Pregnancy fundamentally reshapes maternal immunity, creating a state of immune tolerance that simultaneously increases susceptibility to infections. In women with rheumatic diseases (RDs), this vulnerability is further amplified by underlying autoimmune dysregulation and immunosuppressive therapies. Infectious comorbidities in this population represent a major challenge as they may precipitate rheumatic disease flares, contribute to maternal morbidity, and adversely affect pregnancy, including miscarriage, preterm birth, fetal growth restriction, and neonatal complications. This review aims to overview current evidence on infectious comorbidities in pregnant patients with RDs, with a focus on rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, and primary Sjögren syndrome. Disease-specific infection patterns and their impact on maternal and fetal outcomes are discussed. Literature searches were performed in Medline/PubMed, Scopus, Web of Science, and Directory of Open Access Journals (DOAJ) to identify documents on infections, prevention, and outcomes in pregnant women with RDs published up to September 2026. The influence of pregnancy-related immune modulation and immunosuppressive treatments, including corticosteroids, disease-modifying antirheumatic drugs, and biologic agents, on infection risk is examined. Preventive strategies, including preconception counseling, vaccination, targeted screening, and multidisciplinary management, are also addressed. Available evidence suggests that infectious comorbidities remain underrecognized in pregnancy counseling for women with RDs. Early risk stratification, individualized adjustment of immunosuppressive therapy, and close collaboration between rheumatologists, obstetricians, and infectologists are essential to optimize maternal and fetal outcomes.

Rheumatological diseases (RDs) are characterized by autoimmune-mediated organ damage, with the lungs being an important target organ. Almost all compartments of the pulmonary system may be involved, with considerable heterogeneity in the frequency, severity, and spectrum of pulmonary manifestations. This heterogeneity may result in delayed diagnosis and treatment, leading to adverse outcomes. The objective of this study was to characterize the clinical, demographic, serological, and radiological features of pulmonary manifestations across a spectrum of rheumatic diseases. This cross-sectional study was conducted between 2016 and 2023 at a tertiary care center in New Delhi, India. Patients aged ≥18 years with a diagnosed or suspected RD and pulmonary manifestations were included. Patients who did not fulfill the American College of Rheumatology/European League against Rheumatism classification criteria for RD or the American Thoracic Society/European respiratory Society criteria for interstitial pneumonia with autoimmune features (IPAF), as well as those with chronic hypersensitivity pneumonitis or sequelae of previous pulmonary infections, were excluded. Of the 783 patients screened, 170 were diagnosed with rheumatology-associated lung disease (RALD) or IPAF. The mean age was 44.3 years, with a marked female predominance (85%). Rheumatoid arthritis (RA) and systemic sclerosis (SSc) accounted for 70% of cases, followed by IPAF, overlap syndromes, Sjögren syndrome (SjS), systemic lupus erythematosus (SLE), and idiopathic inflammatory myositis. Twenty-six patients with idiopathic interstitial pneumonia were reclassified as having IPAF, one of whom subsequently progressed to RA. Pulmonary symptoms preceded the diagnosis of RD in 13.6% of patients, occurred concurrently with the diagnosis in 17%, and developed during the course of RD in 69.4%. Antinuclear antibodies and rheumatoid factor were the most commonly detected autoantibodies, while anti-aminoacyl-tRNA synthetase antibodies were identified in 11 patients. RA demonstrated the broadest spectrum of pulmonary manifestations. Interstitial lung disease was the predominant pulmonary manifestation across all RDs except SLE. Non-specific interstitial pneumonia and usual interstitial pneumonia patterns accounted for 87% of cases. Other pulmonary manifestations included infections in RA and SLE; vascular and pleural involvement in RA, SSc, and SLE; and airway involvement in RA and SjS. Pulmonary manifestations may precede, coincide with, or develop after the onset of systemic features in RDs. Comprehensive pulmonary evaluation and collaborative care involving rheumatologists and pulmonologists may facilitate earlier diagnosis and optimize the management of RALDs.

Skin fibrosis is increasingly recognized as an important component of chronic inflammatory skin diseases, contributing to dermal thickening, tissue stiffness, and persistent functional impairment. Although transforming growth factor-β (TGF-β) has long been considered the central mediator of fibrosis, accumulating evidence indicates that interleukin-13 (IL-13), a key cytokine of type 2 immunity, plays a pivotal role in linking chronic inflammation to fibrotic remodeling. Unlike classical scar formation, IL-13-associated fibrosis is characterized by sustained immune activation, continuous extracellular matrix remodeling, and residual tissue plasticity, suggesting that it represents a dynamic and potentially reversible process. In this review, we summarize the current understanding of the mechanisms by which IL-13 promotes skin fibrosis. We discuss direct activation of fibroblasts through the IL-13Rα1/STAT6 pathway, dysregulation of extracellular matrix synthesis and degradation, neuroimmune interactions involving chronic itch and mechanotransduction, macrophage-fibroblast crosstalk, and emerging evidence for fibroblast memory mediated by epigenetic remodeling. Furthermore, we compare the pathological features of IL-13-associated fibrosis across representative skin diseases, including atopic dermatitis, prurigo nodularis, systemic sclerosis, and keloids. This conceptual framework provides a unified perspective on the diverse roles of IL-13 in cutaneous fibrosis and highlights the importance of integrating immunological, mechanical, and stromal mechanisms.

This article will discuss the oral mucosal and salivary gland manifestations of several rheumatologic diseases including autoimmune conditions such as Sjogren syndrome and systemic scleroderma as well as other inflammatory conditions such as lupus erythematosus and granulomatosis with polyangiitis.

This reflective article, written collaboratively by 4 people living with multiple sclerosis (MS)-Johanna Hising DiFabio, Meredith O'Brien, Jennifer Southard, and Danny van Leeuwen-with Mary Hennings of the Society for Participatory Medicine, distills insights shared at a March 2025 event cohosted with Northeastern University's Bouvé College of Health Sciences. The panelists speak as experts on their own lived experience, tracing the arc from diagnosis to what they call "optimal living" with a complex, unpredictable disease. The piece begins with the diagnostic journey itself, describing a "double trauma": the anguish of unexplained physical decline before diagnosis, followed by the weight of confronting a confirmed chronic illness. The authors argue that how clinicians deliver and support a diagnosis determines whether patients end up isolated or drawn into genuine partnership with their care team. A central theme is the search for the right clinician fit-not just competence, but shared communication style and mutual respect for the patient's expertise in their own life. The authors describe practices that support this, such as setting the visit agenda in advance through patient portals, and stress that patient engagement styles vary: some patients want deep involvement in research, while others prefer to delegate, but all need a clinician who genuinely listens. The article expands the notion of a care team beyond medical clinicians, describing three layers: the medical core, a complementary team (bodywork, movement, nutrition specialists), and a personal network of family and friends providing emotional support. It also names systemic frictions, like patients having to relay information among clinical specialists who don't communicate with each other. A recurring message is resisting being reduced to the disease. The authors describe both the comfort and sting of comments like being told they "don't look sick." They also share personal strategies for preserving identity and quality of life, from adapting a musical instrument to accommodate physical limitations, to writing and publishing patient narratives, to using organizational resources like the National MS Society to navigate research and advocacy. The article closes with practical counsel for newly diagnosed patients: stay engaged, insist on true clinical partnership, build a broad support ecosystem, and protect the personal choices that give life meaning. It affirms the core principle of participatory medicine-that patients and clinicians grow together, with the patient retaining ownership of their own body and life.

Autophagy-related (ATG) proteins orchestrate canonical autophagy and related pathways, including LC3-associated phagocytosis (LAP). Autophagy and LAP play essential roles in immune homeostasis and regulation. Systemic sclerosis (SSc) is an autoimmune disease of unknown etiology characterized by progressive fibrosis affecting the skin and multiple internal organs, together with profound immune dysregulation. ATG alleles have been proposed as genetic susceptibility factors for SSc, suggesting that defects in autophagy-related pathways may contribute to the disease pathogenesis. We investigated whether canonical autophagy and/or LAP are altered in immune cells from patients with SSc. Autophagy was assessed by measuring LC3-II levels in circulating cells from SSc patients and controls, and autophagic flux was evaluated by flow cytometry following lysosomal inhibition. We then generated monocyte-derived macrophages and performed phagocytosis assays to assess the LAP activity. We evaluated the phagocytic capacity using IgG-coated beads that trigger LAP through Fcγ receptor engagement and measured the proportion of LC3-positive phagosomes (LAPosomes). No major defects in canonical autophagy were found in lymphocytes and monocytes isolated from the peripheral blood of patients with SSc. In contrast, monocyte-derived M0 macrophages from patients with SSc exhibited impaired LC3-associated phagocytosis. Impaired LAP in macrophages may contribute to the defective efferocytosis observed in SSc, thereby promoting persistent inflammation and fibrosis. Our findings identify LAP as a previously unrecognized pathway altered in SSc and suggest that therapeutic strategies aimed at restoring LAP activity may represent a novel approach for disease treatment.

Neurodegenerative diseases (NDs) affect more than 55 million people worldwide, with this number projected to exceed 139 million by 2050 due to population aging. Alzheimer's disease (AD) accounts for 60-70% of dementia cases, while Parkinson's disease (PD) affects over 10 million individuals globally, highlighting the growing clinical and socioeconomic burden of these progressive neurological disorders. Effective treatment of AD, PD, amyotrophic lateral sclerosis (ALS), and related central nervous system disorders remains hindered by the blood-brain barrier (BBB), poor brain accumulation, rapid systemic clearance, and off-target toxicity. RVG29, a 29-amino-acid peptide derived from rabies virus glycoprotein, has emerged as a promising brain-targeting ligand because of its high affinity for nicotinic acetylcholine receptors expressed on neuronal and brain endothelial cells. This review critically examines the mechanisms underlying RVG29-mediated receptor-dependent BBB transcytosis, intracellular trafficking, and neuronal uptake. Furthermore, it comprehensively evaluates RVG29-functionalized lipid nanoparticles, polymeric nanoparticles, exosomes, biomimetic nanocarriers, micelles, inorganic nanostructures, and hybrid systems with respect to their physicochemical characteristics, targeting efficiency, therapeutic efficacy, and safety. Collectively, these nanocarriers demonstrate enhanced BBB penetration, increased drug accumulation in diseased brain regions, and efficient delivery of small molecules, genes, mRNA, and siRNA. By modulating oxidative stress, neuroinflammation, protein aggregation, ferroptosis, and mitochondrial dysfunction, RVG29-engineered nanocarriers provide significant neuroprotection with favorable biocompatibility and minimal immunogenicity. Despite these advances, challenges related to large-scale manufacturing, peptide stability, regulatory approval, and long-term biosafety must be addressed to facilitate their clinical translation as precision neurotherapeutics.

Tolerogenic dendritic cell (tolDC) vaccines are a promising antigen-specific therapy for multiple sclerosis (MS), yet their efficacy is limited by poor homing to secondary lymphoid organs and rapid loss of the tolerogenic phenotype in native inflamed lymph nodes. Here, we developed a 3D-printed tolerogenic artificial lymph node (tol-aLN) that creates a protected immune niche for durable tolerance induction. tolDCs were loaded onto a porous gelatin methacrylate scaffold engineered for sustained C-C motif chemokine ligand 21 (CCL21) release, recruiting naïve CD4[+] T cells and shielding tolDCs from an inflammatory lymph node. Geometric optimization of an orthogonal lattice scaffold enhanced spatially confined DC-T cell interactions, promoting robust and stable induction of regulatory T cells (Treg cells). In experimental autoimmune encephalomyelitis (EAE), tol-aLN implantation attenuated disease even at advanced stages by inducing antigen-specific Foxp3[+] Treg cells that trafficked to the spleen, lymph nodes, and central nervous system (CNS). Conditional Treg cell depletion abolished therapeutic efficacy, indicating that Treg cells are necessary mediators of tol-aLN-induced protection. Long-term studies revealed sustained remission without impairing systemic immunity. In a myelin oligodendrocyte glycoprotein (amino acids 1 to 125) (MOG1-125)-induced EAE model, multivalent tol-aLN also efficiently suppressed inflammatory B cells and autoantibody production, reprogramming CNS B cells toward a regulatory state. Single-cell transcriptomics further revealed a global reduction in interferon-stimulated gene activity and restoration of homeostatic microglial phenotypes. Collectively, tol-aLN offers a scalable, antigen-specific platform for immune tolerance and CNS protection, with translational potential for MS and other autoimmune diseases.