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Porto-sinusoidal vascular disorder (PSVD) encompasses a group of vascular disorders characterized by lesions of the portal venules and sinusoids with clinical manifestations ranging from non-specific abnormalities in serum liver enzymes to clinically overt portal hypertension and related complications. Several reports have documented cases of PSVD in patients with systemic autoimmune conditions, such as systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. It is of note that these diseases share specific pathophysiological features with PSVD, including endothelial dysfunction, vascular inflammation, and molecular signatures. This narrative review aims to summarize the current knowledge on the association between PSVD and systemic autoimmune diseases, emphasizing the importance of promptly recognizing this condition in the rheumatological practice, and highlighting the key aspects where further research is necessary from both pathogenic and clinical perspectives., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Disease-specific autoantibodies are considered the most important biomarkers for systemic sclerosis (SSc), due to their ability to stratify patients with different severity and prognosis. Anti-nuclear antibodies (ANA), occurring in subjects with isolated Raynuad's phenomenon, are considered the strongest independent predictors of definite SSc and digital microvascular damage, as observed by nailfold videocapillaroscopy. ANA are present in more than 90% of SSc, but ANA negativity does not exclude SSc diagnosis: a little rate of SSc ANA negative exists and shows a distinct subtype of disease, with less vasculopathy, but more frequent lower gastrointestinal involvement and severe disease course. Anti-centromere, anti-Th/To, and anti-Topoisomerase I antibodies could be considered as classical biomarkers, covering about 60% of SSc and defining patients with well-described cardio-pulmonary complications. In particular, anti-Topoisomerase I represent a risk factor for development of diffuse cutaneous involvement and digital ulcers in the first 3 years of disease, as well as severe interstitial lung disease (ILD). Anti-RNA polymerase III is a biomarker with new clinical implications: very rapid skin thickness progression, gastric antral vascular ectasia, the occurrence of synchronous cancers, and possible association with silicone breast implants rupture. Moreover, novel SSc specific autoantibodies have been globally described in about 10% of "seronegative" SSc patients: anti-elF2B, anti-RuvBL1/2 complex, anti-U11/U12 RNP, and anti-BICD2 depict specific SSc subtypes with severe organ complications. Many autoantibodies could be considered markers of overlap syndromes, including SSc. Anti-Ku are found in 2-7% of SSc, strictly defining the PM/SSc overlap. They are associated with synovitis, joint contractures, myositis, and negatively associated with vascular manifestation of disease. Anti-U3RNP are associated with a well-defined clinical phenotype: Afro-Caribbean male patients, younger at diagnosis, and higher risk of pulmonary hypertension and gastrointestinal involvement. Anti-PM/Scl define SSc patients with high frequency of ILD, calcinosis, dermatomyositis skin changes, and severe myositis. The accurate detection of autoantibodies SSc specific and associated with overlap syndromes is crucial for patients' stratification. ANA should be correctly identified using indirect immunofluorescent assay and a standardized way of patterns' interpretation. The gold-standard technique for autoantibodies' identification in SSc is still considered immunoprecipitation, for its high sensitivity and specificity, but other assays have been widely used in routine practice. The identification of SSc autoantibodies with high diagnostic specificity and high predictive value is mandatory for early diagnosis, a specific follow-up and the possible definition of the best therapy for every SSc subsets. In addition, the validation of novel autoantibodies is mandatory in wider cohorts in order to restrict the gap of so-called seronegative SSc patients., (© 2022. The Author(s).)

Nucleolar staining is one of the standard patterns in immunofluorescence antinuclear antibodies (ANA), seen in 5-9% of ANA in various conditions. Antinucleolar antibodies (ANoA) are classified into 3 patterns in the International Consensus on ANA Patterns (ICAP) classification; AC-8 homogeneous pattern, AC-9 clumpy pattern, and AC-10 punctate pattern. Specificities known to show AC-8 include anti-Th/To, -PM-Scl, -nucleophosmin/B23, -nucleolin/C23, -No55, and others. AC-9 is seen by anti-fibrillarin/U3RNP and AC-10 by anti-RNA polymerase I and hUBF/NOR-90. ANoA has been classically known to be associated with scleroderma (SSc) and the characterization of nucleolar antigens identified several autoantigens recognized by SSc autoantibodies. The clinical association of anti-Th/To, PM-Scl, fibrillarin/U3RNP, and RNA polymerase I with SSc or SSc-overlap syndrome is well established, and commercial assays are developed. Anti-hUBF/NOR90, nucleophosmin/B23, and nucleolin/C23 are known for decades and reported in systemic autoimmune rheumatic diseases (SARDs), malignancies, graft versus host disease (GVHD), and others; however, their clinical significance remains to be established., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: The SARS-CoV-2 infection has been advocated as an environmental trigger for autoimmune diseases, and a paradigmatic example comes from similarities between COVID-19 and the myositis-spectrum disease associated with antibodies against the melanoma differentiation antigen 5 (MDA5) in terms of clinical features, lung involvement, and immune mechanisms, particularly type I interferons (IFN)., Case Report: We report a case of anti-MDA5 syndrome with skin manifestations, constitutional symptoms, and cardiomyopathy following a proven SARS-CoV-2 infection., Systematic Literature Review: We systematically searched for publications on inflammatory myositis associated with COVID-19. We describe the main clinical, immunological, and demographic features, focusing our attention on the anti-MDA5 syndrome., Discussion: MDA5 is a pattern recognition receptor essential in the immune response against viruses and this may contribute to explain the production of anti-MDA5 antibodies in some SARS-CoV-2 infected patients. The activation of MDA5 induces the synthesis of type I IFN with an antiviral role, inversely correlated with COVID-19 severity. Conversely, elevated type I IFN levels correlate with disease activity in anti-MDA5 syndrome. While recognizing this ia broad area of uncertainty, we speculate that the strong type I IFN response observed in patients with anti-MDA5 syndrome, might harbor protective effects against viral infections, including COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tonutti, Motta, Ceribelli, Isailovic, Selmi and De Santis.)

The concern about the offspring's health is one of the reasons for a reduced family size of women with rheumatic diseases (RD). Increased risk of autoimmune diseases (AD) and neurodevelopmental disorders (ND) has been reported in children born to patients with RD. Within a nationwide survey about reproductive issues of women with RD, we aimed at exploring the long-term outcome of their children. By surveying 398 patients who received their diagnosis of RD during childbearing age (before the age of 45), information about the offspring were obtained from 230 women who declared to have had children. A total of 148 (64.3%) patients were affected by connective tissue diseases (CTD) and 82 (35.7%) by chronic arthritis. Data on 299 children (156 males, 52.1%; mean age at the time of interview 17.1 ± 9.7 years) were collected. Twelve children (4.0%), who were born to patients with CTD in 75% of the cases, were affected by AD (8 cases of celiac disease). Eleven children had a certified diagnosis of ND (3.6%; 6 cases of learning disabilities); 9 of them were born to mothers with CTD (5 after maternal diagnosis). No association was found between ND and prenatal exposure to either maternal autoantibodies or anti-rheumatic drugs. Absolute numbers of offspring affected by AD and ND were low in a multicentre cohort of Italian women with RD. This information can be helpful for the counselling about reproductive issues, as the health outcomes of the offspring might not be an issue which discourage women with RD from having children., (© 2021. The Author(s).)

Objective: The reproductive choices of women affected by rheumatic diseases (RD) can be influenced by several factors, including the quality of physician-patient communication. We conducted a survey on reproductive issues aiming at exploring the unmet needs of women with RD during childbearing age., Methods: We administered 65 multiple-choice and 12 open-answer questions about pregnancy counselling, contraception, use of drugs during pregnancy and other women reproductive issues to 477 consecutive women with RD aged 18-55 years followed-up in 24 rheumatology centres in Italy. Analysis was restricted to 398 patients who received their diagnosis of RD before the age of 45. According to the RD diagnosis, patients were subdivided into 2 groups: connective tissue diseases (n = 249) and chronic arthritis (n = 149)., Results: At the time of interview, women in both groups had a mean age of 40 years. Nearly one third of patients in each group declared not to have received any counselling about either pregnancy desire nor contraception. A smaller family size than desired was reported by nearly 37% of patients, because of concerns related to maternal disease in one fourth of the cases. A "Disease Knowledge Index" (DKI) was created to investigate the degree of patients' information about the implications of their RD on reproductive issues. Having received counselling was associated with higher DKI values and with a positive impact on family planning., Conclusion: Italian women of childbearing age affected by RD reported several unmet needs in their knowledge about reproductive issues. Strategies are needed to implement and facilitate physician-patient communication., (Copyright © 2018. Published by Elsevier Masson SAS.)

Autoimmunity and chronic inflammation recognize numerous shared factors and, as a result, the resulting diseases frequently coexist in the same patients or respond to the same treatments. Among the convenient truths of autoimmune and chronic inflammatory diseases, there is now agreement that these are complex conditions in which the individual genetic predisposition provides a rate of heritability. The concordance rates in monozygotic and dizygotic twins allows to estimate the weight of the environment in determining disease susceptibility, despite recent data supporting that only a minority of immune markers depend on hereditary factors. Concordance rates in monozygotic and dizygotic twins should be evaluated over an observation period to minimize the risk of false negatives and this is well represented by type I diabetes mellitus. Further, concordance rates in monozygotic twins should be compared to those in dizygotic twins, which share 50% of their genes, as in regular siblings, but also young-age environmental factors. Twin studies have been extensively performed in several autoimmune conditions and cumulatively suggest that some diseases, i.e. celiac disease and psoriasis, are highly genetically determined, while rheumatoid arthritis or systemic sclerosis have a limited role for genetics. These observations are necessary to interpret data gathered by genome-wide association studies of polymorphisms and DNA methylation in MZ twins. New high-throughput technological platforms are awaited to provide new insights into the mechanisms of disease discordance in twins beyond strong associations such as those with HLA alleles., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

It has been shown that many hereditary motor neuron diseases are caused by mutation of RNA processing enzymes. Survival of motor neuron 1 (SMN1) is well-known as a causative gene for spinal muscular atrophy (SMA) and mutations of glycyl- and tyrosyl-tRNA synthetases are identified as a cause of distal SMA and Charcot-Marie-Tooth disease. Why and how the dysfunction of these ubiquitously expressed genes involved in RNA processing can cause a specific neurological disorder is not well understood. Interestingly, SMN complex has been identified recently as a new target of autoantibodies in polymyositis (PM). Autoantibodies in systemic rheumatic diseases are clinically useful biomarkers associated with a particular diagnosis, subset of a disease, or certain clinical characteristics. Many autoantibodies produced in patients with polymyositis/dermatomyositis (PM/DM) target RNA-protein complexes such as aminoacyl tRNA synthetases. It is interesting to note these same RNA-protein complexes recognized by autoantibodies in PM/DM are also responsible for genetic neuromuscular disease. Certain RNA-protein complexes are also targets of autoantibodies in paraneoplastic neurological disorders. Thus, there are several interesting associations between RNA-processing enzymes and neuromuscular disorders. Although pathogenetic roles of autoantibodies to intracellular antigens are generally considered unlikely, understanding the mechanisms of antigen selection in a particular disease and specific neurological symptoms caused by disruption of ubiquitous RNA-processing enzyme may help identify a common path in genetic neuromuscular disorders and autoimmunity in inflammatory myopathies.

The purpose of this study was to evaluate the efficacy and safety of the Moderna-1273 mRNA vaccine for SARS-CoV-2 in patients with immune-mediated diseases under different treatments. Anti-trimeric spike protein antibodies were tested in 287 patients with rheumatic or autoimmune diseases (10% receiving mycophenolate mofetil, 15% low-dose glucocorticoids, 21% methotrexate, and 58% biologic/targeted synthetic drugs) at baseline and in 219 (76%) 4 weeks after the second Moderna-1273 mRNA vaccine dose. Family members or caretakers were enrolled as the controls. The neutralizing serum activity against SARS-CoV-2-G614, alpha, and beta variants in vitro and the cytotoxic T cell response to SARS-CoV-2 peptides were determined in a subgroup of patients and controls. Anti-SARS-CoV-2 antibody development, i.e., seroconversion, was observed in 69% of the mycophenolate-treated patients compared to 100% of both the patients taking other treatments and the controls (p < 0.0001). A dose-dependent impairment of the humoral response was observed in the mycophenolate-treated patients. A daily dose of >1 g at vaccination was a significant risk factor for non-seroconversion (ROC AUC 0.89, 95% CI 0.80–98, p < 0.0001). Moreover, in the seroconverted patients, a daily dose of >1 g of mycophenolate was associated with significantly lower anti-SARS-CoV-2 antibody titers, showing slightly reduced neutralizing serum activity but a comparable cytotoxic response compared to other immunosuppressants. In non-seroconverted patients treated with mycophenolate at a daily dose of >1 g, the cytotoxic activity elicited by viral peptides was also impaired. Mycophenolate treatment affects the Moderna-1273 mRNA vaccine immunogenicity in a dose-dependent manner, independent of rheumatological disease. [ABSTRACT FROM AUTHOR]

Introduction: Antimitochondrial antibodies (AMAs) are the hallmark of primary biliary cholangitis (PBC) but can be identified also in patients with connective tissue disease, namely, systemic sclerosis (SSc). Protein immunoprecipitation (IP) and IP-Western blot (WB) can be used to confirm AMA positivity directed at the pyruvate dehydrogenase complex (PDC) subunits E1α, E1β, E2/E3, and E3BP in patients showing a cytoplasmic reticular pattern at indirect immunofluorescence when performed in a screening setting before the onset of overt cholestasis in rheumatic patients. Patients and Methods: We studied sera from 285 patients affected by connective tissue disease [SSc, n = 144; dermato/polymyositis (DM/PM), n = 56; and undifferentiated connective tissue disease (UCTD), n = 85] by indirect immunofluorescence (IIF), protein-IP, and IP-WB to identify specific PDC subunits recognized by AMA. Results: Twenty percent (57/285) of sera from patients with connective tissue disease had a cytoplasmic reticular pattern at IIF, and in 77% (44/57, including 20 SSc, 12 PM/DM, and 12 UCTD) of these, we detected different titers of autoantibodies against the PDC subunits, specifically against PDC-E2. Among these sera, 4 (9%) tested positive for anti-E1α, 15 (34%) for anti-E1β, and 16 (36%) for anti-E3BP. Four of the 20 AMA-positive SSc cases (20%) had been already diagnosed with PBC, and all were positive for autoantibodies against the subunits PDC-E2, E3, and E3BP. Conclusions: Using IIF and IP, we confirm that autoantibodies against the PDC components are detected in rheumatic patients with PBC or without liver dysfunction. In view of the strong predictive value of AMA for PBC, a strict follow-up of these latter patients is warranted for an early diagnosis of the disease. [ABSTRACT FROM AUTHOR]

In the article, the authors present a case of a 27-year-old female with spondyloarthritis concomitantly with SARS-CoV-2 infection to discuss psoriatic arthritis triggered by said infection. In the case, the patient developed acute arthritis of the left ankle, dysgeusia and anosmia. Also cited are the subgroups of arthritis possibly linked to viral infections like reactive arthritis, viral arthritis and chronic arthritis.

The sequencing of the human genome is now well recognized as the starting point of personalized medicine. Nonetheless, everyone is unique and can develop different phenotypes of the same disease, despite identical genotypes, as well illustrated by discordant monozygotic twins. To recognize these differences, one of the easiest and most familiar examples of biomarkers capable of identifying and predicting the outcome of patients is represented by serum autoantibodies. In this review, we will describe the concept of personalized medicine and discuss the predictive, prognostic and preventive role of antinuclear antibodies (ANA), anti-citrullinated peptide antibodies (ACPA), rare autoantibodies and anti-drug antibodies (ADA), to evaluate how these can help to identify different disease immune phenotypes and to choose the best option for treating and monitoring rheumatic patients in everyday practice. The importance of ANA resides in the prediction of clinical manifestations in systemic sclerosis and systemic lupus erythematosus and their association with malignancies. ACPA have a predictive role in rheumatoid arthritis, they are associated with the development of a more aggressive disease, extra-articular manifestations and premature mortality in RA patients; moreover, they are capable of predicting therapeutic response. Rare autoantibodies are associated with different disease manifestations and also with a greater incidence of cancer. The determination of ADA levels may be useful in patients where the clinical efficacy of TNF-α inhibitor has dropped, for the assessment of a right management. The resulting scenario supports serum autoantibodies as the cornerstone of personalized medicine in autoimmune diseases. [ABSTRACT FROM AUTHOR]

The role of microRNAs (miRNAs) in the regulation of many physiological and pathological processes has been intensely studied in recent years. Some miRNAs, such as miR-146a and miR-182, play a dominant role in the regulation of the innate and adaptive immune responses, respectively. Many miRNAs are reportedly deregulated in autoimmune diseases, but miR-146a in particular seems to be consistently altered. The overexpression or underexpression of miRNAs can influence specific targets and pathways, leading to autoimmune disease phenotypes, and this is supported also by some in vivo studies. Targeting miRNAs could represent a valid future therapeutic option for autoimmune diseases. [ABSTRACT FROM AUTHOR]

The complement (C') cascade is an important part of the innate immunity. It acts through three major pathways: classical (CP), alternative (AP) and mannose-binding-lectin (MP). C' reduction is a key feature in systemic lupus erythematosus (SLE), for its pathogenesis and for disease relapse. The aims of our study are to correlate C' variations with disease activity and verify the presence of C' deficiencies. We tested for three C' pathways 52 sera from 20 patients affected by SLE. A significant correlation between the ECLAM score and the degree of activation of the CP (Mann-Whitney; P= 0.001) was recorded, while the correlation with anti-dsDNA antibodies did not reach statistical significance (Mann-Whitney; P > 0.05). In conclusion, the ELISA assay can be considered well suited for testing SLE samples. We detected a significant link between the phases of lupus activity and the reduction of the CP. [ABSTRACT FROM AUTHOR]