R. Scrivo

Anti-tumour necrosis factor (TNF) α treatment of rheumatoid arthritis (infliximab) selectively down regulates the production of interleukin (IL) 18 but not of IL12 and IL13

Objective: To measure interleukin (IL)18 serum concentrations in patients with rheumatoid arthritis (RA) undergoing infliximab treatment (tumour necrosis factor (TNF) α blockade) and to evaluate the concomitant modification of IL12 and IL13 serum concentrations, two cytokines belonging to the Th1 and Th2 profile respectively and biologically related to IL18. Methods: Ten patients with RA not responding to disease modifying antirheumatic drugs (DMARDs) received intravenous infliximab at a dose of 3 mg/kg at baseline and after two and six weeks. Serum samples were collected from all patients before each infusion and assayed for IL18, IL12, and IL13 by enzyme linked immunosorbent assay (ELISA); IL18 was also measured eight weeks after the last infusion. Results: Serum concentrations of IL18 in all patients were already markedly reduced from baseline after two weeks (p<0.005). Serum IL18 was also decreased in a stable manner after six (p<0.01) and 14 weeks (p<0.01) compared with baseline concentrations. No significant modifications were found in serum concentrations of IL12 and IL13 at any time point. Conclusion: There was a rapid and persistent decrease in serum concentrations of IL18 in all the patients studied. This result provides evidence of an in vivo regulation of IL18 by TNFα and suggests that anti-TNFα therapy is likely to interrupt the synergistic effect between these two cytokines.

The Immunology of Rheumatoid Arthritis

Abstract:u2002 Rheumatoid arthritis (RA) is represents the most common chronic inflammatory joint disease and is still a major medical challenge because of unsolved issues related to the etiologic and pathogenetic questions. Intensive research has been conducted over the last years that focused on the inappropriate activation of the immune system: although T cells have long been deemed to play a central role in the origin and propagation of joint inflammation, data accumulated so far have widened this perspective recognizing the contribution of other cells, as well as the major histocompatibility complex class II proteins and a composite set of costimulatory signals responsible for the production of proinflammatory cytokines and other soluble mediators implicated in tissue destruction typical of the disease. This paper will provide an insight into the immune system in RA, dissecting cellular and humoral aspects both in serum and in synovium of patients.

Nailfold capillaroscopy changes in systemic lupus erythematosus : correlations with disease activity and autoantibody profile

In systemic lupus erythematosus (SLE) nailfold capillaroscopy (NC) studies have described many different nonspecific patterns. We decided to evaluate NC changes in 44 SLE patients, comparing them with the main clinical, demographic and laboratory parameters, thus to define the real role for NC and its abnormalities in the management of this disease. Fifteen patients (34%) complained of Raynaud’s phenomenon; nine of them (20%) showed relevant capillaroscopic changes (capillaroscopic score >1). In details: three patients (6.8%) had loss of capillaries, while 18 (41%) had a capillary length variability, 16 (36.5%) showing shorter and two (4.5%) longer capillaries; tortuous, meandering, bizarre, ramified and/or bushy capillaries were found in 26 (59%), seven (16%), two (4.5%), three (7%) cases, respectively. An irregular distribution of the capillary array was present in six cases (14%) while microhaemorrhages were found in four cases (9%). 4 patients (9%) showed enlarged capillaries and changes of blood flow. A capillaroscopic score >1 was more frequently associated with higher ECLAM (P < 0.005) and SLEDAI (P < 0.01) activity scores, with the presence of anti-cardiolipin (P < 0.04) and anti-Sm (P < 0.04) antibodies, and also with the presence (P < 0.04) and higher titer (P < 0.001) of anti-dsDNA antibodies. No statistically significant correlation was found among the different capillaroscopy findings, age, disease duration, or treatment, nor with any clinical manifestation of the disease, such as cutaneous, renal or neurological. Our findings confirm the importance of the microvascular involvement in SLE. The NC abnormalities seem to be related to the disease activity and to the presence of many different antibodies, highly involved in the expression of SLE. NC proved to be an easy-to-perform noninvasive technique, able to achieve useful data to better evaluate such a pleomorphic disease as SLE.

Life-table analysis of etanercept with or without methotrexate in patients with psoriatic arthritis

The recent analysis of data included in the Stockholm TNFα Follow- Up (STURE) registry showed that the concomitant use of methotrexate (MTX) with etanercept (ETN), adalimumab or infliximab was associated with long-term drug survival of anti-tumour necrosis factor (TNF) agents in patients with psoriatic arthritis (PsA).1 The positive effect of MTX was primarily linked to fewer drop-outs due to adverse events.1 This analysis did not consider each anti-TNF drug subgroup. For this reason we determined the cumulative probability of taking ETN with or without MTX in a large cohort of patients.nnWe prospectively studied 82 patients, admitted to our rheumatological unit since 2001, affected by PsA, classified …

Distribution of interleukin‐10 family cytokines in serum and synovial fluid of patients with inflammatory arthritis reveals different contribution to systemic and joint inflammation

Evidence exists that interleukin (IL)‐10 family cytokines may be involved in the pathogenesis of rheumatoid arthritis (RA). We sought to determine whether or not these cytokines are involved in psoriatic arthritis (PsA). We conducted a prospective study on patients with PsA, RA and osteoarthritis (OA); healthy controls (HC) were also included. We analysed IL‐20, IL‐24 and IL‐19 serum and synovial fluid (SF) levels and change of serum levels following treatment with biological agents. IL‐20 serum levels were increased in PsA and RA compared with OA patients and HC and with matched SF levels. IL‐24 serum levels in PsA, RA and OA patients were higher than those in HC and also with respect to matched SF in PsA. IL‐19 serum levels were higher in HC and OA compared with PsA and RA patients; IL‐19 SF levels were higher in PsA and RA compared with OA patients, and in PsA compared with RA patients. PsA and RA patients showed a reduction of IL‐19 serum levels after biological treatment. Therefore, IL‐19 seems to be involved mainly in the joint inflammation, whereas IL‐20 and IL‐24 appear to participate mainly in the systemic responses. These findings may further the comprehension of the contribution of these cytokines to the inflammatory response involved in chronic arthritis, as well as to the development of novel therapeutic strategies.

Autoantibody Production in Anti‐TNF‐α‐Treated Patients

Abstract:u2002 Targeting tumor necrosis factor alpha (TNF‐α) has offered an additional therapeutic strategy against several rheumatic inflammatory disorders. The current use of TNF‐α inhibitors allows physicians who manage these diseases and patients themselves to testify to an extraordinary efficacy, even though caution for possible adverse events must be maintained. Among these, the occurrence of autoimmune phenomena, encompassing new autoantibody formation and triggering of clinical manifestations, continues to be noted in published reports. Here, we review the current knowledge regarding the autoimmune phenomena linked to anti‐TNF‐α therapy in patients with rheumatic inflammatory disorders.

Relationship of interleukin-12 and interleukin-13 imbalance with class-specific rheumatoid factors and anticardiolipin antibodies in systemic lupus erythematosus.

Abstractu2002The aim of the study was to evaluate whether the imbalance between IL-12 and IL-13 serum levels, reflecting Th1/Th2 activity, is related to class-specific circulating rheumatoid factors (RF) and anticardiolipin (aCL) antibodies in SLE. Using ELISA we measured serum IL-12, IL-13, RF and aCL antibodies in 73 SLE patients and 20 healthy controls. The determination of IL-12/IL-13 ratio showed that IL-12 levels were above (group A), equal to (group B) or below (group C) IL-13 levels in 71.2%, 15.1% and 13.7% of SLE patients, respectively. IgM-RF levels were significantly higher in group C than in groups A (P < 0.002) and B (P < 0.019). Group C had also higher IgM-aCL levels than group A (P < 0.04). No relationship between IL-12/IL-13 ratio and clinical or other laboratory parameters was found. It was concluded that the increased levels of both IgM-RF and IgM-aCL in patients with prevalent Th2 activity suggest that the predominance of Th2 over Th1 could drive autoantibody production in SLE patients.

Porphyromonas gingivalis in the tongue biofilm is associated with clinical outcome in rheumatoid arthritis patients

Several studies have suggested a link between human microbiome and rheumatoid arthritis (RA) development. Porphyromonas gingivalis seems involved in RA initiation and progression, as supported by the high occurrence of periodontitis. In this case–control study, we analysed tongue P. gingivalis presence and quantification in a large healthy and RA cohort. We enrolled 143 RA patients [male/female (M/F) 32/111, mean ± standard deviation (s.d.), age 57·5 ± 19·8 years, mean ± s.d. disease duration 155·9 ± 114·7 months); 36 periodontitis patients (M/F 11/25, mean ± s.d., age 56 ± 9·9 years, mean ± s.d. disease duration 25·5 ± 20·9 months); and 57 patients (M/F 12/45, mean ± s.d., age 61·4 ± 10·9 years, mean ± s.d. disease duration 62·3 ± 66·9 months) with knee osteoarthritis or fibromyalgia. All subjects underwent a standard cytological swab to identify the rate of P. gingivalis/total bacteria by using quantitative real‐time polymerase chain reaction. The prevalence of P. gingivalis resulted similarly in RA and periodontitis patients (48·9 versus 52·7%, P = not significant). Moreover, the prevalence of this pathogen was significantly higher in RA and periodontitis patients in comparison with control subjects (P = 0·01 and P = 0·003, respectively). We found a significant correlation between P. gingivalis rate in total bacteria genomes and disease activity score in 28 joints (DAS28) (erythrocyte sedimentation rate) (r = 0·4, P = 0·01). RA patients in remission showed a significantly lower prevalence of P. gingivalis in comparison with non‐remission (P = 0·02). We demonstrated a significant association between the percentage of P. gingivalis on the total tongue biofilm and RA disease activity (DAS28), suggesting that the oral cavity microbiological status could play a role in the pathogenic mechanisms of inflammation, leading to more active disease.

FRI0045 Oral microbiome profile in rheumatoid arthritis patients: association between tongue biofilm porphyromonas gingivalis amount and disease activity

Background P. gingivalis is a Gram-negative anaerobic bacterium usually located in the oral cavity, as component of microbiome. Next to the established association with oral cavity diseases, such as periodontitis and halitosis, in the last years a growing interest has been addressed to its implication in the development of autoimmune diseases, such as Rheumatoid Arthritis (RA). The ability of P. gingivalis to citrullinate peptides is the most relevant link with RA. Indeed, this bacterium has several virulence factors directly contributing to its chronic inflammation regardless of citrullination. Data from the literature demonstrated the ability of P. gingivalis in inducing the production of several inflammatory cytokines, such as TNF, IL6 and IL17, through the TLR signaling pathways. Objectives In the present case-control study, we aimed at analysing tongue microbiome in a large RA cohort, focusing on the evaluation of P. gingivalis presence and quantification. Methods We enrolled 143 RA patients (1987 ACR criteria; M/F 32/111, mean±SD age 57.5±19.8 years, mean±SD disease duration 155.9±114.7 months); 36 periodontitis (M/F 11/25, mean±SD age 56±9.9 years, mean±SD disease duration 25.5±20.9 months); 57 (M/F 12/45, mean ±SD age 61.4±10.9 years, mean ±SD disease duration 62.3±66.9 months) affected by knee osteoarthritis or fibromyalgia (control subjects – CS). All subjects underwent a clinical evaluation in order to assess disease activity by DAS28. Blood serum samples were obtained to evaluate the presence of ACPA by a commercial ELISA kit. Finally, a standard cytologic swab to collect tongue biofilm samples was performed and the presence of P. gingivalis was evaluated by PCR method. Results The prevalence of P. gingivalis resulted significantly higher in RA and PD patients in comparison with CS (P=0.01 and P=0.003, respectively). No correlation between bacterium presence and ACPA was found. When evaluating the percentage of P. gingivalis on the total tongue biofilm, we observed a significant correlation between this measure and DAS28 values (r=0.4, P=0.01). Furthermore, RA patients in DAS28 remission showed a significantly lower prevalence of P. gingivalis in comparison with non-remission patients (P=0.02). Conclusions In the present study, for the first time we assessed the prevalence of P. gingivalis, i.e. its percentage on the total tongue biofilm, in a large RA cohort. A significant correlation between the amount of P. gingivalis on total tongue biofilm and disease activity was observed. There was no association with ACPA, suggesting that this bacterium, beyond citrullination, could be implicated in triggering a pro-inflammatory state in RA. Disclosure of Interest None declared