micrornas in autoimmune rheumatic diseases

The etiology of autoimmune diseases remains largely unknown. In recent years, besides genetic factors, several studies proposed that the epigenome may hold the key to a better understanding of autoimmunity initiation and perpetuation. More specifically epigenetic regulatory mechanisms comprise DNA methylation, a variety of histone modifications, and microRNA (miRNA) activity, all of which act upon gene and protein expression levels. In particular it is well known that epigenetic mechanisms are important for controlling the pattern of gene expression during development, the cell cycle, and the response to biological or environmental changes. In the present review a description of the most frequent epigenetic deregulations, in particular the role of miRNA, in rheumatic autoimmune disorders will be analyzed

One-year follow-up of mud-bath therapy in patients with bilateral knee osteoarthritis: a randomized, single-blind controlled trial

The objective of this prospective parallel randomized single-blind study was to assess that a cycle of mud-bath therapy (MBT) provides any benefits over usual treatment in patients with bilateral knee osteoarthritis (OA). Patients with symptomatic primary bilateral knee OA, according to ACR criteria, were included in the study and randomized to one of two groups: one group received a cycle of MBT at spa center of Chianciano Terme (Italy) in addition to the usual treatment, and one group continued their regular care routine alone. Clinical assessments were performed 7\ufffddays before enrollment (screening visit), at the time of enrollment (basal time), after 2\ufffdweeks, and after 3, 6, 9, and 12\ufffdmonths after the beginning of the study. All assessments were conducted by two researchers blinded to treatment allocation. The primary efficacy outcomes were the global pain score evaluated by Visual Analog Scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) subscore for physical function (W-TPFS). Of the 235 patients screened, 103 met the inclusion criteria: 53 patients were included in the MBT group and 50 in the control group. In the group of patients treated with MBT, we observed a statistically significant (p\ufffd<\ufffd0.001) reduction of VAS and W-TPFS score at the end of the treatment; this improvement was significant (p\ufffd<\ufffd0.05) also at 3\ufffdmonths of follow-up. The control group did not show significant differences between baseline time and all other times. The differences between one group were significant for both primary parameters already from the 15th day and persisted up to the 9th month. This beneficial effect was confirmed by the significant reduction of symptomatic drug consumption. Tolerability of MBT seemed to be good, with light and transitory side effects. Our results confirm that a cycle of MBT added to usual treatment provides a beneficial effect on the painful symptoms and functional capacities in patients with knee OA that lasts over time. Mud-bath therapy can represent a useful backup to pharmacologic treatment of knee OA or a valid alternative for patients who do not tolerate pharmacological treatments

Viral genotype and HLA class II alleles influence on extra-hepatic manifestations of chronic HCV infection

Objective: To test whether an association between HCV genotype, HLA class II alleles distribution and extra-hepatic manifestations (EHM ) can be demonstrated in a group of Italian patients with chronic HCV infection . Methods: Sixty patients affected by HCV infection with EHM were consecutively enrolled. 163 HCV patients without EHM were tested as controls for the prevalence of HCV genotypes, while we referred to literature as to the controls for HLA distribution. HCV-RNA was quantified by a RT-PCR. HLA class II alleles typing was performed using a standard microlymphocytotoxicity assay. We used chi-square or Fisher test (p<0.05 significant). Odds Ratio (OR) was performed by 2X2 contingency table. Results: HCV 2c genotype was found in 63.46% of patients compared to 19.63% of controls (p<0.0001; OR=7.11). Furthermore, it correlated with carpal tunnel syndrome (p=0.03; OR=4.5) and autoimmune thyroiditis (p=0.02; OR=9.2). On the contrary, 1b genotype protected from EHM in toto (p=0.0004; OR=0.21) and particularly from carpal tunnel syndrome (p=0.0014; OR=0.07). Moreover, 3a genotype prevented HCV people from having cryoglobulinemia (p=0.05; OR=0.11). As to HLA, DR6 seemed to facilitate EHM in HCV patients (p=0.041; OR=1.61), while DQ2 (p=0.03; OR=0.5) and DQ3 (p=0.002; OR= 0.5) may play a protective role. In addition, HLA DR3 was associated with cryoglobulinemia (p=0.02; OR=9.5). Conclusions: According to our findings, 2c genotype can be considered as a major risk factor for developing HCVrelated EHM, while 1b genotype seems to prevent their onset; there are also evidences suggesting that HLA might play a role in chronic HCV infected patients

Serological evidence of human infection with Coxiella burnetii after occupational exposure to aborting cattle

Cattle are broadly deemed a source of Coxiella burnetii; however, evidence reinforcing their role in human infection is scarce. Most published human Q fever outbreaks relate to exposure to small ruminants, notably goats. Anti-phase II C. burnetii IgG and IgM were measured by indirect fluorescent antibody tests in 27 farm and veterinary diagnostic laboratory workers to ascertain whether occupational exposure to cattle aborting due to C. burnetii was the probable source of exposure. Four serological profiles were identified on the basis of anti-phase II IgG and IgM titres. Profile 1, characterised by high IgM levels and concurrent, lower IgG titres (3/27; 11.1%); Profile 2, with both isotypes with IgG titres higher than IgM (2/27; 7.4%); Profile 3 with only IgG phase II (5/27; 18.5%); and Profile 4, in which neither IgM nor IgG were detected (17/27; 63.0%). Profiles 1 and 2 are suggestive of recent C. burnetii exposure, most likely 2.5–4.5 months before testing and, hence, during the window of exposure to the bovine abortions. Profile 3 suggested C. burnetii exposure that most likely predated the window of exposure to aborting cattle, while Profile 4 represented seronegative individuals and, hence, likely uninfected. This study formally linked human Q fever to exposure to C. burnetii infected cattle as a specific occupational hazard for farm and laboratory workers handling bovine aborted material

Erratum to: One-year follow-up of mud-bath therapy in patients with bilateral knee osteoarthritis: a randomized, single-blind controlled trial

The online version of the original article can be found at http://dx.doi.org/ 10.1007/s00484-14-0943-0

Factors Predicting Early Failure of Etanercept in Rheumatoid Arthritis: An Analysis From the Gruppo Italiano di Studio sulla Early Arthritis (Italian Group for the Study of Early Arthritis) Registry

Objectives: This study aims to investigate the factors associated with early discontinuation (within one year) of etanercept (ETA) in rheumatoid arthritis (RA) patients who began ETA as first biologic disease-modifying antirheumatic drug (bDMARD) and who were entered into the Gruppo Italiano di Studio sulla Early Arthritis (Italian Group for the Study of Early Arthritis; GISEA) registry.Patients and methods: This registry-based cohort study included 477 RA patients (95 males, 382 females; median age 53 years; range 18 to 83 years) who began ETA as first bDMARD. Patient demographics, disease features and drugs were re-evaluated after 12 months. Baseline predictors of ETA discontinuation were estimated by univariate and multivariate analyses using Cox regression model.Results: Seventy patients (14.7%) discontinued ETA during the first year (for inefficacy in 55.8%, adverse events in 28.6%, and other reasons in 6.5%). Concurrent conventional synthetic DMARDs (csDMARDs) were reported in 54.3% of patients, mainly methotrexate (MTX), while 52.4% of subjects took low doses of glucocorticoids. Patients stopping ETA more frequently showed one or more comorbidities, mainly cardiovascular diseases (28.6% vs. 15.7% in patients stopping and continuing ETA, respectively, p=0.009). The presence of comorbidities and a combination therapy with csDMARDs other than MTX were independent factors associated with early discontinuation of ETA at multivariate Cox analysis.Conclusion: Although ETA demonstrated a high persistence in biologic-naive RA patients, about 15% of patients discontinued the treatment within 12 months. The presence of comorbidities and a combination therapy with csDMARDs other than MTX were the main factors for an early withdrawal of the drug

Disease: A Hitherto Unexplored Constraint on the Spread of Dogs (Canis lupus familiaris) in Pre-Columbian South America

Although debate continues, there is agreement that dogs (Canis lupus familiaris) were first domesticated in Eurasia, spreading from there to other parts of the world. However, while that expansion already extended as far as Europe, China, and North America by the early Holocene, dogs spread into (and south of) the tropics only much later. In South America, for example, the earliest well attested instances of their presence do not reach back much beyond 3000 cal. BC, and dogs were still absent from large parts of the continent – Amazonia, the Gran Chaco, and much of the Southern Cone – at European contact. Previous explanations for these patterns have focused on cultural choice, the unsuitability of dogs for hunting certain kinds of tropical forest prey, and otherwise unspecified environmental hazards, while acknowledging that Neotropical lowland forests witness high rates of canine mortality. Building on previous work in Sub-Saharan Africa (Mitchell 2015) and noting that the dog’s closest relatives, the grey wolf (C. lupus) and the coyote (C. latrans), were likewise absent from South and most of Central America in Pre- Columbian times, this paper explores instead the possibility that infectious disease constrained the spread of dogs into Neotropical environments. Four diseases are considered, all likely to be native and/or endemic to South America: canine distemper, canine trypanosomiasis, canine rangeliosis, and canine visceral leishmaniasis caused by infection with Leishmania amazonensis and L. colombiensis. The paper concludes by suggesting ways in which the hypothesis that disease constrained the expansion of dogs into South America can be developed further

Treatment strategies for apatient with rheumatoid arthritis and hepatitis C.

BACKGROUND: The poor prognosis of rheumatoid arthritis (RA) can be aggravated by the concomitant presence of chronic hepatitis C virus (HCV) infection and there are no guidelines for the treatment of patients affected by both conditions. OBJECTIVE: To propose new therapeutic strategies for patient affected by RA and concomitant HCV chronic infection. METHODS: Review of the literature on the usage of cyclosporine-A (CsA) and anti-tumour-necrosis-factor (TNF)-alpha agents for the treatment of patients affected by RA and HCV. RESULTS/CONCLUSION: CsA exerts an inhibitory effect on HCV replication and it is safe in patients affected by RA and HCV. Anti-TNF-alpha agents are safe and efficacious in patient with RA and HCV. Anti-TNF-alpha and CsA can be safely given in combination in RA patients with HCV infection

Combination therapy with cyclosporine A and anti-TNF-alpha agents in the treatment of rheumatoid arthritis and concomitant hepatitis C virus infection

We describe two cases of rheumatoid arthritis (RA) patients and concomitant hepatitis C virus infection (HCV), treated with cyclosporine A (CsA) and anti-TNF-alpha agents. SGOT/SGPT and HCV-RNA serum levels remained unchanged longer than 1 year of treatment. No side effects were registered. We suggest that combination therapy with CsA and TNF-alpha blockers should be considered safe and well-tolerated in the treatment of HCV-positive RA patients

Treatment strategies for a patient with rheumatoid arthritis and hepatitis C.

BACKGROUND: The poor prognosis of rheumatoid arthritis (RA) can be aggravated by the concomitant presence of chronic hepatitis C virus (HCV) infection and there are no guidelines for the treatment of patients affected by both conditions.OBJECTIVE: To propose new therapeutic strategies for patient affected by RA and concomitant HCV chronic infection.METHODS: Review of the literature on the usage of cyclosporine-A (CsA) and anti-tumour-necrosis-factor (TNF)-alpha agents for the treatment of patients affected by RA and HCV.RESULTS/CONCLUSION: CsA exerts an inhibitory effect on HCV replication and it is safe in patients affected by RA and HCV. Anti-TNF-alpha agents are safe and efficacious in patient with RA and HCV. Anti-TNF-alpha and CsA can be safely given in combination in RA patients with HCV infection