Immunology and Allergology Laboratory Unit

Firenze, Italy

Immunology and Allergology Laboratory Unit

Firenze, Italy
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Yee A.,INOVA Diagnostics Inc. | Webb T.,INOVA Diagnostics Inc. | Seaman A.,INOVA Diagnostics Inc. | Infantino M.,Immunology and Allergology Laboratory Unit | And 8 more authors.
Immunologic Research | Year: 2014

Anti-citrullinated protein antibodies (ACPA) are important serological markers in the diagnosis of rheumatoid arthritis (RA) and are part of the recent disease classification criteria. However, there is a strong need for reliable markers for measuring and predicting joint damage and disease activity. Recently, antibodies directed against carbamylated antigens (anti-CarP antibodies) were identified. A total of 120 RA patients were tested for anti-CCP antibodies using different methods and for anti-CarP antibodies using carbamylated fetal calf serum according to the method described by Shi et al. Additionally, ACPA fine specificities (to three citrullinated peptides) were measured. Disease activity was assessed at baseline using the disease activity score 28 (DAS28) in 80 patients. For 40 RA patients, joint erosion score (JES) was established. The median JES was 14.1 with a standard deviation of 11.5. Anti-CarP antibodies were correlated with joint erosion score (ρ = 0.34, 95 % CI 0.03–0.59; p = 0.0332). No correlation between ACPA and joint erosion score was observed. No individual marker correlated with DAS28. When one ACPA peptide was combined with anti-CarP antibodies in a score (ACPA peptide 1 divided by anti-CarP), a statistically relevant correlation was found (p = 0.0264). In this small cohort, the presence of anti-CarP antibodies, but not ACPA correlate with joint erosion score. Anti-CarP antibodies combined with ACPA fine specificities correlated with DAS28. Therefore, anti-CarP antibodies might represent a promising marker to predict joint damage and disease activity in RA patients. © 2014, Springer Science+Business Media New York.


Benucci M.,Rheumatology Unit | Saviola G.,Rheumatology and Rehabilitation Unit | Baiardi P.,University of Pavia | Manfredi M.,Immunology and Allergology Laboratory Unit
Rheumatology International | Year: 2011

The cost-effectiveness of treatments that have the potential to change the "natural history" of a chronic progressive disease has to be evaluated over the long term. Cost-effectiveness estimates have been based on the concept that, with treatment, patients will not progress to the next level(s) of disease severity or will take a longer time to progress, thus avoiding or delaying the high costs and low utility associated with more severe disease. This analysis focused on the use of Rituximab in treating patients with moderate to severe RA for whom at least one anti-TNFα blocking agent had failed. The aim of our study was to evaluate the cost-effectiveness in 32 patients with rheumatoid arthritis in therapy with a single infusion of Rituximab 1,000 mg given on days 1 and 15 of each month for 1 year. After 6 months of treatment, we observed for all 32 patients a total quality-adjusted life year (QALY) gained of 11,840 with an average of 0.37 QALY for a single patient, a treatment cost of €5,610 and a QALY/cost ICER (incremental cost-effectiveness ratio) of €15,114. After 1 year of treatment, we observed data for 28 patients with a total QALY gained of 11,480 with an average of 0.41 QALY for a single patient, a treatment cost of €9,690 and a QALY/cost ICER (incremental cost-effectiveness ratio) of €23,696. The benefit of using Rituximab is cost-effectiveness with a QALY/gained under the acceptable threshold of €50,000 in our observational study. These are important data for discussion from the economic point of view when we choose a biologic therapy for rheumatoid arthritis in clinical practice. © 2010 Springer-Verlag.


Benucci M.,Rheumatology Unit | Gobbi F.L.,Rheumatology Unit | Meacci F.,Immunology and Allergology Laboratory Unit | Manfredi M.,Immunology and Allergology Laboratory Unit | And 6 more authors.
Biologics: Targets and Therapy | Year: 2015

Although anti-TNF drugs have changed the clinical course of rheumatoid arthritis (RA), survival rates and resistance-to-therapy data confirm that about 30% of RA patients fail to respond. The aim of this study was to evaluate the correlations between the development of antidrug antibodies, specific IgG4 antibodies against TNF inhibitors, and resistance to therapy in RA patients. This retrospective study involved 1 29 patients with established RA naïve to biological agents (98 females and 32 males, mean age 56.7±12.3 years, disease duration 6.3±1.2 years, baseline Disease Activity Score [DAS]-28 3.2–5.6) who received treatment with anti-TNF agents after the failure of conventional disease-modifying antirheumatic drugs (32 received infliximab [IFX], 58 etanercept [ETN], and 39 adalimumab [ADA]). After 6 months of treatment, the patients were classifed as being in remission (DAS28 <2.6), having low disease activity (LDA; DAS28 2.6–3.2), or not responding (NR: DAS28 >3.2). The patients were also tested for serum antidrug antibodies and IgG4 antibodies against TNF inhibitors. After 24 weeks of treatment, 38% of the ETN-treated patients and 28% of those treated with ADA had injection-site reactions; the rate of systemic reactions in the IFX group was 25%. The differences among the three groups were not statistically significant (P=0.382; ETN versus ADA P=0.319). The percentages of patients with adverse events stratified by drug response were: LDA 8% and NR 18% in the ADA group; in remission 3%, LDA 22%, and NR 10% in the ETN group; and LDA 6% and NR 1 6% in the IFX group (P=0.051). The percentages of patients with antidrug antibodies were: ADA 33.3%, ETN 11.5%, and IFX 10.3% (P=0.025; ADA versus ETN P=0.015). The percentages of patients with IgG4 antibodies were: ADA 6%, ETN 13%, and IFX 26% (P=0.017; ADA versus ETN P=0.437). Associations between antidrug antibodies, specific IgG4 antibodies, and adverse reactions were not significant for any of the three drugs. IgG4 levels were higher in the ADA group than in the other two groups, and higher in the patients with worse DAS28 (NR) and in those experiencing adverse events. These data suggest a possible association between IgG4levels and worse DAS28 (r2=5.8%, P=0.011). The presence of specific IgG4 antibodies against TNF blockers in patients with RA might affect the drugs’ activity. Patients with injection-site reactions and IgG4 against ETN may show a decreased response. © 2015 Benucci et al.


Benucci M.,Rheumatology Unit | Saviola G.,Rheumatology and Rehabilitation Unit | Meacci F.,Immunology and Allergology Laboratory Unit | Manfredi M.,Immunology and Allergology Laboratory Unit | And 6 more authors.
Open Rheumatology Journal | Year: 2013

The use of tumour necrosis factor (TNF) antagonists (infliximab [IFN], etanercept [ETN], adalimumab [ADA]) has changed the course of many rheumatic diseases, including rheumatoid arthritis (RA). However, some questions concerning their safety have emerged since their approval because they can trigger immunisation, induce rare type I and III hypersensitivity, and cause acute and delayed reactions. The aim of this study was to evaluate the correlations between hypersensitivity reactions to biological agents, disease activity and the development of class-specific IgA and IgM antibodies against the three anti-TNF agents in patients with RA. This longitudinal observational study involved consecutive outpatients with active RA who started treatment with IFN (n=30), ETN (n=41) or ADA (n=28). Clinical data and systemic and local side effects were collected prospectively at baseline and after six months of anti-TNF treatment. Serum samples were taken at the same time points in order to measure antibodies against the TNF blockers, anti-nuclear (ANA) and anti-dsDNA antibodies. The IgA and IgM antibodies specific to all three anti-TNF-α agents were analysed using ImmunoCaP Phadia- Thermofisher especially developed in collaboration with the laboratory of Immunology and Allergy, San Giovanni di Dio, Florence. The mean age of the 99 patients (86% females) was 54.6±12.4 years, and the median disease duration was 11.2±.3.2 years (range 3-14.3). The three treatment groups were comparable in terms of age, gender, rheumatoid factor and anticitrullinated peptide (CCP) antibody positivity, and baseline C-reactive protein levels, erythrocyte sedimentation rate, 28- joint disease activity scores, and concomitant medications. Twelve patients treated with INF (40%) had anti-IFN IgM, and two (6%) anti-IFN IgA; 19 patients treated with ADA (68%) had anti-ADA IgM, and four (6%) anti-ADA IgA; and 27 patients treated with ETN (66%) had anti-ETN IgM, and 24 (58%) anti-ETN IgA. There were five systemic reactions in the IFN group, and seven adverse local reactions in both the ADA and the ETN group. There was no correlation between drug-specific IgA and IgM antibodies (p=0.65). There was also no correlation between the antibodies and disease activity after six months of treatment (r=0.189;p=0.32). Our findings show that the development of antibodies against IFN, ADA or ETN of IgA and IgM class are not related to any decrease in efficacy or early discontinuation of anti-TNF treatment in RA patients, nor to systemic and local reactions. Further studies of larger series of RA patients are needed to confirm the relationships between the development of drug-specific antibodies, serum TNF blocker levels, and disease activity. © Benucci et al.; Licensee Bentham Open.


Seaman A.,INOVA Diagnostics Inc. | Darrah E.,Johns Hopkins University | Infantino M.,Immunology and Allergology Laboratory Unit | Meacci F.,Rheumatology Unit | And 3 more authors.
Autoimmunity Reviews | Year: 2016

Background: Recently, antibodies directed against peptidyl arginine deiminase 3 and 4 (anti-PAD3/PAD4 antibodies), calcium-dependent enzymes that catalyze the conversion from arginine to citrulline, have been described. Furthermore, antibodies that cross-react between PAD3 and PAD4 cause increased PAD4 activity and consequently correlate with joint damage. This study analyzes the correlation of anti-PAD3 antibodies with joint damage. Methods: To validate the novel chemiluminescent immunoassay (CIA) for the detection of anti-PAD3 antibodies, 20 samples were tested by CIA and by immunoprecipitation (IP). Next, 39 RA patients with available joint erosion score (JES), Total Sharp Score (TSS) and Joint Space Narrowing Score (JSNS) were tested for anti-CCP (using different methods) and anti-PAD3 antibodies by CIA. Results: Excellent correlation was observed between the CIA and IP for the detection of anti-PAD3 antibodies (rho = 0.85, p < 0.0001). The median JES of our 39 patients was 14.1 with a standard deviation of 11.5. Anti-PAD3 antibody levels (rho = 0.39, 95% CI = 0.1-0.6; p = 0.0149) were correlated with JES. No correlation was found with TSS and JSNS. In this cohort, ACPA measured using different anti-CCP assays did not correlate with the JES. Conclusion: In our cohort, anti-PAD3 antibodies correlate with joint erosion score. Therefore, anti-PAD3 antibodies might represent promising markers to predict joint damage in RA patients. © 2016 Elsevier B.V.


PubMed | IRCCS Galeazzi Orthopedic Institute, Allergy and Clinical Immunology Unit, Rheumatology Unit, University of Regensburg and 2 more.
Type: | Journal: Biologics : targets & therapy | Year: 2015

Although anti-TNF drugs have changed the clinical course of rheumatoid arthritis (RA), survival rates and resistance-to-therapy data confirm that about 30% of RA patients fail to respond. The aim of this study was to evaluate the correlations between the development of antidrug antibodies, specific IgG4 antibodies against TNF inhibitors, and resistance to therapy in RA patients. This retrospective study involved 129 patients with established RA nave to biological agents (98 females and 32 males, mean age 56.712.3 years, disease duration 6.31.2 years, baseline Disease Activity Score [DAS]-28 3.2-5.6) who received treatment with anti-TNF agents after the failure of conventional disease-modifying antirheumatic drugs (32 received infliximab [IFX], 58 etanercept [ETN], and 39 adalimumab [ADA]). After 6 months of treatment, the patients were classified as being in remission (DAS28 <2.6), having low disease activity (LDA; DAS28 2.6-3.2), or not responding (NR: DAS28 >3.2). The patients were also tested for serum antidrug antibodies and IgG4 antibodies against TNF inhibitors. After 24 weeks of treatment, 38% of the ETN-treated patients and 28% of those treated with ADA had injection-site reactions; the rate of systemic reactions in the IFX group was 25%. The differences among the three groups were not statistically significant (P=0.382; ETN versus ADA P=0.319). The percentages of patients with adverse events stratified by drug response were: LDA 8% and NR 18% in the ADA group; in remission 3%, LDA 22%, and NR 10% in the ETN group; and LDA 6% and NR 16% in the IFX group (P=0.051). The percentages of patients with antidrug antibodies were: ADA 33.3%, ETN 11.5%, and IFX 10.3% (P=0.025; ADA versus ETN P=0.015). The percentages of patients with IgG4 antibodies were: ADA 6%, ETN 13%, and IFX 26% (P=0.017; ADA versus ETN P=0.437). Associations between antidrug antibodies, specific IgG4 antibodies, and adverse reactions were not significant for any of the three drugs. IgG4 levels were higher in the ADA group than in the other two groups, and higher in the patients with worse DAS28 (NR) and in those experiencing adverse events. These data suggest a possible association between IgG4 levels and worse DAS28 (r (2)=5.8%, P=0.011). The presence of specific IgG4 antibodies against TNF blockers in patients with RA might affect the drugs activity. Patients with injection-site reactions and IgG4 against ETN may show a decreased response.


PubMed | INOVA Diagnostics Inc., Johns Hopkins University, Immunology and Allergology Laboratory Unit and Rheumatology Unit
Type: Journal Article | Journal: Autoimmunity reviews | Year: 2016

Recently, antibodies directed against peptidyl arginine deiminase 3 and 4 (anti-PAD3/PAD4 antibodies), calcium-dependent enzymes that catalyze the conversion from arginine to citrulline, have been described. Furthermore, antibodies that cross-react between PAD3 and PAD4 cause increased PAD4 activity and consequently correlate with joint damage. This study analyzes the correlation of anti-PAD3 antibodies with joint damage.To validate the novel chemiluminescent immunoassay (CIA) for the detection of anti-PAD3 antibodies, 20 samples were tested by CIA and by immunoprecipitation (IP). Next, 39 RA patients with available joint erosion score (JES), Total Sharp Score (TSS) and Joint Space Narrowing Score (JSNS) were tested for anti-CCP (using different methods) and anti-PAD3 antibodies by CIA.Excellent correlation was observed between the CIA and IP for the detection of anti-PAD3 antibodies (rho=0.85, p<0.0001). The median JES of our 39 patients was 14.1 with a standard deviation of 11.5. Anti-PAD3 antibody levels (rho=0.39, 95% CI=0.1-0.6; p=0.0149) were correlated with JES. No correlation was found with TSS and JSNS. In this cohort, ACPA measured using different anti-CCP assays did not correlate with the JES.In our cohort, anti-PAD3 antibodies correlate with joint erosion score. Therefore, anti-PAD3 antibodies might represent promising markers to predict joint damage in RA patients.

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