RESUMO
OBJECTIVE: To evaluate the diagnostic accuracy of anticarbamylated protein antibodies (CarP), alone and in combination with traditional biomarkers (rheumatoid factor [RF] and anticitrullinated peptide antibodies [ACPA]), in established rheumatoid arthritis (RA). METHODS: A commercially available enzyme-linked immunosorbent assay (ELISA) kit was used to assess CarP concentrations in serum samples of 200 established RA and 206 controls (115 healthy donors and 55 patients with other rheumatic diseases). Main outcome measures were sensitivity, specificity, and area under the curve (AUC; 95% confidence interval [CI]). Difference in accuracy was evaluated by comparison of the respective AUCs. RESULTS: A serum CarP cut-off of 1.47 ng/ml or more differentiated patients with RA from controls with 30% sensitivity, 97.1% specificity, and good accuracy (AUC[95%CI] = 0.83[0.79-0.86], P < 0.0001). However, it showed moderate diagnostic accuracy in seronegative RA patients: sensitivity 17.9%, specificity 96.9%, and AUC (95% CI) = 0.69 (0.63-0.75). The diagnostic accuracy of CarP_ACPA and CarP_RF combinations was significantly superior to that of ACPA and RF alone (P < 0.0001 and P = 0.015, respectively), but not to that of ACPA_RF combination (P = 0.089) In addition, the CarP_ACPA_RF combination did not improve the diagnostic accuracy of the ACPA_RF combination (AUC mean difference [95% CI] = 0.006 [-0.001 to 0.015], P = 0.10). The number of positive autoantibodies (0, 1, 2, or 3) was not significantly associated with moderate-severe disease (Disease Activity Score-28 [DAS-28] > 3.2) in adjusted multiple regression analysis. CONCLUSION: CarP has good diagnostic accuracy in established RA but not in seronegative RA. The addition of CarP to ACPA and RF alone or in combination does not significantly enhance the diagnostic accuracy of ACPA_RF combination.
RESUMO
OBJECTIVE: While CD4+ T-cells are traditionally regarded as the main pathogenic T-cell subpopulation in psoriatic arthritis (PsA), the role of circulating CD8+ T-cells remains poorly characterized. We evaluated the differential representation of CD8+ T-cell subpopulations in peripheral blood (PB) of PsA patients. PATIENTS AND METHODS: CD8+IL-17+, CD8+IFNγ+ and CD8+IL-17-IL-22+ T-cells were evaluated by flow-cytometry in 25 consecutive PsA patients, 7 rheumatoid arthritis (RA) patients, 16 patients with psoriasis, and 26 healthy controls (HC). RESULTS: We observed a significant expansion of circulating IFN-γ producing CD8+ T-cells in PsA when compared to psoriasis [21.2 (6.9-55.8)% vs. 3.8 (0.7-11.8)%, p < 0.0001] and HC samples [21.2 (6.9-55.8)% vs. 4.05 (0.44-19.8)%, p < 0.0001]. A frequency of circulating IFN-γ producing CD8+T-cells ≥ 9% distinguished PsA from psoriasis patients with a specificity of 84% and a sensitivity of 87.5% [AUC = 0.9 (0.80-0.99), p < 0.0001]. In addition, we found a significant expansion of circulating IL-17 producing CD8+ T cells in RA patients when compared to PsA, psoriasis and HC samples. By contrast, there were no significant between-group differences in the prevalence of circulating IL-22 producing CD8+ T-cells. In PsA patients there was a significant correlation between number of swollen joints and frequency of circulating IFN-γ producing CD8+ T-cells, and between extent and severity of psoriasis and frequency of circulating IL-17 producing CD8+ T-cells. CONCLUSIONS: Circulating IFNγ-producing CD8+ T-cells are raised in PsA when compared to psoriasis, suggesting a potential pathogenetic involvement of CD8+ T-cells and IFNγ production in chronic joint inflammation and damage. The significant enrichment of circulating IL-17 producing CD8+ T-cells in RA when compared to PsA warrants functional characterization and confirmation in larger studies. We found no significant enrichment of circulating IL-22 producing CD8+ T-cells in PsA, RA and psoriasis.
Assuntos
Artrite Psoriásica/patologia , Linfócitos T CD8-Positivos/metabolismo , Adulto , Idoso , Artrite Psoriásica/imunologia , Artrite Reumatoide/imunologia , Artrite Reumatoide/patologia , Linfócitos T CD8-Positivos/citologia , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Interferon gama/sangue , Interleucina-17/sangue , Interleucinas/sangue , Masculino , Pessoa de Meia-Idade , Psoríase/imunologia , Psoríase/patologia , Interleucina 22RESUMO
Endogenous retroviruses (HERV) are believed to be pathogenic in several autoimmune diseases. Among them, HERV-K viruses have been reported recently to be involved in the pathogenesis of rheumatoid arthritis (RA). In this study we have explored the role of humoral immune response against HERV-K as a potential pathogenetic mechanism in RA. Four different peptides from the extracellular portion of the env protein of HERV-K (env-su19-37 , env-su109-126 , env-su164-186 , env-su209-226 ) were selected by bioinformatic analysis on the basis of their putative immunogenicity. Indirect enzyme-linked immunosorbent assay (ELISA) was then carried out to quantify antibodies against those peptides on blood samples of 70 consecutive RA patients and 71 healthy controls (HC). Differences between the two groups were analysed using the Mann-Whitney test. Potential correlations between RA laboratory, clinical descriptors and immunoglobulin (Ig)G levels were explored by bivariate regression analysis. Serum autoantibodies against one of four tested peptides of HERV-K (env-su19-37 ) were significantly higher in RA than in HC (19 versus 3%, P = 0·0025). Subgroup analysis showed no association between anti-HERV-K peptide humoral response and clinical, serological and clinimetric RA disease descriptors. Serum from RA patients in our series reacted significantly against HERV-K env-su19-37 peptide in comparison to the general population suggesting a role for the HERV-K- related, secondary antigenic-driven immune response in the pathogenesis of RA. Further studies are needed to confirm these results and to explore the role of this HERV-K surface peptide as a potential therapeutic target.
Assuntos
Artrite Reumatoide/imunologia , Retrovirus Endógenos/imunologia , Proteínas do Envelope Viral/imunologia , Adulto , Idoso , Anticorpos Antivirais/sangue , Artrite Reumatoide/sangue , Autoanticorpos/sangue , Estudos de Casos e Controles , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunidade Humoral , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Peptídeos/imunologiaRESUMO
Little is known regarding the environmental factors at play in igniting rheumatoid arthritis (RA) autoimmunity, although an association between Mycobacteria and RA has been documented. This pilot study focused on examining a possible involvement of Mycobacterium tuberculosis (MTB) and Mycobacterium avium ss. paratuberculosis (MAP) in RA. We measured out the serum levels of IgG antibody against different mycobacterial antigens in Sardinian patients and controls, by an enzyme-linked immunosorbent assay. The population study was composed of 61 RA patients under different therapies and 52 healthy controls, whereas the antigens tested were MTB lipoarabinomannan (ManLAM), MAP heath shock protein 70, and MAP protein tyrosine phosphatase. The frequencies of anti-ManLAM antibodies were higher in the RA group (23 %) compared to the healthy controls (5.7 %) (AUC = 0.7; p < 0.0001), whereas serum reactivity to MAP antigens was not observed. ManLAM antigen was also detected in the plasma of three RA patients (which were anti-ManLAM antibody positive) by Western blot analysis using anti-Man-LAM monoclonal antibodies. The data produced corroborate the hypothesis of a potential association between MTB ManLAM and RA disease, but so far, further studies are necessary to understand its role in RA pathogenesis.
Assuntos
Anticorpos Antibacterianos/imunologia , Artrite Reumatoide/etnologia , Artrite Reumatoide/imunologia , Lipopolissacarídeos/imunologia , Mycobacterium tuberculosis , Idoso , Anticorpos Monoclonais/imunologia , Antígenos de Bactérias/química , Artrite Reumatoide/complicações , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Proteínas de Choque Térmico HSP70/química , Humanos , Imunoglobulina G/sangue , Itália , Tuberculose Latente/complicações , Tuberculose Latente/microbiologia , Lipopolissacarídeos/química , Masculino , Pessoa de Meia-Idade , Mycobacterium avium subsp. paratuberculosis , Projetos Piloto , Proteínas Tirosina Fosfatases/químicaAssuntos
Artrite Reumatoide/complicações , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/epidemiologia , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/epidemiologia , Adalimumab , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Feminino , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico , Prevalência , Fatores de RiscoRESUMO
Many lines of independent research have pointed out the role of oxidative stress as a fascinating pathogenic link between the three main hallmarks of systemic sclerosis (SSc), viz. humoral and cellular immunity activation, microvascular damage and widespread tissue fibrosis. Therefore counteracting oxidative stress may have a favourable impact on clinical features and progression of disease. It is becoming clearer that Iloprost, a synthetic stable analogue of prostacycline, currently employed in the treatment of SSc vascular features, also possess anti-oxidative properties beside its prostaglandin-like vasodilatory and antiaggregant effects. This brief review is aimed to discuss available clinical evidences supporting Iloprost antioxidant action and focus on putative molecular pathways underlying it.
Assuntos
Antioxidantes/uso terapêutico , Iloprosta/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Escleroderma Sistêmico/tratamento farmacológico , Vasodilatadores/uso terapêutico , Antioxidantes/farmacologia , Medicina Baseada em Evidências , Humanos , Iloprosta/farmacologia , Inibidores da Agregação Plaquetária/uso terapêutico , Escleroderma Sistêmico/metabolismo , Superóxido Dismutase/efeitos dos fármacos , Resultado do Tratamento , Vasodilatadores/farmacologiaRESUMO
Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by a hypercoagulable state related to persistently elevated levels of antiphospholipid antibodies (aPL). Current treatment for APS is only partially effective and new therapies are strongly needed. We report on a case of a 50 years old man with APS who suffered from recurrent thromboembolic episodes despite conventional anticoagulant treatment. Eight years after the first thrombotic manifestation he was diagnosed with a large B cell non-Hodgkin lymphoma. Treatment with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) plus rituximab was started with partial clinical remission of lymphoma and normalization of aPL levels with a three years follow-up period free of thrombotic episodes.A review of the literature revealed that only 12 case reports on the use of rituximab in patients with primary, secondary and catastrophic APS have been published. Current knowledge clearly suggests the need for clinical trials to evaluate the effect of rituximab in the treatment of resistant APS.
Assuntos
Anticorpos Antifosfolipídeos/sangue , Anticorpos Monoclonais/uso terapêutico , Anticoagulantes/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Síndrome Antifosfolipídica/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Linfoma Difuso de Grandes Células B/complicações , Tromboembolia/tratamento farmacológico , Anticorpos Monoclonais Murinos , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/imunologia , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Evolução Fatal , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Rituximab , Tromboembolia/imunologia , Resultado do Tratamento , Vincristina/administração & dosagemRESUMO
BACKGROUND: Oxidative stress has been considered a leading factor in the pathogenesis of systemic sclerosis (SSc). Consistently with this hypothesis the determination of urinary isoprostanes, a reliable method for evaluation of oxidative stress, has recently showed increased levels of isoprostanes in SSc patients. Data about the effect on oxidative stress of accepted therapies for SSc such as iloprost therapy are lacking. OBJECTIVE: The aim of this prospective study was to verify whether iloprost therapy in patients with SSc acutely reduces oxidative stress assessed by determination of 8-Iso PGF
Assuntos
Iloprosta/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Escleroderma Sistêmico/tratamento farmacológico , Escleroderma Sistêmico/metabolismo , Vasodilatadores/administração & dosagem , Adulto , Idoso , Dinoprosta/análogos & derivados , Dinoprosta/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
There is strong evidence that the determination of autoantibodies against filaggrine is a very useful tool for the diagnosis of rheumatoid arthritis (RA). Anti-cyclic citrullinated peptide antibodies (Anti-CCP)-ELISA appear to be the most efficient test among those available for the detection of antifilaggrine autoantibodies, as it has the best diagnostic accuracy for the diagnosis of RA. Furthermore, the anti-CCP-ELISA determination in early arthritis is a good predictor of disease persistence and radiographic joint damage. The positivity of Anti-CCP some years before the onset of the RA and the high concentration of autoantibodies in synovial fluid suggest a possible pathogenetic role of citrullination. However, at present, it is unclear whether anti-CCP antibodies have a better diagnostic performance than rheumatoid factor in recent onset synovitis and if they confer any additional value to the prognostic evaluation obtained with validated predictors of outcome (FR, joint count, duration of disease).