Up to 30-50% of patients with locally advanced prostate cancer (PCa) undergoing radiotherapy (RT) experience biochemical recurrence (BCR). The immune system affects the RT response. Immunogenetics ...could define new biomarkers for personalization of PCa patients' treatment. The aim of this study is to define the immunogenetic biomarkers of 10 year BCR (primary aim), 10 year overall survival (OS) and 5 year BCR (secondary aims). In this mono-institutional retrospective study, 549 Caucasian patients (a discovery set
= 418; a replication set
= 131) were affected by locally advanced PCa and homogeneously treated with RT. In the training set, associations were made between 447 SNPs in 77 genes of the immune system; and 10 year BCR and 10 year OS were tested through a multivariate Cox proportional hazard model. Significant SNPs (
-value < 0.05,
-value < 0.15) were analyzed in the replication set. Replicated SNPs were tested for 5 year BCR in both sets of patients. A polymorphism in the
gene (rs4143815) was the unique potential genetic variant of 10 year BCR (training set:
= 0.003, HR (95% CI) = 0.58 (0.41-0.83); replication set:
= 0.063, HR (95% CI) = 0.52 (0.26-1.04)) that was significantly associated with 5 year BCR (training set:
= 0.009, HR (95% CI) = 0.59 (0.40-0.88); replication set:
= 0.036, HR (95% CI) = 0.39 (0.16-0.94)). No biomarkers of OS were replicated. rs4143815-
arose as a new immunogenetic biomarker of BCR in PCa, giving new insights into the RT/immune system interaction, which could be potentially useful in new approaches using anti-PDL1 therapies for PCa.
Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease resulting from the inflammatory infiltration of exocrine glands, mainly salivary and lacrimal glands, leading to secretory dysfunction ...and serious complications including debilitating fatigue, systemic autoimmunity, and lymphoma. Like other autoimmune disorders, a strong interferon (IFN) signature is present among subsets of pSS patients, suggesting the involvement of innate immunity in pSS pathogenesis.
/NKp30 is a natural killer (NK) cell-specific activating receptor regulating the cross talk between NK and dendritic cells including type II IFN secretion upon NK-cell activation. A genetic association between single-nucleotide polymorphisms (SNPs) in the
/NKp30 promoter gene and a higher susceptibility for pSS has been previously described, with pSS patients most frequently carrying the major allele variant associated with a higher NKp30 transcript and IFN-γ release as a consequence of the receptor engagement. In the present study, we combined RNA-sequencing and histology from pSS salivary gland biopsies to better characterize NKp30 (
) and its ligand B7/H6 (
) in pSS salivary gland tissues. Levels of
/NKp30 were significantly increased both in salivary glands and in circulating NK cells of pSS patients compared with sicca controls, especially in salivary glands with organized ectopic lymphoid structures. In line with this observation, a strong correlation between
/NKp30 levels and salivary gland infiltrating immune cells (CD3, CD20) was found. Furthermore,
/NKp30 levels also correlated with higher IFN-γ, Perforin, and Granzyme-B expression in pSS SGs with organized ectopic lymphoid structures, suggesting an activation state of NK cells infiltrating SG tissue. Of note, NKp30+ NK cells accumulated at the border of the inflammatory
, while the NKp30 ligand, B7/H6, is shown to be expressed mainly by ductal epithelial cells in pSS salivary glands. Finally, immunomodulatory treatment, such as the B-cell depleting agent rituximab, known to reduce the infiltration of immune cells in pSS SGs, prevented the upregulation of
/NKp30 within the glands.
We aimed to validate the association of 28 GWAS-identified genetic variants for response to TNF inhibitors (TNFi) in a discovery cohort of 1361 rheumatoid arthritis (RA) patients monitored in routine ...care and ascertained through the REPAIR consortium and DANBIO registry. We genotyped selected markers and evaluated their association with response to TNFi after 6 months of treatment according to the change in disease activity score 28 (ΔDAS28). Next, we confirmed the most interesting results through meta-analysis of our data with those from the DREAM cohort that included 706 RA patients treated with TNFi. The meta-analysis of the discovery cohort and DREAM registry including 2067 RA patients revealed an overall association of the
SNP with a lower improvement in DAS28 that remained significant after correction for multiple testing (per-allele OR
=0.83,
=0.000077;
=0.61). In addition, we found that each copy of the
allele was significantly associated with lower improvement in DAS28 in rheumatoid factor (RF)-positive patients (per-allele OR
=0.67,
=0.00058;
=0.06) whereas an opposite but not significant effect was detected in RF-negative subjects (per-allele OR
=1.38,
=0.10;
=0.45;
=0.00028). Interestingly, although the identified associations did not survive multiple testing correction, the meta-analysis also showed overall and RF-specific associations for the
and
SNPs with decreased changes in DAS28 (per-allele OR
= 0.85,
=0.0059;
=0.63 and OR
=0.81,
=0.0059;
=0.69 and OR
=1.00,
=0.99;
=0.12;
=0.032). Mechanistically, we found that subjects carrying the
allele had significantly increased numbers of CD45RO+CD45RA+ T cells (
=0.000025) whereas carriers of the
genotype showed significantly increased levels of soluble scavengers CD5 and CD6 in serum (
=0.00037 and
=0.00041). In addition, carriers of the
allele showed decreased production of IL6 after stimulation of PBMCs with
and
bacteria (
=0.00046 and
=0.00044), which suggested a reduced IL6-mediated anti-inflammatory effect of this marker to worsen the response to TNFi. In conclusion, this study confirmed the influence of the
and
loci to determine the response to TNFi in RA patients and suggested a weak effect of the
loci that need to be further investigated.
ObjectiveTo perform a systematic literature review (SLR) on different outcomes of remote care compared with face-to-face (F2F) care, its implementation into clinical practice and to identify drivers ...and barriers in order to inform a task force formulating the EULAR Points to Consider for remote care in rheumatic and musculoskeletal diseases (RMDs).MethodsA search strategy was developed and run in Medline (PubMed), Embase and Cochrane Library. Two reviewers independently performed standardised data extraction, synthesis and risk of bias (RoB) assessment.ResultsA total of 2240 references were identified. Forty-seven of them fulfilled the inclusion criteria. Remote monitoring (n=35) was most frequently studied, with telephone/video calls being the most common mode of delivery (n=30). Of the 34 studies investigating outcomes of remote care, the majority addressed efficacy and user perception; 34% and 21% of them, respectively, reported a superiority of remote care as compared with F2F care. Time and cost savings were reported as major benefits, technical aspects as major drawback in the 13 studies that investigated drivers and barriers of remote care. No study addressed remote care implementation. The main limitation of the studies identified was the heterogeneity of outcomes and methods, as well as a substantial RoB (50% of studies with high RoB).ConclusionsRemote care leads to similar or better results compared with F2F treatment concerning efficacy, safety, adherence and user perception outcomes, with the limitation of heterogeneity and considerable RoB of the available studies.
Patients with connective tissue diseases can develop interstitial lung disease (ILD), leading to a progressive fibrosing ILD (PF-ILD) phenotype in some cases. We aimed to investigate the occurrence ...of PF-ILD in idiopathic inflammatory myopathies (IIMs), and factors potentially predicting this phenotype. Secondary aims were to assess the radiological pattern and factors associated with IIMs-ILD.
Patients with IIMs from our multicentric prospective cohort were retrospectively evaluated. Data were recorded at IIMs and ILD diagnosis, and during follow-up. Patients with ILD were classified according to the predominant high-resolution CT (HRCT) pattern: non-specific interstitial pneumonia (NSIP), usual interstitial pneumonia (UIP) and organising pneumonia (OP). PF-ILD was defined according to the 2022 American Thoracic Society (ATS), European Respiratory Society (ERS), Japanese Respiratory Society (JRS) and Latin American Thoracic Society (ALAT) guidelines. Univariate and multivariate analyses were performed to identify factors associated to ILD and to PF-ILD.
Of 253 patients with IIMs, 125 (49%) had ILD: 99 (78%) at IIMs diagnosis and 26 (22%) during follow-up (21/26 within 5 years). Multivariate analysis identified anti-Jo-1, anti-MDA5, anti-Ro52, high score on manual muscle test, mechanic's hands and Raynaud's phenomenon as independently associated with ILD. The predominant HRCT pattern was NSIP (50% of patients), followed by UIP (28%) and OP (22%). At 1-year follow-up, PF-ILD occurred in 18% of IIMs-ILD. PF-ILD was predicted by anti-MDA5, heliotropic rash, xerostomia and xerophthalmia at univariate but not at multivariate analysis.
Patients with IIM should be carefully screened for ILD at IIMs diagnosis and yearly during follow-up. All patients with IIMs-ILD should be carefully monitored to capture ILD progression since a consistent proportion of them are expected to develop PF-ILD.
Hepatitis B (HBV) infection, which is prevalent worldwide, is also frequently seen in patients with rheumatoid arthritis (RA). The Italian Society of Rheumatology (SIR) and the Italian Society of ...Infectious and Tropical Diseases (SIMIT) endorsed a national consensus process to review the available evidence on HBV management in RA patients and to produce practical, hospital-wide recommendations.
The consensus panel consisted of infectious disease consultants, rheumatologists and epidemiologists and used the criteria of the Oxford Center for Evidence-based Medicine to assess the quality of the evidence and the strength of their recommendations.
A core-set of statements has been developed to help clinicians in the management of patients with RA and HBV infection. Vaccination and prophylaxis of RA patients treated with biological drugs have been also discussed.
HBV infection is not rare in clinical practice; a screening for HBV in all patients with early arthritis is not universally accepted, while it is considered mandatory before starting any immunosuppressive or hepatotoxic treatment. In fact, a specific risk, associated with the use of biologic treatments, exists for patients with HBV infection, although longitudinal studies of viral reactivation are generally reassuring. RA patients with HBV infection should be referred to the hepatologist and correctly classified into active or inactive carriers. Patients with active hepatitis B should undergo antiviral treatment before starting immunosuppressive treatments. Occult HBV carriers should be monitored or receive prophylaxis on the basis of the risk of reactivation associated with the administered treatment.
Psoriasis (PsO) and Psoriatic Arthritis (PsA) are chronic, immune-mediated diseases that share common etiopathogenetic pathways. Up to 30% of PsO patient may later develop PsA. In nearly 75% of ...cases, skin psoriatic lesions precede arthritic symptoms, typically 10 years prior to the onset of joint symptoms, while PsO diagnosis occurring after the onset of arthritis is described only in 15% of cases. Therefore, skin involvement offers to the rheumatologist a unique opportunity to study PsA in a very early phase, having a cohort of psoriatic “risk patients” that may develop the disease and may benefit from preventive treatment. Progression from PsO to PsA is often characterized by non-specific musculoskeletal symptoms, subclinical synovio-entheseal inflammation, and occasionally asymptomatic digital swelling such as painless toe dactylitis, that frequently go unnoticed, leading to diagnostic delay. The early diagnosis of PsA is crucial for initiating a treatment prior the development of significant and permanent joint damage. With the ongoing development of pharmacological treatments, early interception of PsA has become a priority, but many obstacles have been reported in daily routine. The introduction of digital technology in rheumatology may fill the gap in the physician-patient relationship, allowing more targeted monitoring of PsO patients. Digital technology includes telemedicine, virtual visits, electronic health record, wearable technology, mobile health, artificial intelligence, and machine learning. Overall, this digital revolution could lead to earlier PsA diagnosis, improved follow-up and disease control as well as maximizing the referral capacity of rheumatic centers.
To evaluate humoral and T-cell cellular-mediated immune response after three doses of SARS-CoV-2 mRNA vaccines in patients with systemic lupus erythematosus (SLE) under Belimumab.
12 patients on ...Belimumab and 13 age-matched healthy volunteers were recruited. Patients were in remission or in low disease activity, and they were taking no corticosteroids or only low doses. None of the patients and controls had detectable anti-SARS-CoV-2 antibodies due to previous exposure to the virus. All the patients received three doses of mRNA anti-SARS-CoV-2 vaccines and the humoral and cellular-mediated response were tested 4 weeks after the second dose (T0), 6 months after the second dose (T1) and 4 weeks after the third dose (T2). Comparison with the control group was performed at time T0 (i.e., 4 weeks after the second dose). Total anti-SARS-CoV-2 RBD antibodies were analyzed using a diagnostic assay, while cellular-mediated response was evaluated using the interferon-gamma release assay (IGRA).
A humoral response was documented in all the patients at T0 (median 459; IQR 225.25-758.5), but the antibody titer significantly declined from T0 to T1 (median 44.7; IQR: 30.3-202;
= 0.0066). At T2, the antibody titer significantly increased from T1 (median 2500; IQR: 2500-2500), and it was not different from T0 (respectively
< 0.0001,
= 0.66). Cellular-mediated response significantly declined from T0 to T1 (
= 0.003) but not from T0 to T2 (
= 0.3). No differences were found between patients and controls at T0 as regards both humoral and cellular responses (
= 1.0 and
= 0.09 for humoral and cellular responses, respectively).
The third dose of mRNA COVID-19 vaccine can restore both humoral and cellular immune response in SLE patients on Belimumab.
ObjectiveSubjects with subclinical psoriatic arthritis (PsA), defined as the presence of arthralgia in psoriasis (PsO), are at higher risk of PsA but scant real-world data exist. Our aims were to (1) ...estimate the probability of PsA development in subclinical PsA, (2) characterise subclinical PsA symptoms and (3) determine the clinical patterns at PsA diagnosis.MethodsPatients with PsO, mainly subclinical PsA, were evaluated longitudinally in two European cohorts. The key outcome was new-onset PsA. Musculoskeletal symptoms including inflammatory and non-inflammatory symptoms before PsA diagnosis were collected. Occurrence of PsA was analysed with survival analysis and cumulative incidence functions (CIFs).Results384 patients with PsO were included with a mean follow-up of 33.0 (±20.9) months. 311 of 384 (80.9%) had subclinical PsA with a PsA incidence rate of 7.7 per 100 patient-years. Subclinical PsA displayed a higher risk of PsA development compared with PsO (HR=11.7 (95% CI 1.57 to 86.7), p=0.016). The probability of new-onset PsA estimated by the CIF was 9.4% (95% CI 4.7% to 10.6%) at month 12 and 22.7% (95% CI 17.2% to 28.6%) at month 36. 58.9% of cases reported inflammatory symptoms in the months immediately prior to PsA diagnosis but prior non-inflammatory symptoms were evident in 83.9% prior to PsA diagnosis. Peripheral joint swelling was the predominant PsA presentation pattern (82.1%).ConclusionsThe probability of PsA development among subclinical PsA was relatively high, emphasising the importance of emergent musculoskeletal symptoms when aiming for PsA prevention. Joint swelling was the dominant feature in new-onset PsA, likely reflecting clinical confidence in recognising joint swelling.
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