distribution , Socioeconomic Factors , Young Adult
7.
Br J Dermatol ; 168(1): 80-4, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22913489

ABSTRACT

BACKGROUND: Epidermolysis bullosa acquisita (EBA) is a rare autoimmune mucocutaneous bullous disease caused by autoantibodies against type VII collagen, a component of anchoring fibrils that stabilizes dermoepidermal adherence. Type VII collagen is composed of a collagenous domain linked by the noncollagenous (NC)1 and NC2 domains. OBJECTIVES: To assess the repeatability, sensitivity and specificity of a recently developed enzyme-linked immunosorbent assay (ELISA) for detection of anti-type VII collagen autoantibodies, and to ascertain whether they may be a marker of disease activity in EBA. METHODS: Using this ELISA, which was able to recognize autoantibodies against the NC1 and NC2 epitopes of type VII collagen, we tested 14 EBA sera, 30 healthy control sera and 113 disease control sera. RESULTS: In the EBA sera group, 12 out of the 14 samples were positive in ELISA, with autoantibody titres varying from 7·2 to 127·9UmL(-1) (cutoff value <6), the sensitivity of the method being 86%. Among the controls, only two bullous pemphigoid sera tested positive, the specificity being 98·6%. A good correlation was found between EBA disease severity, expressed as autoimmune bullous skin disorder intensity score, and the serum levels of anti-collagen VII autoantibodies, measured by ELISA (n =14; r=0·965; P=0·0001). The intra- and interassay coefficients of variation of the ELISA method ranged from 6·3% to 18·3%. CONCLUSIONS: This NC1+NC2 ELISA can be a practical assay for the diagnosis of EBA. The correlation between autoantibody titres and disease severity suggests its usefulness as a marker of disease activity in EBA However, this should be confirmed by studies on larger series of patients.


Subject(s)
Autoantibodies/blood , Collagen Type VII/immunology , Epidermolysis Bullosa Acquisita/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Enzyme-Linked Immunosorbent Assay/methods , Female , Fluorescent Antibody Technique, Indirect/methods , Humans , Immunoblotting/methods , Italy , Male , Middle Aged , Rare Diseases/diagnosis , Sensitivity and Specificity
8.
G Ital Dermatol Venereol ; 147(6): 609-24, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23149707

ABSTRACT

Calcipotriol, a vitamin D analogue, and betamethasone dipropionate, a high potency corticosteroid, are complementary agents for the topical treatment of psoriasis vulgaris. Robust evidence on the efficacy and safety of their fixed combination has been provided by randomized, double-blind, controlled clinical trials involving more than 7000 patients with the ointment formulation in psoriasis of the body and more than 4000 patients with the gel formulation in scalp psoriasis. These trials have shown that the fixed combination ointment is more effective and better tolerated, not only than placebo, but also than calcipotriol and tacalcitol monotherapies. In addition, it has proved, in most instances, to be more effective than betamethasone and at least as well tolerated. The same applies to the gel for scalp and body psoriasis. Safety studies have excluded that repeated courses of treatment with the fixed combination for up to one year produce systemic effects. Studies have also shown that the fixed combination treatment improves quality of life to a significantly greater extent than calcipotriol, with the once daily regimen most appreciated by patients, in both active disease and recurrency. Because of the extensive evidence, American and European guidelines recommend the calcipotriol/betamethasone dipropionate fixed combination as first line topical treatment for mild to moderate plaque psoriasis of the body and scalp.


Subject(s)
Anti-Inflammatory Agents/administration & dosage , Betamethasone/analogs & derivatives , Calcitriol/analogs & derivatives , Dermatologic Agents/administration & dosage , Psoriasis/drug therapy , Anti-Inflammatory Agents/adverse effects , Betamethasone/administration & dosage , Betamethasone/adverse effects , Calcitriol/administration & dosage , Calcitriol/adverse effects , Dermatologic Agents/adverse effects , Drug Therapy, Combination , Gels , Humans , Quality of Life , Scalp Dermatoses/drug therapy , Time Factors
9.
Int J Immunopathol Pharmacol ; 24(1): 185-8, 2011.
Article in English | MEDLINE | ID: mdl-21496401

ABSTRACT

Toll-like receptors (TLRs) are a key part of the innate immune system that detect pathogen-associated molecular patterns (PAMPs) of microorganisms and their stimulation results in the activation of signaling pathways leading to the modulation of inflammatory and immune responses. Since psoriasis is a complex, inflammatory and immune skin disease, characterized by an abnormal immune response and increased proliferation of keratinocytes, with an increased production of proinflammatory cytokines, TLRs could play an important role in the pathogenesis of the disease. We propose to assess the modulation of TLR expression on psoriatic skin of patients treated with Adalimumab and systemic conventional therapies. We therefore recruited fifteen patients: ten were treated with adalimumab and five with systemic conventional therapies; their clinical conditions were analyzed by PASI index and skin biopsies were evaluated for TLR1 and TLR2 expression by immunohistochemistry assays. Our data suggest adalimumab is not only able to improve the clinical condition of psoriatic patients, but also to modulate TLR1 and TLR2 expression involved in psoriasis, as in healthy skin. Adalimumab is a most promising biological drug able to orchestrate immune and inflammatory responses in psoriatic lesions, recovering TLR expression on basal keratinocytes and improving clinical conditions of psoriatic patients, with no evident side effects.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antibodies, Monoclonal/therapeutic use , Psoriasis/drug therapy , Toll-Like Receptor 1/analysis , Toll-Like Receptor 2/analysis , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adalimumab , Adolescent , Adult , Aged , Antibodies, Monoclonal, Humanized , Female , Humans , Immunohistochemistry , Male , Middle Aged , Psoriasis/immunology
10.
Int J Immunopathol Pharmacol ; 23(4): 1287-8, 2010.
Article in English | MEDLINE | ID: mdl-21244781

ABSTRACT

Nonspecific lipid transfer proteins (nsLTPs) are members of the prolamine superfamily and they are found in pollen and food, as well as in latex. Due to the strong stability both against pepsin digestion and thermal denaturation, sensitisation towards these proteins is often associated with severe systemic reactions (angioedema, urticaria, asthma, anaphylaxis, etc.) following the ingestion of both raw or fresh food and cooked or preserved food. Many studies have shown reactivity towards nsLTPs both via inhalation and orally and in this study we present two cases of nsLTPs-sensitive patients who manifested the immediate onset of skin reactions following the use of cosmetic products containing these proteins. Thus, in order to prevent immediate reactions linked to their use, it is necessary to recommend nsLTPssensitive patients to avoid the topical use of products containing these proteins (and obviously the ingestion of foods containing these proteins).


Subject(s)
Carrier Proteins/immunology , Cosmetics/adverse effects , Hypersensitivity/etiology , Skin/immunology , Adult , Female , Humans , Skin Tests
11.
Clin Exp Dermatol ; 35(7): 765-70, 2010 Oct.
Article in English | MEDLINE | ID: mdl-19874355

ABSTRACT

BACKGROUND: The basophil activation test (BAT) has been recently described as a useful in vitro tool for diagnosis of allergy to Anisakis species in patients with acute urticaria. AIM: To evaluate the relationship between sensitization to Anisakis simplex and chronic urticaria (CU), using flow cytometry analysis of in vitro BAT. Methods. A. simplex sensitization was evaluated in patients with CU (n = 57) and in atopic (n = 22) and healthy controls (n = 20) by means of skin prick test (SPT), specific IgE and Anisakis-induced BAT using a triple-labelled strategy with anti-CD123, anti-human leucocyte antigen DR and anti-CD63 antibodies. During a follow-up period of 6 months in 10 patients with CU who accepted a fish-free dietary regimen, the diagnostic performance of the in vivo and in vitro methods was calculated, and changes in specific IgE and BAT were evaluated with respect to clinical response. RESULTS: A significant association between CU and A. simplex sensitization was found, with an overall prevalence of 75.4% in patients with CU (43/57) compared with 18% (4/22) and 10% (2/20) of the atopic and healthy controls, respectively (P < 0.0001). BAT (cut-off > 13%) had the highest sensitivity and specificity, with significantly better ability than specific IgE testing for the identification of A. simplex sensitization in patients with CU. During the 6-month follow-up, clinical improvement was seen in all patients, and specific IgE and BAT results decreased to normal values in 6/10 (60%) and 10/10 (100%) patients, respectively. CONCLUSIONS: BAT can be considered a reliable new in vitro method to evaluate A. simplex hypersensitivity in patients with CU, supplementing standardized procedures in both diagnosis and follow-up.


Subject(s)
Anisakis/immunology , Basophils/immunology , Dermatitis, Atopic/diagnosis , Urticaria/etiology , Adult , Animals , Antibodies, Helminth/blood , Antigens, CD/blood , Antigens, Helminth/immunology , Chronic Disease , Dermatitis, Atopic/complications , Dermatitis, Atopic/diet therapy , Female , Follow-Up Studies , Humans , Immunoglobulin E/blood , Male , Middle Aged , Platelet Membrane Glycoproteins , Seafood/parasitology , Skin Tests/methods , Tetraspanin 30 , Urticaria/diet therapy , Urticaria/immunology , Young Adult
12.
Int J Immunopathol Pharmacol ; 22(1): 227-33, 2009.
Article in English | MEDLINE | ID: mdl-19309570

ABSTRACT

There is much evidence to show the efficacy of adalimumab, a human monoclonal antibody targeting tumour necrosis factor-alpha, in the treatment of plaque psoriasis. In this open-label experience, 147 high-need patients suffering from plaque psoriasis, with a mean Psoriasis Area and Severity Index (PASI) of 18.8, and concomitant psoriatic arthritis (PsA) received subcutaneous injections of 40 mg of adalimumab every other week (EOW). This was actually the dosage regimen recommended for PsA, as the drug had not then been approved for psoriasis at the time of the patients enrolment. At week 12, an improvement of at least 50 percent of the PASI (PASI-50) was observed in 111 (77 percent) patients. Continuation of treatment in responders with adalimumab 40 mg EOW led to a sustained response, with the PASI-50 achieved by 97 percent of patients in the as-treated analysis at week 24 (PASI-75 in 82 percent and PASI-90 in 45 percent out of 109 patients who received EOW injections up to week 24). Thirty subjects who failed to attain the PASI-50 response at week 12 were treated with adalimumab 40 mg every week for a further 12 weeks. At week 24, 80 percent of these patients obtained a PASI-50 response after dose escalation. Tolerability was good in the majority of patients. Only two patients discontinued treatment because of an adverse event (repeated flu-like episodes and a pleuropericarditis of unknown origin, respectively).


Subject(s)
Antibodies, Monoclonal/therapeutic use , Psoriasis/drug therapy , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adalimumab , Adult , Aged , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Humanized , Dose-Response Relationship, Drug , Female , Humans , Male , Middle Aged
13.
J Biol Regul Homeost Agents ; 22(4): 233-7, 2008.
Article in English | MEDLINE | ID: mdl-19036225

ABSTRACT

Adalimumab is a fully human monoclonal antibody directed against tumor necrosis factor (TNF)-alpha, which is effective for the treatment of psoriasis and psoriatic arthritis (PsA). The aim of this study is to determine whether the response of psoriasis to adalimumab treatment might be influenced by certain particular factors, such as body mass index (BMI), history of biologic therapy, blood hypertension and metabolic comorbidities. For this reason, an exploratory analysis was conducted on 144 patients with psoriasis and concomitant PsA treated with adalimumab 40 mg every other week, evaluating the influence of such factors on the Psoriasis Area and Severity Index (PASI) response rate at week 12. Our preliminary results suggest that the response rate at week 12, in terms of both PASI-50 and PASI-75, appeared to be independent of the presence of hypertension and/or metabolic comorbidities. The PASI-50 response was observed more frequently in patients with BMI less than 30 as compared to obese patients (79% vs 58%, p = 0.02). Previous use of anti-TNF biologics did not appear to affect per se the rate of responders, although it was associated with a lower PASI-75 rate among responders.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Psoriasis/therapy , Adalimumab , Adult , Aged , Antibodies, Monoclonal, Humanized , Arthritis, Psoriatic/complications , Arthritis, Psoriatic/pathology , Arthritis, Psoriatic/therapy , Biological Products/therapeutic use , Body Mass Index , Female , Humans , Hypertension/complications , Male , Middle Aged , Psoriasis/complications , Psoriasis/pathology , Treatment Outcome , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Young Adult
14.
Dig Liver Dis ; 39(10): 911-6, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17719860

ABSTRACT

BACKGROUND AND AIMS: Coeliac disease is an autoimmune disorder characterised by high levels of anti-endomysial and anti-tissue transglutaminase autoantibodies in sera and media of cultured intestinal mucosa biopsies from affected patients. In this study, we wished to investigate whether anti-endomysial and anti-tissue transglutaminase antibodies can also be detected in culture media of oral mucosa specimens, and whether the mouth can be used as an area of immunological testing for coeliac disease. METHODS: Small intestine and cheek biopsy samples taken from 16 patients with active coeliac disease and from 11 controls were cultured in vitro for 48 h at 37 degrees C in presence of medium alone. Anti-endomysial and anti-tissue transglutaminase were detected in sera and in supernatants of these cultured biopsy samples by indirect immunofluorescence and enzyme immunoassay (EIA), respectively. RESULTS: Anti-endomysial and anti-tissue transglutaminase were positive in sera of 15/16 coeliac disease patients. Culture media of intestinal mucosa samples from 14/16 coeliac disease patients were anti-endomysial positive, while the same antibodies were positive in supernatants of cultured oral mucosa samples from 15/16 coeliac disease patients. Anti-tissue transglutaminase were positive in both intestinal and oral culture media of 15/16 coeliac disease patients. Neither anti-endomysial nor anti-tissue transglutaminase were found in sera or in culture supernatants of both intestinal and oral biopsy samples from 11 controls. CONCLUSIONS: Our study suggests a new immunological site to detect the pathognomonic autoantibodies of coeliac disease and confirms that the mouth is involved in this illness.


Subject(s)
Autoantibodies/analysis , Celiac Disease/immunology , Immunoglobulin A/immunology , Mouth Mucosa/pathology , Transglutaminases/immunology , Adult , Aged , Biopsy , Celiac Disease/enzymology , Celiac Disease/pathology , Cells, Cultured , Female , Fluorescent Antibody Technique, Indirect , Humans , Immunoenzyme Techniques , Intestinal Mucosa/enzymology , Intestinal Mucosa/pathology , Male , Middle Aged
15.
Clin Exp Rheumatol ; 25(3): 373-7, 2007.
Article in English | MEDLINE | ID: mdl-17631732

ABSTRACT

OBJECTIVE: To test the reliability of a new enzyme-linked immunosorbent assay (ELISA) to identify anti-RNA polymerase III (RNAP III) positive sera from Italian patients with Systemic Sclerosis (SSc) and other chronic inflammatory disorders. METHODS: A comparison between the new ELISA for anti-RNAP III and the gold standard technique, immunoprecipitation (IP), was first performed on 106 SSc patients, 16 patients with other connective tissue diseases and 10 healthy subjects. A further ELISA evaluation was performed on 224 SSc patients, 120 subjects with other rheumatic or infectious diseases, and 81 healthy controls. RESULTS: Plotting ELISA and IP data in a Receiver Operator Characteristic curve, the ELISA cut-off value providing the best specificity (99.1%) and sensibility (100%) was 28 U/ml (AUC=0.999; p<0.0001). Using this cut-off in the second analysis, anti-RNAP III positive results were found in 41 (18.3%) SSc patients, all negative for anticentromere or anti-topoisomerase I antibodies, while only 3 subjects tested positive among the 120 sera collected from other patients. All the healthy subjects were negative. CONCLUSION: This new ELISA for anti-RNAP III is highly accurate when a proper cut-off value is employed and represents a valid substitute to IP in a clinical setting.


Subject(s)
Antibodies/blood , Enzyme-Linked Immunosorbent Assay/methods , RNA Polymerase III/immunology , Scleroderma, Systemic/immunology , Adult , Aged , Aged, 80 and over , Humans , Immunoprecipitation/methods , Italy , Middle Aged , ROC Curve , Reference Values , Reproducibility of Results , Scleroderma, Systemic/blood , Scleroderma, Systemic/ethnology , Sensitivity and Specificity
17.
Allergy ; 61(9): 1071-7, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16918509

ABSTRACT

BACKGROUND: Functional autoantibodies against the alpha-chain of the high-affinity IgE receptor (FcepsilonRIalpha) identify a subset of patients with chronic urticaria (CU) due to autoreactivity, as assessed by an in vivo positive response to autologous serum skin test (ASST). We performed a study to standardize the serum-induced basophil activation assay by flow cytometry (FCM) using a new tricolour method, assessing the diagnostic performance of this test in discriminating between ASST+ and ASST- CU patients. METHODS: Sera of 64 CU patients (22 ASST+ CU and 42 ASST- CU) and 10 healthy subjects were tested for their ability to induce basophil CD63 expression when incubated with whole blood of both atopic (DA) and non-atopic donors (DNA). Using a triple-labelled strategy with anti-CD123, anti-HLA-DR and anti-CD63 antibodies, CD63+ basophils were identified on a selected population of CD123+ HLA-DR- cells. In 3 ASST+ CU patients who underwent cyclosporine therapy, the assay was performed before and after treatment. RESULTS: The ASST+ CU sera resulted in a significant higher induction of basophil CD63 expression compared with ASST- CU and healthy donors sera; when whole blood from DA was used, sensitivity and specificity of the assay were 95.5% and 90.5% respectively. ASST+ CU serum activity was significantly decreased during cyclosporine A treatment, in parallel with clinical remission. CONCLUSIONS: Chronic urticaria serum-induced CD63 expression assay performed on DA whole blood by means of our tricolour FCM method could be the most useful tool for identification of a subset of patients with autoimmune CU and may become a promising tool also for monitoring treatment efficacy.


Subject(s)
Antigens, CD/genetics , Basophils/metabolism , Flow Cytometry , Platelet Membrane Glycoproteins/genetics , Serum/immunology , Urticaria/diagnosis , Urticaria/immunology , Adult , Antigens, CD/biosynthesis , Antigens, CD/blood , Basophils/immunology , Cell Separation , Chronic Disease , Female , Flow Cytometry/methods , Humans , Hypersensitivity, Immediate/blood , Hypersensitivity, Immediate/immunology , Male , Middle Aged , Platelet Membrane Glycoproteins/biosynthesis , Sensitivity and Specificity , Tetraspanin 30 , Urticaria/blood
18.
Clin Exp Immunol ; 139(3): 551-7, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15730402

ABSTRACT

We studied the expression of adhesion molecules affecting recirculation and homing on peripheral blood CD4(+) T cells of patients with systemic sclerosis (SSc), in order to evaluate whether the distribution of tissue targeted subsets could reflect the participation of internal organs or the extent of cutaneous involvement [i.e. limited cutaneous (lc) and diffuse cutaneous (dc)]. Peripheral blood mononuclear cells (PBMC) from 51 patients with SSc and 19 sex- and age-matched controls were investigated by cytofluorimetric analysis for lymphocyte subpopulations carrying the following surface molecules: CD3, CD4, CLA, alpha4beta7 and alpha4beta1. Standard routine biochemistry and clinical examinations were also performed in all patients. We found that both alpha4beta1(+) and alpha4beta7(+) cells within the CD4(+) T cell population were significantly increased, while CLA(+) CD4(+) T cells were significantly reduced in SSc, compared to healthy donors. Significantly lower absolute numbers of alpha4beta7(+) cells were found in lc- compared to dc-SSc. Patients with oesophageal involvement had high numbers of alpha4beta7(+) cells, while those with nephritis also showed low levels of CLA(+) cells. Lung involvement was related directly to alpha4beta1(+) cell numbers and inversely to alpha4beta7(+) CD4 cell numbers. Taken together, our findings demonstrate that distinct CD4(+) T cell populations with selective homing properties show changes from normal distribution in SSc, and such changes are related to clinical expression and organ involvement in the course of the disease.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , Receptors, Lymphocyte Homing/metabolism , Scleroderma, Systemic/immunology , Skin/immunology , Adult , Antigens, Differentiation, T-Lymphocyte , Antigens, Neoplasm , Case-Control Studies , Chi-Square Distribution , Female , Flow Cytometry , Humans , Integrin alpha4beta1/analysis , Integrins/analysis , Lymphocyte Count , Male , Membrane Glycoproteins/analysis , Middle Aged , Scleroderma, Diffuse/immunology , Scleroderma, Limited/immunology
19.
Clin Exp Immunol ; 138(3): 540-6, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15544634

ABSTRACT

Systemic sclerosis (SSc) is a connective tissue disorder characterized by excessive collagen deposition in the skin and internal organs. Several cytokines and chemokines have been implicated in the induction of fibrosis, but a definitive relationship between specific cytokines and organ involvement has not been established yet. Serum samples, PBMC and T cell lines (TCL) obtained from 54 patients affected by SSc and 20 healthy donors (HD) were examined by ELISA for Interferon-gamma (IFN-gamma ), interleukin (IL)-4, IL-6, IL-10, IL-18, Transforming growth factor (TGF)-beta1, Tumour necrosis factor (TNF)-alpha, sCD30, Macrophage derived chemokine (MDC), Monocyte chemoattractant protein (MCP)-1, Macrophage inflammatory protein (MIP)-1alpha and Regulated on activation normal T-cell expressed and secreted (RANTES). In all the SSc serum samples, we found significantly increased levels of IL6, TNFalpha and MCP-1 but reduced amounts of gamma-IFN and MDC. IL6, IL10, IL18, MIP-1alpha and TNFalpha measured in supernatants from PHA-stimulated PBMC and IL6, MCP-1 and RANTES in supernatants from stimulated TCL were also increased in patients. MDC was decreased in all the biological SSc sources studied. TGF-beta1, IL10, and sCD30 were produced at a significantly lower level by SSc TCL. Serum IL6 and sCD30 levels were significantly increased in dc-SSc patients compared to lc-SSc as were levels of MCP-1 produced by PBMC and IL10 from TCL. We observed a strict relationship between pulmonary fibrosis and IL10, MCP-1 (both from TCL) and serum IL6. Kidney involvement was related to serum MCP-1 levels and IL18 production from PBMC. Oesophageal involvement correlated with MDC production from PBMC and IL10 synthesis by TCL. We showed that IL-6, IL-10, MDC and MCP-1 are variably associated with internal organ involvement and allow the discrimination between limited and diffuse forms of the disease.


Subject(s)
Chemokines/analysis , Cytokines/analysis , Scleroderma, Systemic/immunology , Cell Line , Esophageal Motility Disorders/complications , Esophageal Motility Disorders/immunology , Female , Humans , Hypertension, Pulmonary/complications , Hypertension, Pulmonary/immunology , Interleukin-10/analysis , Interleukin-6/analysis , Kidney Diseases/complications , Kidney Diseases/immunology , Leukocytes, Mononuclear/immunology , Male , Middle Aged , Pulmonary Fibrosis/complications , Pulmonary Fibrosis/immunology , Tumor Necrosis Factor-alpha/analysis
20.
Clin Exp Immunol ; 137(3): 595-600, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15320912

ABSTRACT

Cutaneous infiltration of activated CD4(+) T cells and eosinophils is an early event in blister formation during bullous pemphigoid (BP), suggesting that the trafficking of circulating leucocytes through the sites of inflammation, their activation and cytokine release is crucial in the pathogenesis of the disease. IL-16 is a major chemotactic factor able to recruit CD4(+) cells in the skin during inflammation and to induce the expression of functional high-affinity interleukin (IL)-2 receptors, thus contributing to cellular activation and proliferation. We performed a study in order to evaluate the presence of IL-16 in skin samples and sera and blister fluids of patients affected with BP in active phase of the disease (n = 39), compared with healthy donors studied as control group. Ten patients were also evaluated before and after steroid therapy. Our results demonstrated that IL-16 was expressed strongly by keratinocytes and by dermal infiltrating CD4(+) T lymphocytes in lesional skin of BP patients. High levels of IL-16 were detected in sera and blisters of BP, significantly higher in respect to healthy donors. When patients were investigated for the presence of eosinophil cationic protein (ECP) and soluble CD30 (sCD30) to reveal signs of eosinophils and Th2-cells activation, we found a positive correlation between IL-16 serum levels and both ECP and sCD30, suggesting that IL-16 is involved in Th2 lymphocytes and eosinophils recruitment during BP.


Subject(s)
Interleukin-16/analysis , Pemphigoid, Bullous/immunology , Skin/immunology , Acute Disease , Aged , Blood Proteins/analysis , CD4-Positive T-Lymphocytes/immunology , Case-Control Studies , Eosinophil Granule Proteins , Eosinophils/immunology , Female , Humans , Leukocyte Count , Lymphocyte Activation , Male , Middle Aged , Ribonucleases/analysis , Th2 Cells/immunology
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