Lung fibrosis in autoimmune diseases and hypersensitivity: how to separate these from idiopathic pulmonary fibrosis.

Lung involvement in autoimmune diseases (AID) is uncommon, but may precede other organ manifestations. A diagnostic problem is chronicity presenting with lung fibrosis. A new category of interstitial pneumonia with autoimmune features for patients with clinical symptoms of AID and presenting with usual interstitial pneumonia (UIP) enables antifibrotic treatment for these patients. Hypersensitivity pneumonia (HP) and other forms of lung fibrosis were not included into this category. As these diseases based on adverse immune reactions often present with unspecific clinical symptoms, a specified pathological diagnosis will assist the clinical evaluation. We aimed to establish etiology-relevant differences of patterns associated with AID or HP combined with lung fibrosis. We retrospectively evaluated 51 cases of AID, and 29 cases of HP with lung fibrosis, and compared these to 24 cases of idiopathic pulmonary fibrosis (UIP/IPF). Subacute AID and HP most often presented with organizing pneumonia (OP), whereas chronicity was associated with UIP. Unspecified fibrosis was seen in a few cases, whereas NSIP pattern was rare. In 9 cases, the underlying etiology could not be defined. Statistically significant features differentiating chronic AID or HP from UIP/IPF are lymphocytic infiltrations into myofibroblastic/fibroblastic foci. Other features significantly associated with AID and HP were granulomas, isolated Langhans giant cells, and protein deposits, but seen in only a minority of cases. A combination of UIP with one of these features enabled a specific etiology-based diagnosis. Besides the antifibrotic drug regimen, additional therapies might be considered.

Impact of Rheumatoid Arthritis on Hospitalized Inflammatory Bowel Disease Patients: Study of Demographics, Clinical Characteristics and Outcomes.

Background Inflammatory bowel disease (IBD), comprising ulcerative colitis and Crohn's disease gives rise to chronic intestinal inflammation. Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by joint and systemic inflammation. IBD is often linked with various autoimmune diseases, with RA being one of the most common. The coexistence of IBD and RA results in an increased inflammatory state, significantly compromising quality of life. Understanding the epidemiological and clinical characteristics of IBD patients with RA is essential for optimizing their management and improving outcomes. Methodology This retrospective observational study utilized data from the National Inpatient Sample (NIS) database from 2016 to 2020. Patients aged 18 years and older with a primary discharge diagnosis of IBD were included. This population was subdivided into two groups based on the presence and absence of RA. The primary objective was to compare outcomes between hospitalized IBD patients with and without RA. Key outcomes assessed included mortality rates, hospital length of stay (LOS), and total hospital charges. Secondary outcomes included the prevalence of comorbidities and IBD-related complications. Results From 2016 to 2020, a total of 455,655 hospitalized IBD patients were identified, among whom 10,590 (2.32%) had an underlying diagnosis of RA. Patients with both IBD and RA were significantly older than those without RA (mean age 52.21 vs. 45.72 years, p < 0.001) and had a higher proportion of females (72.51% vs. 53.27%, p < 0.01). RA patients exhibited a greater risk of cardiovascular risk factors compared to non-RA patients, including diabetes [adjusted odd ratio (aOR ) 1.12 (1.09-1.16)], hypertension [aOR 1.19 (1.07-1.33)], hyperlipidemia [aOR 1.61 (1.60-1.63)], chronic kidney disease stage 1-4 [aOR 1.35 (1.29-1.41)], coronary artery disease [aOR 1.67 (1.65-1.69)], and heart failure [aOR 1.45 (1.43-1.48)]. However, there were no significant differences in the rates of IBD-related complications or in-hospital mortality between the two groups. The mean hospital LOS was 5.15 days for RA patients and 4.95 days for non-RA patients (p = 0.08), with similar total hospital charges ($48,442.7 vs. $48,720.3, p = 0.88). Conclusion This study shows hospitalized IBD patients with and without RA have similar hospitalization outcomes, however, patients with RA have a higher cardiovascular risk. The findings emphasize the importance of integrated, multidisciplinary management approaches for these patients, addressing not only their gastrointestinal and rheumatologic conditions but also their associated comorbidities.

Juvenile Dermatomyositis Presenting As Generalized Poikiloderma: A Case Report.

Juvenile dermatomyositis (JDM) is a chronic autoimmune inflammatory disorder and is considered the most common form of idiopathic inflammatory myopathies. JDM primarily affects the skin and the skeletal muscles. Characteristic signs and symptoms include Gottron papules, heliotrope rash, calcinosis cutis, and symmetrical proximal muscle weakness. However, JDM presenting with generalized scaly poikeloderma is an unfamiliar presentation. Herein we report a 14-month-old female toddler presented with generalized progressive asymptomatic scaly mottled violaceous patches (poikilodermatous) that started when she was seven months old. Her lab results were unremarkable. She was diagnosed with poikilodermatous skin rash with a differential diagnosis of Amyopathic dermatomyositis, poikilodermatous genodermatosis, and patch-stage mycosis fungoides. She was prescribed moisturizer creams only. A year later, during a follow-up, she presented with a full picture of JDM, with a history of scaly poikilodermatous skin patches that became more widespread, frequent choking during oral intake, and not being able to stand and sit unsupported. Laboratory workup was significant for low WBC and hemoglobin counts, along with elevated CPK, LDH, ferritin, CRP, and ESR levels. MRI revealed the right anterior thigh and vastus lateralis subcutaneous edema. Therefore, the child was diagnosed and treated as a case of JDM.

A Case of Chronic Undiagnosed 2:1 Isolated Atrial Flutter in a Patient With an Autoimmune Disease.

Atrial flutter (AFL) is typically associated with structural heart diseases or metabolic abnormalities. However, isolated symptomatic AFL, which occurs without abnormal heart anatomy, remains a rare occurrence and is underrepresented in the literature. This case report highlights the significance of recognizing and investigating symptoms suggestive of arrhythmias, especially in patients with autoimmune conditions.

Accurate Machine Learning Model to Diagnose Chronic Autoimmune Diseases Utilizing Information From B Cells and Monocytes.

Heterogeneity and limited comprehension of chronic autoimmune disease pathophysiology cause accurate diagnosis a challenging process. With the increasing resources of single-cell sequencing data, a reasonable way could be found to address this issue. In our study, with the use of large-scale public single-cell RNA sequencing (scRNA-seq) data, analysis of dataset integration (3.1 × 105 PBMCs from fifteen SLE patients and eight healthy donors) and cellular cross talking (3.8 × 105 PBMCs from twenty-eight SLE patients and eight healthy donors) were performed to identify the most crucial information characterizing SLE. Our findings revealed that the interactions among the PBMC subpopulations of SLE patients may be weakened under the inflammatory microenvironment, which could result in abnormal emergences or variations in signaling patterns within PBMCs. In particular, the alterations of B cells and monocytes may be the most significant findings. Utilizing this powerful information, an efficient mathematical model of unbiased random forest machine learning was established to distinguish SLE patients from healthy donors via not only scRNA-seq data but also bulk RNA-seq data. Surprisingly, our mathematical model could also accurately identify patients with rheumatoid arthritis and multiple sclerosis, not just SLE, via bulk RNA-seq data (derived from 688 samples). Since the variations in PBMCs should predate the clinical manifestations of these diseases, our machine learning model may be feasible to develop into an efficient tool for accurate diagnosis of chronic autoimmune diseases.

Prevention of EAE by tolerogenic vaccination with PEGylated antigenic peptides.

BACKGROUND: Therapeutic treatment options for chronic autoimmune disorders such as multiple sclerosis (MS) rely largely on the use of non-specific immunosuppressive drugs, which are not able to cure the disease. Presently, approaches to induce antigen-specific tolerance as a therapeutic approach; for example, by peptide-based tolerogenic 'inverse' vaccines have regained great interest. We have previously shown that coupling of peptides to carriers can enhance their capacity to induce regulatory T cells in vivo. METHOD: In this present study, we investigated whether the tolerogenic potential of immunodominant myelin T-cell epitopes can be improved by conjugation to the synthetic carrier polyethylene glycol (PEG) in an experimental autoimmune encephalomyelitis (EAE) mouse model for chronic MS (MOG C57BL/6). RESULTS: Preventive administration of the PEGylated antigenic peptide could strongly suppress the development of EAE, accompanied by reduced immune cell infiltration in the central nervous system (CNS). Depletion of regulatory T cells (Tregs) abrogated the protective effect indicating that Tregs play a crucial role in induction of antigen-specific tolerance in EAE. Treatment during the acute phase of disease was safe and did not induce immune activation. However, treatment at the peak of disease did not affect the disease course, suggesting that either induction of Tregs does not occur in the highly inflamed situation, or that the immune system is refractory to regulation in this condition. CONCLUSION: PEGylation of antigenic peptides is an effective and feasible strategy to improve tolerogenic (Treg-inducing) peptide-based vaccines, but application for immunotherapy of overt disease might require modifications or combination therapies that simultaneously suppress effector mechanisms.

Icariin alleviates rheumatoid arthritis via regulating miR-223-3p/NLRP3 signalling axis.

Rheumatoid arthritis (RA) is considered to be a chronic autoimmune disease, pathogenesis of RA is complex and effective treatments for RA is still lacking. Previous studies found that microRNAs (miRNAs) play important roles in the pathogenesis of RA, and miR-223-3p is considered to be one of the possible biomarkers of RA. Recent studies have revealed that icariin alleviates RA in murine models, but the underlying mechanism needs to be further investigated. MiR-223-3p expression levels in fibroblast-like synoviocyte (RA-FLS) and patients with RA were quantified by qRT-PCR, cell proliferation was analyzed by CCK-8 and BrdU assay. Cell apoptosis was assessed by flow cytometry and western blotting. TNF-α, IL-1ß and IL-6 concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Dual luminescence-based reporter gene assay was conducted to confirm the possible interaction between miR-223-3p and NLRP3. Icariin inhibits proliferation and inflammation cytokines secretion, promotes apoptosis of RA-FLS cells and upregulated the expression of miR-223-3p. MiR-223-3p targets to 3'-UTR of NRLP3 and regulates its expression. MiR-223-3p inhibitor reversed the effect of icariin on RA-FLS cells function. Additionally, anti-RA activity of icariin was restored by NLRP3 inhibitor MCC950 in miR-223-3p knockdown RA-FLS cells. Icariin inhibits proliferation and inflammation, promotes apoptosis of RA-FLS cells by regulating miR-223-3p/NLRP3 signalling, which may serve as a potential therapeutic target to alleviate RA.