Autoimmune Connective Tissue Disease Research Articles

Proteomic aptamer analysis reveals serum biomarkers associated with disease mechanisms and phenotypes of systemic sclerosis.

Systemic sclerosis (SSc) is an autoimmune connective tissue disease that affects multiple organs, leading to elevated morbidity and mortality with limited treatment options. The early detection of organ involvement is challenging as there is currently no serum marker available to predict the progression of SSc. The aptamer technology proteomic analysis holds the potential to correlate SSc manifestations with serum proteins up to femtomolar concentrations. This is a two-tier study of serum samples from women with SSc (including patients with interstitial lung disease - ILD - at high-resolution CT scan) and age-matched healthy controls (HC) that were first analyzed with aptamer-based proteomic analysis for over 1300 proteins. Proposed associated proteins were validated by ELISA first in an independent cohort of patients with SSc and HC, and selected proteins subject to further validation in two additional cohorts. The preliminary aptamer-based proteomic analysis identified 33 proteins with significantly different concentrations in SSc compared to HC sera and 9 associated with SSc-ILD, including proteins involved in extracellular matrix formation and cell-cell adhesion, angiogenesis, leukocyte recruitment, activation, and signaling. Further validations in independent cohorts ultimately confirmed the association of specific proteins with early SSc onset, specific organ involvement, and serum autoantibodies. Our multi-tier proteomic analysis identified serum proteins discriminating patients with SSc and HC or associated with different SSc subsets, disease duration, and manifestations, including ILD, skin involvement, esophageal disease, and autoantibodies.

Animal models in systemic sclerosis: an update.

Systemic sclerosis (SSc) is a multisystem autoimmune connective tissue disease characterized by early inflammation followed by excessive fibrosis in the skin and internal organs. Enhancing our comprehension of SSc pathogenesis is essential to develop effective therapeutic strategies. Animal models that mimic one or more aspects of SSc have been proven to be a valuable resource for investigating disease mechanisms. This review aims to provide an updated overview of the existing SSc animal models and the potentially relevant pathways to SSc pathogenesis. This review focuses on the most recently generated and investigated animal models, which delve into novel pathways beyond existing models or employ genetic technologies to gain a deeper understanding of SSc pathogenesis including activation of early type I interferon (IFN) signaling pathway, immune cell function and pulmonary artery hypertension (PAH). While no single animal model can fully replicate SSc, a combination of different models can offer valuable insights into the pathways involved in the onset and advancement of the SSc. These insights can prove animal models as a crutial preclinical tool for developing effective treatments for SSc.

Comparison of telerehabilitation methods for patients with systemic sclerosis in the COVID-19 Era: A randomized controlled study

Study DesignThis was a single-blinded randomized clinical trial. IntroductionSystemic sclerosis (SSc) is an autoimmune connective tissue disease that progresses with fibrosis. Patients with SSc need to be protected against epidemic diseases and provided for in terms of rehabilitation needs. Purpose of the StudyTo compare the effects of real-time telerehabilitation (RTT) and asynchronous telerehabilitation (AT) on individuals with SSc. MethodsForty-two participants with SSc with a mean age of 44.17 ± 11.05 years were included in the study. The patients were randomly divided into three groups, RTT (n = 16), AT (n = 16), and control (n = 16) groups. A structured rehabilitation program was performed in real-time (RTT group) and asynchronously (AT group) for 40 minutes per day, in three sessions per week for 8 weeks. The participants' finger and wrist joint range of motion (ROM), upper extremity functions, grip strength, superficial sense of touch, activities of daily living (ADL), and general health status were assessed at baseline and after treatment. ResultsAfter 8 weeks, there were improvements in finger ROM (effect size [ES] = 0.23 to 0.60), wrist ROM (ES = 0.45 to 0.83), upper extremity functions (ES = 0.61 to 1.00), and ADL parameters (ES = 0.74) in the RTT group (p < 0.05). Also, there were improvements in finger ROM (ES = 0.16 to 0.45) and hand functions (ES = 0.54 to 0.55) in the AT group (p < 0.05). The RTT and AT groups had better hand functions and finger ROM than the control group in (p < 0.05). In addition, the RTT group had better wrist ROM than the control group (p = 0.008). RTT was superior to AT only in lateral pinch strength (p = 0.025). DiscussionExperimental groups achieved a statistically significant change in ROM, upper extremity functions and ADL over time in concordance with prior investigations. Changes in grip strength, superficial sense of touch, and general health status scores differed from previous investigations and the between-group comparison was not statistically significant. ConclusionsBoth RTT and AT may be effective in individuals with SSc, and RTT has additional benefits.

Systemic Scleroderma: A Deep Dive into the Complexity of a Multi-System Autoimmune Connective Tissue Disease

Systemic scleroderma, a complex and rare autoimmune connective tissue disease, represents a significant clinical and scientific challenge due to its clinical heterogeneity, multisystem involvement, and potential for severe disability and complications. This article examines in depth the epidemiological, clinical, diagnostic and therapeutic aspects associated with this complex condition. Through a comprehensive review, it highlights the importance of a multidisciplinary medical approach to properly evaluate and manage the disease, from early detection to the implementation of specific therapeutic strategies targeting affected organs and systems. It also emphasizes the need for continued research to better understand the underlying pathogenic mechanisms and develop more effective therapies, with the goal of improving the outcomes and quality of life of patients affected by this complex autoimmune condition.

Hiding in Plain Sight: Human Gingival Fibroblasts as an Essential, Yet Overlooked, Tool in Regenerative Medicine.

Adult human gingival fibroblasts (HGFs), the most abundant cells in the oral cavity, are essential for maintaining oral homeostasis. Compared with other tissues, adult oral mucosal wounds heal regeneratively, without scarring. Relative to fibroblasts from other locations, HGFs are relatively refractory to myofibroblast differentiation, immunomodulatory, highly regenerative, readily obtained via minimally invasive procedures, easily and rapidly expanded in vitro, and highly responsive to growth factors and cytokines. Consequently, HGFs might be a superior, yet perhaps underappreciated, source of adult mesenchymal progenitor cells to use in tissue engineering and regeneration applications, including the treatment of fibrotic auto-immune connective tissue diseases such as scleroderma. Herein, we highlight in vitro and translational studies that have investigated the regenerative and differentiation potential of HGFs, with the objective of outlining current limitations and inspiring future research that could facilitate translating the regenerative potential of HGFs into the clinic.

ATRA ameliorates fibrosis by suppressing the pro-fibrotic molecule Fra2/AP-1 in systemic sclerosis.

Systemic sclerosis (SSc) is an autoimmune connective tissue disease that leads to irreversible fibrosis of the skin and the internal organs. The etiology of SSc is complex, its pathophysiology is poorly understood, and clinical therapeutic options are restricted. Thus, research into medications and targets for treating fibrosis is essential and urgent. Fos-related antigen 2 (Fra2) is a transcription factor that is a member of the activator protein-1 family. Fra2 transgenic mice were shown to have spontaneous fibrosis. All-trans retinoic acid (ATRA) is a vitamin A intermediate metabolite and ligand for the retinoic acid receptor (RAR), which possesses anti-inflammatory and anti-proliferative properties. Recent research has demonstrated that ATRA also has an anti-fibrotic effect. However, the exact mechanism is not fully understood. Interestingly, we identified potential binding sites for the transcription factor RARα to the promoter region of the FRA2 gene through JASPAR and PROMO databases. In this study, the pro-fibrotic effect of Fra2 in SSc is confirmed. SSc dermal fibroblasts and bleomycin-induced fibrotic tissues of SSc animals exhibit increased levels of Fra2. Inhibition of Fra2 expression in SSc dermal fibroblasts with Fra2 siRNA markedly decreased collagen I expression. ATRA reduced the expressions of Fra2, collagen I, and α-smooth muscle actin(α-SMA) in SSc dermal fibroblasts and bleomycin-induced fibrotic tissues of SSc mice. In addition, chromatin immunoprecipitation and dual-luciferase assays demonstrated that retinoic acid receptor RARα binds to the FRA2 promoter and modulates its transcriptional activity. ATRA decreases collagen I expression both in vivo and in vitro via the reduction of Fra2 expression. This work establishes the rationale for expanding the use of ATRA in the treatment of SSc and indicates that Fra2 can be used as an anti-fibrotic target.

Microvascular damage in autoimmune connective tissue diseases: a capillaroscopic analysis from 20 years of experience in a EULAR training and research referral centre for imaging

ObjectiveNailfold videocapillaroscopy (NVC) allows the detection of microvascular damage in autoimmune connective tissue diseases (CTDs). The prevalence of the morphological capillary findings was retrospectively evaluated in a wide cohort of...

Elevated interleukin-11 in systemic sclerosis and role in disease pathogenesis.

Systemic sclerosis (SSc) is an autoimmune connective tissue disease in which there is elevated inflammation, aberrant cytokine expression, and subsequent fibrosis. Interleukin-11 (IL-11) is a recently described profibrotic cytokine that can mediate fibrosis in the heart, lungs, and skin and is upregulated by transforming Growth Factor-β (TGF-β1). The objective of this study was to quantify the serum levels of IL-11 in early diffuse SSc patients. Also, if IL-11 could regulate the alarmin IL-33 in dermal fibroblasts was quantified. Early diffuse SSc patient sera was isolated and IL-11 was quantified by specific commercial ELISA compared to healthy control (n = 17). Healthy dermal fibroblasts were cultured in vitro and then serum starved and incubated with or without recombinant IL-11. At specific early and late time points the supernatant was quantified for the alarmin IL-33 by specific ELISA. In early diffuse SSc patients it was demonstrated that they have elevated IL-11 in their sera. In a subgroup of SSc patients with interstitial lung disease (ILD) this elevation was particularly pronounced compared to those devoid of fibrotic lung disease. In vitro incubation of healthy dermal fibroblasts led to a significant induction of IL-33 cytokine release into the cell media. IL-11 is a profibrotic cytokine that is elevated in early diffuse SSc and is particularly elevated in those with ILD. This suggests that IL-11 could be a possible biomarker of ILD in SSc. It was also found that IL-11 led to release of the cytokine alarmin IL-33 in fibroblasts at earlier time points but not late time points, suggesting early stimulation elicits an inflammatory response in the local microenvironment but prolonged stimulation leads to fibrosis.

Integrating the autoimmune connective tissue diseases for the medical student: A classification proposal based on pathogenesis and clinical phenotype

It is hard for medical students to recognize and understand the clinical presentation of systemic connective tissue diseases (SCTDs). In this study, we aimed to review the immune mechanisms of the main SCTDs and to propose a classification system focused on the student and based on each immune dysfunction’s clinical phenotype. The search involved the MEDLINE database and included the terms “systemic lupus erythematosus,” “antiphospholipid syndrome,” “inflammatory myopathies,” “rheumatoid arthritis,” “Sjögren’s syndrome” or “systemic sclerosis” and “pathogenesis,” and “immunology” or “mechanism of disease.” Systemic lupus erythematosus (SLE) is a prototypic immune-complex disease with a tendency toward vascular injury. Antiphospholipid syndrome (APS) is a diffuse immune-mediated thrombotic vasculopathy. In inflammatory myopathies (IMs), muscle inflammation leading to muscle weakness is the cardinal manifestation. Rheumatoid arthritis (RA) is a unique form of erosive and destructive polyarthritis. Sjögren’s syndrome (SS) causes sicca symptoms due to infiltration of the exocrine glands. Disseminated fibrosis in systemic sclerosis (SSc) is caused by vascular injury with excessive fibroblast activation. After the review, we created a focus group involving all the authors to group the diseases according to their pathogenesis and clinical phenotype. Our group agreed that SCTDs can be divided in 3 groups based on the preferential clinical presentation and immune dysfunction: 1) vasculopathic features (SLE and APS), 2) tissue inflammation (IMs, RA, and SS), and 3) tissue fibrosis (SSc). In synthesis, we suggest that clustering SCTDs in groups based on clinical phenotype and presumptive immune dysfunction instead of ordering autoantibodies randomly can help students understand the diseases.

Views of Exercise in People With Systemic Sclerosis: A Qualitative Study

ABSTRACT Background Systemic sclerosis (SSc) is a connective tissue autoimmune disease that results in significant reduction in physical function and quality of life. Exercise may offer health benefits in people with autoimmune disease, yet approximately 50% of people with SSc are physically inactive and experience a wide array of barriers that may impede their exercise engagement. Currently, there are no exercise recommendations or guidelines for this population. In this qualitative study, we explore and describe barriers and facilitators to exercise in adults with SSc, aiming to provide person-centerd exercise recommendations for people with SSc. Methods Adults with SSc were purposefully recruited to represent diversity in disease type, duration, and manifestations. Three online focus groups were conducted to explore barriers and facilitators to exercise in people with SSc, transcribed, and thematically analyzed. Results Twenty-three adults with SSc (mean age 59 ± 11 years, 91% female) participated. Four themes emerged: (a) disease-related and general barriers to exercise, (b) perceived change in personal exercise capacity postdiagnosis, (c) beneficial effects of exercise, and (d) preference for modified supervised exercise. Conclusion SSc imposes disease-related barriers that, combined with general barriers, impede exercise engagement. People with SSc understand that exercise is potentially beneficial. Key recommendations and advice to counter these barriers include (a) ensuring a comfortable temperature to exercise, (b) using modified equipment (e.g., adjustable weighted straps), (c) individually supervising and modifying exercise as required, and (d) keeping people with SSc accountable and motivated to exercise.

Acute Outcomes of Cardiac Operations in Patients With Autoimmune Disorders: A National Analysis.

Accelerated atherosclerosis, inflammation, and valve pathology are known complications of autoimmune connective tissue diseases (AID). However, outcomes of coronary artery bypass graft surgery (CABG) or valve operations among these patients remain underexamined. All adult hospitalizations for elective CABG or valve procedures were identified from the 2010-2019 Nationwide Readmissions Database. Autoimmune connective tissue disease was defined to include systemic lupus erythematosus (SLE), antiphospholipid syndrome (APLS), polymyalgia rheumatica (PMR), and other autoimmune AIDs. Entropy balancing was applied to generate balanced patient cohorts. Multivariable regression models were constructed to assess the independent associations between AID and outcomes of interest. Of ∼1 652 573 patients, 21 019 (1.3%) had AID (23.7% SLE, 17.2% APLS, 29.5% PMR, and 29.6% other). Autoimmune connective tissue disease patients were more frequently female (60.8 vs 33.1%, P < .001) and insured by Medicare (71.4 vs 62.2%, P < .001) and presented with a higher comorbidity index (5.2 ± 1.8 vs 4.1 ± 1.8, P < .001). Further, AID less frequently underwent isolated CABG (39.0 vs 52.3%) but more commonly isolated valve operations (41.9% vs 31.0%, P < .001), relative to non-AID. Following risk-adjustment, AID was not linked with increased odds of mortality or cardiac complications. However, AID was linked with a greater risk of thrombotic complications, blood transfusion, and non-elective readmission within 30days, as well as a +$900 decrement in hospitalization costs. Autoimmune connective tissue disease patients demonstrated acceptable outcomes following CABG and valve procedures. However, novel prophylactic care pathways should be developed and instituted to address greater thrombotic and blood transfusion risk. Further investigation is needed to identify factors contributing to greater non-elective readmissions among these patients.

Decreased Prevalence of Autoimmune Connective Tissue Diseases in Type 1 and Type 2 Diabetes

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Ultrasound Morphea Activity Scoring (US-MAS): Modified US-MAS.

Morphea, an autoimmune connective tissue disease that affects the skin, can be supported by color Doppler ultrasound in its diagnosis and assessment of activity. To date, there are no reliable laboratory parameters to track activity, and ultrasound presents a higher axial spatial resolution than magnetic resonance imaging and computed tomography, which is critical for studying the superficial layers. The quality of the ultrasonographic assessment of activity in morphea depends on the standardization and features of the acquisition of the anatomical data. We propose a detailed ultrasound morphea activity scoring called modified US-MAS (mUS-MAS) that could allow us to systematically register the cutaneous abnormalities in the corporal regions and their subregions. The selection of the scanning sites will depend on the corporal regions of involvement and their adjacent segments. Through systematic and sequential ultrasound data analysis, we propose that this scoring system can better support description and activity tracking accuracy.

CXCL4, a chemokine upregulated in systemic sclerosis patients, abrogates TLR9 signaling and central tolerance in B cells

Abstract Background: Systemic sclerosis (SSc) is an autoimmune connective tissue disease, characterized by defective central B cell tolerance. Deficiency of MYD88, which mediates the function of TLRs, results in a failure to silence autoreactive B cells. CXCL4, a chemokine found elevated in the sera of SSc patients, potentiates IFN-α secretion from TLR9-induced plasmacytoid dendritic cells. The objective is to investigate whether CXCL4 regulates TLR9 signaling and central tolerance in B cells. Methods: B cells from SSc patients or healthy donors were cultured with TLR9 ligand (TLR9-L) alone or with CXCL4. Cytokines gene expression and secretion were analyzed. Delivery of TLR9-L was analyzed by Amnis and confocal microscopy. NOD-scid-common gamma chain (γc) knockout immunodeficient mice were engrafted with CD34 +human fetal hematopoietic stem cells transduced with lentivirus expressing human CXCL4. New emigrant/transitional B cells were sorted. Immunoglobulins chains of these cells were cloned and transfected in fibroblasts. Polyreactivity of the antibodies released by the fibroblasts were assessed. Results: Defective TLR9 signaling was observed in B cells of SSc patients. CXCL4 abrogated TLR9 response in human B cells. TLR9-L when given to B cells alone, was localized in the lysosomes and LAMP-2 +compartments while CXCL4 prevented the delivery of TLR9-L to these vesicles. CXCL4 in vivoexpression led to defective TLR9 responses and increased number of polyreactive B cells. Conclusions: Our data provide evidence for a novel mechanism by which CXCL4 impairs central B cell tolerance by altering the intracellular trafficking of TLR9 ligands, hence inhibiting TLR9 response which is required for the removal of developing autoreactive B cells.

Factor XIII and Endothelial Dysfunction in Patients with Systemic Sclerosis.

Systemic sclerosis (SSc, scleroderma) is a severe autoimmune connective tissue disease which affects the skin and internal organs. There has been evidence that coagulation factor XIII (FXIII) has a positive impact on clinical results in patients with SSc. In a single-center cohort study, we investigated the relationship between coagulation FXIII, endothelial dysfunction, and skin infection in SSc. Fifty-six patients could be included and were divided into two groups (with and without scleroderma). Markers of inflammation, coagulation, and endothelial dysfunction like C-reactive protein, leucocytes, fibrinogen, FVIII, VWF-Ag (von Willebrand factor antigen), D-dimers, and vascular endothelial growth factor were analyzed as well as MRSS (modified Rodnan skin scores) data were evaluated. Reduced daily activities were evaluated by the Scleroderma Health Assessment Questionnaire (SHAQ). There were no significant correlations between FXIII activity, MRSS, and SHAQ score. There were correlations between FXIII activity and Raynaud's phenomenon-related symptoms and a weak but not significant positive correlation with the level of pain. A significant correlation between VWF-Ag and lung-associated complaints (n = 56; p = 0.41, p < 0.0001) was found. Moreover, the study showed a correlation between VWF-Ag and MRSS (r [N = 48] = 0.4, p = 0.01), which means that higher VWF-Ag levels come along with more severe skin involvement. A trend toward a negative correlation between FXIII activity and VWF-Ag as marker of endothelial dysfunction was found (r [N = 56] = - 0.20, p = 0.15). In our cohort, there is no FXIII deficiency in patients with SSc. FXIII might have a role in improving cutaneous manifestations indirectly by means of a moderating influence on endothelial dysfunction. Further clinical evaluation is needed.

Targeting Fibrosis to Improve Cancer Outcomes

Abstract Scleroderma (SSc) is an idiopathic autoimmune connective tissue disease. The three hallmarks of SSc include 1) vasculopathy resulting in 2) progressive fibrosis or thickening of the skin, lungs, and internal organs and 3) aberrant immune infiltration. Fibrotic pulmonary involvement is the leading cause of death in SSc patients. Recent data from John Hopkins Scleroderma Center have shown a significantly increased risk of lung cancer in SSc patients. However, the mechanisms linking the two diseases are not well understood. Moreover, due to the close temporal relationship between SSc and lung cancer diagnosis, it is unclear whether lung fibrosis precedes tumorigenesis or conversely lung tumorigenesis precedes fibrosis. It has become evident that certain fibrotic diseases can progress towards cancer. Seemingly, non-alcoholic steatohepatitis or HBV/HCV infection-induced liver cirrhosis can progress to hepatocellular carcinoma. Vice versa, many solid tumors are fibrotic, and desmoplasia is referred to the pathological remodeling observed in the tumor microenvironment. There seems to be a tight link between fibrosis and cancer although the directionality of this progression is unknown. Moreover, several fibrotic processes involving the ß-catenin/Wnt, YAP/TAZ and hedgehog pathways in addition to fibrogenic growth factors (TGFß, VEGF, FGF) have been known to drive cancer. We are developing a murine model to study the mechanisms driving fibrosis to cancer progression in the lungs.

Calcinosis Cutis and Calciphylaxis in Autoimmune Connective Tissue Diseases.

Calcinosis represents a severe complication of several autoimmune disorders. Soft-tissue calcifications have been classified into five major types: dystrophic, metastatic, idiopathic, iatrogenic, and calciphylaxis. Autoimmune diseases are usually associated with dystrophic calcifications, including calcinosis cutis, occurring in damaged or devitalized tissues in the presence of normal serum levels of calcium and phosphate. In particular, calcinosis cutis has been described in dermatomyositis, polymyositis, juvenile dermatomyositis, systemic sclerosis, systemic lupus erythematosus, primary Sjögren's syndrome, overlap syndrome, mixed connective tissue disease, and rheumatoid arthritis. Calciphylaxis, a severe and life-threatening syndrome presenting with vascular calcifications and thrombosis, has also been associated with some autoimmune conditions. Due to the potentially disabling character of calcinosis cutis and calciphylaxis, physicians' awareness about the clinical presentation and management of these diseases should be increased to select the most appropriate treatment option and avoid long-term complications. In this review, we aim to analyze the clinical features of calcinosis cutis and calciphylaxis associated with autoimmune diseases, and the main treatment strategies evaluated up to now for treating this potentially disabling disease.

P064 Incidence and Clinical Outcomes of New-onset Autoimmune Connective Tissue Diseases after COVID-19 Infection- A Systematic Literature Review

Abstract Background/Aims Cases of new autoimmune and autoinflammatory conditions have been reported among COVID-19 survivors. A literature review on new-onset autoimmune connective tissue diseases (ACTDs) following infection with COVID-19 is lacking.This systematic literature review aimed to evaluate the potential association between COVID-19 infection and the development of new-onset ACTDs in adults. Methods Articles published until September 2022, investigating the association between COVID-19 infection and new-onset ACTDs were included. The “population” searched was patients with disease terms for autoimmune connective tissue diseases, including (but not limited to) systemic lupus erythematosus (SLE), Sjogren’s syndrome, systemic sclerosis (SSc), any idiopathic inflammatory myositis (IIM), anti-synthetase syndrome, mixed CTD and undifferentiated CTD (and related MeSH terms), with “intervention” as COVID-19 and related terms. For terms for COVID-19, a dedicated search strategy developed by the National Institute for Clinical Excellence was used.Medline, Embase, and Cochrane databases were searched, restricted to English-language articles only. Eligible articles were: case reports and series (of any sample size), observational studies, qualitative studies and randomised controlled trials. Patients developing ACTDs without prior COVID-19 or reporting flares of existing ACTDs were excluded. Information was extracted on patient demographics, new ACTDs’ onset time, clinical characteristics, COVID-19 and ACTD treatment, and COVID-19 and ACTDs outcomes. The protocol was registered in PROSPERO (CRD42022358750). Results After deduplication, 2239 articles were identified. After screening title and abstract, 2196 papers were excluded, with 43 proceeding to full-text screening. Ultimately, 28 articles (all single case reports) were included. Of the 28 included patients, 64.3% were female. The mean age was 51.1 years (range 20-89 years). The USA reported the most cases (9/28). ACTD diagnoses comprised: 11 (39.3%) IIM (including 4 cases of dermatomyositis); 7 (25%) SLE; 4 (14.3%) anti-synthetase syndrome; 4 (14.3%) SSc; 2 (7.1%) other ACTD (one diagnosed with lupus/MCTD overlap). Of eight, four (14.3%) patients (including that with lupus/MCTD) were diagnosed with lupus nephritis. The average onset time from COVID-19 infection to ACTD diagnosis was 23.7days. A third of the patients were admitted to critical care, one for ACTD treatment for SLE with haemophagocytic lymphohistiocytosis (14 sessions of plasmapheresis, rituximab and intravenous corticosteroids) and nine due to COVID-19. The majority (80%) of patients went into remission of ACTD following treatment, while two (10%) patients died- one due to macrophage activation syndrome associated with anti-synthetase syndrome and two from unreported causes. Conclusion Our results suggest a potential association between COVID-19 infection and new-onset ACTDs, predominantly in young females, reflective of wider CTD epidemiology. The aetiology and mechanisms by which ACTDs arise following COVID-19 infection remain unknown and require more robust epidemiological data. Disclosure K. Kouranloo: None. M. Dey: None. H. Elwell: None. A. Nune: None.

Localized Cutaneous Nodular Amyloidosis: A Specific Cutaneous Manifestation of Sjögren's Syndrome.

Primary localized cutaneous nodular amyloidosis (PLCNA) is a rare condition attributed to plasma cell proliferation and the deposition of immunoglobulin light chains in the skin without association with systemic amyloidosis or hematological dyscrasias. It is not uncommon for patients diagnosed with PLCNA to also suffer from other auto-immune connective tissue diseases, with Sjögren's syndrome (SjS) showing the strongest association. This article provides a literature review and descriptive analysis to better understand the unique relationship between these two entities. To date, 34 patients with PLCNA and SjS have been reported in a total of 26 articles. The co-existence of PLCNA and SjS has been reported, especially in female patients in their seventh decade of life with nodular lesions on the trunk and/or lower extremities. Acral and facial localization, which is a typical localization of PLCNA in the absence of SjS, seems to be much more unusual in patients with associated SjS.

Research progress on long-term developmental outcomes of offspring of pregnant women with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease that affects multiple organs and systems. It is more common in women of childbearing age. Compared with the general population, pregnant women with SLE are at a significantly increased risk of adverse perinatal outcomes such as preterm birth and intrauterine growth restriction. In addition, the offspring of SLE patients may also be adversely affected by in utero exposure to maternal autoantibodies, cytokines, and drugs. This article summarizes the long-term developmental outcomes of offspring of pregnant women with SLE in terms of the blood system, circulatory system, nervous system, and immune system.