Autoimmune Connective Tissue Disease Research Articles

The role and mechanism of CRISPLD2 in skin fibrosis of systemic sclerosis.

Systemic sclerosis (SSc) is an autoimmune connective tissue disease involving multiple organs. The most common clinical symptom of SSc is progressive fibrosis of the skin, and the pathologically manifestations of skin were activation and proliferation of fibroblasts and continuous proliferation of extracellular matrix. Transforming growth factor β (TGFβ) can promote the proliferation and activation of fibroblasts, causing excessive deposition of collagen and structural proteins. Therefore, exploring the specific mechanism of TGFβ-related pathway on fibrosis is of great significance for improving skin fibrosis in SSc. Genes related to TGFβ pathway were screened through bioinformatics analysis, and SSc phenotypes were verified in vivo and vitro. The relevant molecular mechanisms were preliminarily discussed in combination with transcriptome sequencing. Human cysteine-rich secreted protein LCCL domain protein 2 (CRISPLD2) was found increased reactivity in TGFβ induced fibroblasts, and the expression of ACTA2 (ɑ-SMA) decreased significantly in TGFβ-mediated fibroblasts with up-regulation of CRISPLD2. CRISPLD2 was found increased reactivity in TGFβ induced fibroblasts, and we further confirmed that CRISPLD2 can participate in TGFβ induced fibroblast fibrosis from multiple perspectives and levels in negative feedback regulation, and investigated the mechanism of CRISPLD2 in fibrosis.

SARS-CoV-2 induced vitamin D deficiency and psychological stress: a manifestation of autoimmune disease onset.

The global SARS-CoV-2 pandemic significantly altered lifestyles, access to healthcare, and social interactions, introducing unprecedented physical and psychological stress all over the world. This study explores the relationship between psychological stress, vitamin D (Vit-D) levels, and autoimmune connective tissue diseases, including systemic lupus erythematosus, systemic sclerosis, polymyositis, dermatomyositis, and rheumatoid arthritis. The analysis was based on over one million patient data points derived from anti-nuclear antibody (ANA) testing conducted both before and during the COVID-19 pandemic 2017-2021. In a subset of patients, longitudinal data were collected bi-yearly to yearly over 5-8 years using the same three-month criteria. The dataset was analyzed using GraphPad Prism9 using paired t-tests or ordinary one-way ANOVA with a significance threshold of p < 0.05 to ensure robust correlations between the variables. Data indicated that Vit-D levels peaked between 2017 and 2019 before declining, while ANA data demonstrated a rise in autoimmune connective tissue disease cases during the pandemic, reaching a peak in 2021. A clear correlation was observed, with autoimmune disease incidence increasing as Vit-D levels decreased. In-depth case analysis revealed that declining Vit-D levels preceded higher ANA titers and increased autoimmune disease severity, whereas improvements in Vit-D levels were associated with reduced ANA titers and less severe disease manifestations. The findings suggest that maintaining mental health and ensuring adequate Vit-D supplementation could be essential strategies for mitigating autoimmune disease risks and maintaining immune stability, particularly in pandemic scenarios. Clinically, these results underscore the need for early interventions targeting both psychological well-being and Vit-D levels to reduce the burden of autoimmune diseases.

B-073 Analytical Performance of a Novel, Fully Automated Multiplexed Microarray Immunoassay Prototype for the Simultaneous Detection of Fifteen Autoantibodies Associated with Connective Tissue Diseases

Abstract Background There is currently a limited offer of automated multi-analyte tests for autoantibody testing in autoimmune connective tissue diseases (CTD). We assessed the analytical performance of a novel, single-use, multiplexed microarray immunoassay prototype (MosaiQ AiPlex CTDplus), used with the fully automated MosaiQ® system, for the simultaneous detection of fifteen autoantibodies associated with CTD, compared with selected CE-marked devices. Methods Banked human serum samples, characterized as reactive to ≥1 autoantibody or non-reactive were included. Reactive samples were characterized with FIDISTM Connective Profile (Theradiag) for CENP B, Jo-1, Ribosomal P, Scl-70, Sm, Sm/RNP, SS-A 60, TRIM21 (SS-A 52), SS-B and U1RNP; EliA CCP (Phadia) for CCP2, QUANTA Lite® Chromatin (Werfen) for Chromatin, QUANTA Flash® DFS70* (Werfen) for DFS70, Anti-dsDNA-IgG-ELISA (DRG) for dsDNA, and Immunodot (Euroimmun) for RNA polymerase III (RNAP III). For CCP2, only reactive samples were included. For the remaining analytes, non-reactive samples were characterized using immunofluorescence (ANA-Ro IgG FLUORESCENT HEp-2000®; Immuno Concepts, Germany) and ANAscreen ELISA (ORGENTEC-Diagnostika-GmbH, Germany). Each individual non-reactive sample was tested with the investigational device once; reactive samples were tested in duplicates. Positive percentage agreement (PPA) and negative percentage agreement (NPA) for individual analytes were calculated. For CCP2 only PPA is presented as no negative samples were included. Results Compared with relevant devices, the investigational prototype showed PPA ranging from 75% for chromatin to 99% for SS-A 60 and TRIM21. NPA ranged from 95% for chromatin, RNAP III, Scl-70 and Sm to 100% for DFS70, SS-A 60 and TRIM21. Performance details are shown in the Table. Conclusions The investigational prototype demonstrated substantial agreement with the compared CE-marked devices. Further studies will allow for expanded performance assessment of the investigational device. This fully-automated multiplexed platform has the potential to contribute to optimizing CTD evaluation by simplifying complex testing pathways and analyzing large number of samples per day.

Determination of antinuclear antibodies: role in modern differential diagnosis of connective tissue autoimmune diseases

There is an increase in autoimmune rheumatic diseases among all age population groups globally. Diagnosis is often difficult, because the early stages of the diseases usually do not have specific symptoms. Often, clinical manifestations of autoimmune diseases and non-autoimmune pathologies have similar symptoms. Therefore, the differential diagnosis could be very difficult. Most often, the determination of antinuclear autoantibodies is used for laboratory diagnosis of connective tissue systemic diseases. Autoantibodies can be detected in patients long time before the appearance of symptoms. The correct diagnosis is very important because the therapy of various nosologies can be different. It is especially significant with the invention of targeted therapy. Further analysis of the diagnostic value of autoantibody determination is very important. This article presents examination and follow-up data of three children. The analysis of medical documentation was carried out. The role of determining autoantibodies in the differential diagnosis of autoimmune connective tissue diseases was analyzed. In the first patient with Sjögren’s syndrome, the clinical picture of the underlying disease developed at least 5 years after the detection of high levels anti-SS-A, SS-B and Ro-52 antibodies (immunoblotting) and the speckled pattern (indirect immunofluorescence assay). In the second patient, antibodies against centromeres (specific markers of systemic scleroderma) appeared at least 2 years before clinical symptoms. In the third patient, the specific markers of systemic scleroderma have been detected for 5 years. There were antibodies against centromeres (immunoblotting), high titer and the centromere pattern (indirect immunofluorescence assay). However, the patient has not developed any clinical symptoms of this disease during all time of observation. Thus, the analysis of the presented clinical cases shows that autoantibodies can be detected in patients long time before the onset of clinical manifestations of a specific autoimmune disease. In all three cases, the first immunological examination has been carried out in the background of the disease symptoms, but they were atypical. Identification of specific autoantibodies, is very important for differential diagnosis. In the absence of clinical symptoms, the presence of autoantibodies, is the reason for dynamic observation of the patients.

Overlap syndrome: Juvenile dermatomyositis with systemic lupus erythematosus and lupus hepatitis in a child: An uncommon presentation

Autoimmune connective tissue disease in children carries a unique management challenge to the treating physician due to the potential years of disease burden and resultant complications. Early diagnosis and treatment positively impact disease course. Overlap syndrome in children is a rare entity. We report a case of juvenile dermatomyositis with systemic lupus erythematosus who on follow-up developed lupus hepatitis. Lupus hepatitis in children with overlap syndrome is not a well-known entity and there is paucity of literature describing this association.

Antinuclear Antibodies in Systemic Lupus Erythematous – Their Complex Role and Clinical Significance in Diagnosis

Antinuclear antibodies (ANA) are a wide group of proteins directed against autologous cellular components, primarily nucleic acids and histones. Their levels are assessed using immunofluorescence on Hep-2 cells or a solid-phase ANA screening immunoassay to subsequently obtain titer value with positive cut-point of ≥1:80. Studies show that ANA can be found in 13% of general population, but typically they are associated with autoimmune conditions and inflammatory connective tissue diseases for example: systemic lupus erythematosus (SLE), sjögren's syndrome, rheumatoid arthritis, mixed connective tissue disease, juvenile idiopathic arthritis, systemic sclerosis, inflammatory myopathies. ANA detection is especially important for SLE, where 2 antibody types - anti-Sm and anti-dsDNA - serve as an entry diagnostic criterion. With increasing patient screening for those antibodies, it is important to determine that alone, positive ANA assays cannot confirm nor deny any disease and to classify their presence as a marker of a disease it is required to satisfy additional additive criteria approved in 2019 by European League Against Rheumatism/American College of Rheumatology. SLE diagnosis can be made when patient collects 10 points from clinical or immunologic domains described by EULAR/ACR, which makes SLE diagnosis challenging and therefore, describing the guidelines is vital to remain cautious about overestimation of the position positive ANA values hold in clinical practice.In conclusion the positive ANA test may be a basis for diagnosis, when additional symptoms occur, but alone does not hold any diagnostic significance and may lead to unnecessary stress for patient.

The Relative Timing, Outcomes, and Economic Impact of Anti-Nuclear Antibody (ANA) and Extractable Nuclear Antigen (ENA) Laboratory Ordering.

Objective: To determine the rates of simultaneous antinuclear antibodies (ANA) screening and extractable nuclear antigen (ENA) testing that do not follow recommendations.Design, Setting, and Participants: Retrospective cohort study of adult patients (≥18 years) with a HEp-2 ANA or ENA ordered in the Marshfield Clinic Health System.Main Outcome(s) and Measure(s): Counts of patients having simultaneous ANA and ENA laboratory testing or ENA testing without ANA screening. Relevant ENA positivity in ANA negative patients. Secondary measures included relative timing of ANA and ENA ordering, potential cost savings of unnecessary testing, and provider ordering characteristics including specialty and provider type.Results: Of 58,627 cohort patients, 39,155 (66.8%) were women, and the mean (SD) age at first laboratory testing was 48.7 (19.0) years. The negative ANA with positive ENA rate was 2%. Further stratification identified only 23 diagnosed autoimmune connective tissue diseases (AI-CTDs) in this 2%, with a resulting negative ANA with relevant positive ENA rate of 0.37%. Simultaneous ANA and ENA testing occurred in 8.3% of patients, and an ENA only was ordered in 24.2% of patients. The simultaneous or non-sequential ordering of ANA and ENA testing resulted in significant health care costs of $2,293,251.80 over 20,112 unique patients.Conclusions and Relevance: A significant percentage of providers do not follow recommendations to sequentially order ANA and ENA testing on patients with suspected AI-CTDs. Significant saving in health care spending without failure to diagnose AI-CTDs can be achieved if ANA testing is performed first, followed by ENA testing when suspecting AI-CTDs in patients.

54767 Involvement of Calcinosis Cutis in Autoimmune Connective Tissue Diseases

54767 Involvement of Calcinosis Cutis in Autoimmune Connective Tissue Diseases

53877 Diversity in Clinical Trials for Autoimmune Connective Tissue Disease

53877 Diversity in Clinical Trials for Autoimmune Connective Tissue Disease

Identification and Quantification of Precursory Changes of Rheumatoid Vasculitis in the Dorsalis Pedis Artery

ObjectiveRheumatoid arthritis (RA) is a systemic connective tissue autoimmune disease that can infiltrate arterial walls. The delay in diagnosis and treatment of rheumatoid vasculitis (RV) in patients with RA may lead to irreversible damage to the arterial walls of small-to-medium vessels, which has serious and devastating consequences, most notably lung and cardiac damage. In this work an ultrasound image-based biomarker was developed to detect precursory changes in RV. MethodsThe ground truth was initiated from a medical diagnosis of RA, with arterial wall thickening of the proximal dorsalis pedis artery (DPA) indicating precursory changes of RV identified with ultrasound scanning. Ultrasound images of the DPA from 49 healthy subjects in the control group and 46 patients in the RA group were obtained. In total, 187 texture features were extracted from the images, followed by principal component analysis and linear discriminant analysis. ResultsThe proposed biomarker detected a significant difference between the two groups (p = 5.74 × 10-18) with an area under the receiver operating characteristic curve of 0.85. Ten major textural features contributing most heavily to the biomarker were identified, with these textures being consistent with clinical observations of RV identified in previous studies. Interscan reproducibility was assessed by computing the biomarker twice based on repeated scans of each ankle. High interscan reproducibility was demonstrated by a strong and significant Pearson's coefficient (r = 0.85, p < 0.01) between the two repeated measurements of the proposed biomarker. ConclusionThe proposed biomarker can discriminate image textural differences seen in images acquired from RA patients, demonstrating precursory changes in RV compared with healthy controls. The major discriminative features identified in this study may facilitate the early identification and treatment of RV.

Audiovestibular Involvement in Patients With Systemic Sclerosis.

Audiovestibular dysfunction has been reported in many autoimmune connective tissue diseases, including systemic sclerosis (SSc). To assess the prevalence and features of audiological and vestibular disturbances in SSc patients and evaluate their relationship with disease duration, clinical features, nailfold videocapillaroscopy pattern, and immunologic profiles. A matched case-control study was conducted in a rheumatology clinic of a second-level hospital over 24 months. All patients underwent a detailed ear, nose, and throat examination, as well as audiometric and vestibular assessments, including pure tone audiometry, speech audiometry, immittance tests, and the Video Head Impulse Test. Thirty-five SSc patients and 24 healthy controls were included in the study. In the SSc group, subjective hearing loss was reported by 17.1% of patients, vertigo by 14.3%, tinnitus by 11.4%, and dizziness by 5.7%. Sensorineural hearing loss was identified in 42.9% of SSc patients, significantly higher than in the control group (p = 0.013). There was no correlation between audiological manifestations and clinical symptoms, organ involvement, immunologic characteristics, and treatment. Vestibular dysfunction was detected in 60% of SSc patients, significantly higher than the control group (p = 0.05). A significant correlation was found between abnormal Video Head Impulse Test and the presence of anti-RNA polymerase III and anti-Th/To antibodies (p = 0.05 and p = 0.034, respectively). Our study revealed an increased prevalence of sensorineural hearing loss and vestibulopathy in SSc patients.

Macrophage colony-stimulating factor receptor/CD115+ non-classical monocytes are expanded in systemic lupus erythematosus and associated with lupus nephritis

Objective In systemic lupus erythematosus (SLE), the non-classical monocyte compartment is expanded, but its phenotype and association with clinical disease manifestations have not been explored. Method Monocyte subsets from 39 SLE patients, 32 healthy age-matched controls, and 16 patients from a disease control (autoimmune connective tissue disease other than SLE) were determined based on CD14 and CD16 surface expression. Cell surface expression of the receptors for macrophage colony-stimulating factor (M-CSF) (CD115) and granulocyte–macrophage colony-stimulating factor (GM-CSF) (CD116), as well as 6-Sulpho LacNAc (slan), were analysed by flow cytometry. The association of monocyte populations with disease manifestations, disease activity markers, and current medication of each patient was analysed by chart review. Results Non-classical monocytes displayed a cell-type specific signature of high M-CSF receptor CD115 and low GM-CSF receptor CD116 expression that separated them from the other two monocyte subsets. In healthy individuals, the M-CSF receptor on non-classical monocytes was an age-dependent surface marker, with lower expression in young adults. However, SLE monocytes were characterized by a marked expansion of M-CSF receptor/CD115+ non-classical monocytes in patients of all ages. The expanded population of M-CSF receptor/CD115+ non-classical monocytes was associated with lupus nephritis but not with disease activity, and coexpressed slan. Conclusion The non-classical monocyte subset in SLE is characterized by an expansion of M-CSF receptor/CD115+ cells that are associated with lupus nephritis and coexpress slan.

Characterizing the Links Between Systemic Sclerosis and Breast Cancer.

Systemic sclerosis (SSc) is a complex, autoimmune connective tissue disease that affects multiple organs in the body, culminating in a variance of severity and a reduced quality of life. Breast cancer (BC) also affects patients with SSc, and these two conditions affect a similar demographic. With this systematic review, we aim to characterize the links between SSc and BC. Characterizing possible links between SSc and breast malignancies is important for advancing the understanding of SSc management and comorbidities. In this systematic meta-analysis, a comprehensive literature search was conducted in PubMed using relevant keywords and MeSH terms. The inclusion criteria included an English-language retrospective analysis that characterized patients with SSc with or without BC. Two independent reviewers assessed the study's eligibility based on predetermined criteria. Data extraction included patient antibody measurements, demographics (age and gender), family history, social behaviors (alcohol use and smoking history), concurrent condition treatments, and adverse effects following treatment. Thirteen articles were identified in the literature with relevant data on SSc and BC patients. Studies encompassed research about SSc patients with or without BC and relevant risk factors being measured. SSc was found to have a link to antibodies widely associated with cancer. Adverse treatment outcomes and concurrent conditions of BC were found when patients had a family history of SSc, BC, or an alcohol or smoking history. Our results suggest that the presence of antinuclear antibodies, anti-centromere antibodies, or anti-topoisomerase antibodies in SSc patients is correlated with BC. Out of the three antibodies, ATA seemed to be found more commonly in patients with SSc and malignancy across the studies. This systematic review discusses the link between SSc and BC through patients with relevant clinical markers, medical histories, and treatments. However, further research is necessary to advance the linkage between SSc and BC and determine whether management of one condition may prevent or alleviate the other.

Earlier vs. later time period of COVID-19 infection and emergent autoimmune signs, symptoms, and serologies

ObjectiveAutoantibodies and autoimmune diseases after SARS-CoV-2 infection are widely reported. Given evolving variants, milder infections, and increasing population vaccination, we hypothesized that SARS-CoV-2 infection earlier in the pandemic would be associated with more autoimmune connective tissue disease (CTD) symptoms and immunologic abnormalities. MethodsPatients ≥18 years old with COVID-19 3/1/2020-8/15/2022 completed the CTD Screening Questionnaire and were tested for 27 autoimmune serologies, SARS-CoV-2 serologies, cell-bound complement activation products (CB-CAPs), and T and B lymphocyte immunophenotypes by flow cytometry. We assessed relationships between symptoms, serologies, and immunophenotypes in earlier (3/1/2020-1/31/2021) vs. later (2/1/2021-8/15/2022) periods, with different predominating SARS-CoV-2 viruses. Results57 subjects had earlier and 23 had later pandemic COVID-19. 35 % of earlier vs. 17 % of later pandemic patients had CTD symptoms (p 0.18). More patients were antinuclear antibody (ANA) positive (44 % vs. 13 %, p 0.01) and had lupus anticoagulant (11 % vs. 4 %, p 0.67). After adjustment for age, race, and sex, earlier (vs. later) COVID-19 was associated with increased ANA positivity (OR 4.60, 95%CI 1.17, 18.15). No subjects had positive CB-CAPs. T and B cell immunophenotypes and SARS-CoV-2 serologies did not differ by group. In heatmap analyses, higher autoantibody variety was seen among those with infection in the early pandemic. ConclusionIn this sample, having COVID-19 infection in the earlier (pre-2/1/2021) vs. later pandemic was associated with more CTD symptoms, ANA positivity, and autoantibody reactivities. Earlier SARS-CoV-2 variants circulating in a less vaccinated population with less natural immunity may have been more immunogenic.

Placental Pathologic Features and Perinatal Outcomes in Pregnant Woman With Autoimmune Connective Tissue Disease.

We aimed to investigate the association between perinatal outcomes and placental pathological features in pregnant women with ACTD, including systemic lupus erythematosus (SLE), antiphospholipid antibody syndrome (APS), and undifferentiated connective tissue disease (UCTD). Placental tissue from SLE (n=44), APS (n=45), and UCTD (n=45) were included, and contemporaneous deliveries of placenta were served as a control group (n=46) between September 2015 and March 2021. The placental histopathology was evaluated using the Manual of Human Placental Pathology and classified according to the Amsterdam consensus framework. SLE pregnant women have a higher rate of cesarean section (61.40%), premature birth (24.56%), and SGA (26.32%) when compared to control group (p=0.008, p=0.005, and p=0.000, respectively). The rate of vascular malperfusion, inflammatory-immune lesions, and other placental lesions in the SLE group was 47.73%, 56.82%, and 63.64%, which were higher than the control group (p=0.000, p=0.000, and p=0.006, respectively). In the meantime, the incidence of inflammatory-immune lesions in the APS group (42.22%, p=0.004) and vascular malperfusion in the UCTD group (37.78%, p=0.007) were increased when compared to the control group. SLE appeared to confer increased risk for a wide range of adverse perinatal outcomes. We determined elevated placental histopathology risk for most women with ACTD, including vascular maldevelopment, vascular malperfusion, and inflammatory-immune lesions.

Long-term risk of autoimmune diseases after mRNA-based SARS-CoV2 vaccination in a Korean, nationwide, population-based cohort study

The long-term association between mRNA-based coronavirus disease 2019 (COVID-19) vaccination and the development of autoimmune connective tissue diseases (AI-CTDs) remains unclear. In this nationwide, population-based cohort study involving 9,258,803 individuals, we aim to determine whether the incidence of AI-CTDs is associated with mRNA vaccination. The study spans over 1 year of observation and further analyses the risk of AI-CTDs by stratifying demographics and vaccination profiles and treating booster vaccination as time-varying covariate. We report that the risk of developing most AI-CTDs did not increase following mRNA vaccination, except for systemic lupus erythematosus with a 1.16-fold risk in vaccinated individuals relative to controls. Comparable results were reported in the stratified analyses for age, sex, mRNA vaccine type, and prior history of non-mRNA vaccination. However, a booster vaccination was associated with an increased risk of some AI-CTDs including alopecia areata, psoriasis, and rheumatoid arthritis. Overall, we conclude that mRNA-based vaccinations are not associated with an increased risk of most AI-CTDs, although further research is needed regarding its potential association with certain conditions.

Vitamin D and Muscle Status in Inflammatory and Autoimmune Rheumatic Diseases: An Update.

Background and Objectives: Vitamin D is a secosteroid hormone essential for calcium homeostasis and skeletal health, but established evidence highlights its significant roles also in muscle health and in the modulation of immune response. This review aims to explore the impact of impaired vitamin D status on outcomes of muscle function and involvement in inflammatory and autoimmune rheumatic diseases damaging the skeletal muscle efficiency both with direct immune-mediated mechanisms and indirect processes such as sarcopenia. Methods: A comprehensive literature search was conducted on PubMed and Medline using Medical Subject Headings (MeSH) terms: "vitamin D, muscle, rheumatic diseases." Additionally, conference abstracts from The European Alliance of Associations for Rheumatology (EULAR) and the American College of Rheumatology (ACR) (2020-2023) were reviewed, and reference lists of included papers were scanned. The review emphasizes the evidence published in the last five years, while also incorporating significant studies from earlier years, structured by the extent of evidence linking vitamin D to muscle health in the most commonly inflammatory and autoimmune rheumatic diseases encountered in clinical practice. Results: Observational studies indicate a high prevalence of vitamin D serum deficiency (mean serum concentrations < 10 ng/mL) or insufficiency (<30 ng/mL) in patients with idiopathic inflammatory myopathies (IIMs) and polymyalgia rheumatica, as well as other autoimmune connective tissue diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). Of note, vitamin D insufficiency may be associated with reduced muscle strength (2 studies on RA, 2 in SLE and 1 in SSc), increased pain (1 study on SLE), fatigue (2 studies on SLE), and higher disease activity (3 studies on IIMs and 1 on SLE) although there is much heterogeneity in the quality of evidence and different associations for the different investigated diseases. Therefore, linked to the multilevel biological intervention exerted by vitamin D, several translational and clinical studies suggest that active metabolites of this secosteroid hormone, play a role both in reducing inflammation, but also in enhancing muscle regeneration, intra-cellular metabolism and mitochondrial function, although interventional studies are limited. Conclusions: Altered serum vitamin D status is commonly observed in inflammatory and autoimmune rheumatic diseases and seems to be associated with adverse muscle health outcomes. While maintaining adequate serum vitamin D concentrations may confer muscle-protective effects, further research is needed to confirm these findings and establish optimal supplementation strategies to obtain a safe and efficient serum threshold.

The Novel Cytokine Interleukin-41/Meteorin-like Is Reduced in Diffuse Systemic Sclerosis.

Systemic sclerosis (SSc) is an autoimmune connective tissue disease with a triad of features that include vascular abnormalities, inflammation and skin and lung fibrosis. At the core of the disease is the activation of myofibroblasts from quiescent fibroblasts and this can be modified by various cytokines. IL-41 is a recently described cytokine that was initially characterised as an adipokine as it was highly expressed in adipocytes and adipose tissue. However, it has recently been identified as being widely expressed and has immunomodulatory functions. This study examined the circulating levels of IL-41 and its expression in skin biopsies. We demonstrated significantly reduced levels of IL-41 in diffuse SSc that was also mirrored in the skin of SSc patients. AMPK has been proposed as a downstream target of IL-41, so we also measure mammalian target of rapamycin in skin and found that this is elevated in SSc patients. We speculate that IL-41 maybe an antifibrotic cytokine and its reduction may facilitate the activation of fibroblasts.

Treatment of calcinosis cutis associated with autoimmune connective tissue diseases.

Calcinosis cutis is a condition that is commonly associated with autoimmune connective tissue diseases. It is characterized by the deposition of insoluble calcium salts in the skin and subcutaneous tissue, which can cause pain, impair function, and have significant impacts on quality of life. Calcinosis cutis is difficult to manage because there is no generally accepted treatment: evidence supporting treatments is mostly comprised of case reports and case series, sometimes yielding mixed findings. Both pharmacologic and procedural interventions have been proposed to improve calcinosis cutis, and each may be suited to different clinical scenarios. This review summarizes current treatment options for calcinosis cutis, with discussion of recommendations based on patient-specific factors and disease severity.

Calcinosis Prevalence in Autoimmune Connective Tissue Diseases-A Retrospective Study.

Background/Objectives: Calcinosis cutis is the deposition of insoluble calcium salts, which may cause inflammation, ulceration, pain, and restricted joint mobility. It rarely develops in damaged tissues (dystrophic subtype), most frequently in autoimmune connective tissue diseases (CTDs), but there is very limited data on the prevalence. Also, therapy remains an unsolved issue. In this study, we aimed to collect data on the prevalence of calcinosis in CTD patients to highlight that it is a considerable problem. Methods: A retrospective study was conducted in our department to assess the epidemiology of dystrophic calcinosis in CTDs between January 2003 and January 2024. Results: A total of 839 CTD patients were identified, of whom 56 had calcinosis (6.67%). The mean age of the calcinosis patients at diagnosis of underlying CTD was 41.16 ± 19.47 years. The mean time interval from the onset of calcinosis was 5.96 ± 8.62 years. Systemic sclerosis was the most common CTD complicated by calcinosis (n = 22). Conclusions: Our results are comparable to those reported previously in the literature. Although calcinosis is rare in the overall population, it is a present and unsolved problem in CTD patients. Therefore, further studies are needed on the factors involved in the development and progression of calcinosis as well as its treatment.