ABSTRACT
Aging is a significant risk factor for autoimmunity, and many autoimmune diseases tend to onset during adulthood. We conducted an extensive analysis of CD4+ T cell subsets from 354 patients with autoimmune disease and healthy controls via flow cytometry and bulk RNA sequencing. As a result, we identified a distinct CXCR3midCD4+ effector memory T cell subset that expands with age, which we designated "age-associated T helper (THA) cells." THA cells exhibited both a cytotoxic phenotype and B cell helper functions, and these features were regulated by the transcription factor ZEB2. Consistent with the highly skewed T cell receptor usage of THA cells, gene expression in THA cells from patients with systemic lupus erythematosus reflected disease activity and was affected by treatment with a calcineurin inhibitor. Moreover, analysis of single-cell RNA sequencing data revealed that THA cells infiltrate damaged organs in patients with autoimmune diseases. Together, our characterization of THA cells may facilitate improved understanding of the relationship between aging and autoimmune diseases.
Subject(s)
Autoimmune Diseases , Lupus Erythematosus, Systemic , Humans , Adult , Autoimmunity , T-Lymphocytes, Helper-Inducer , T-Lymphocyte Subsets , Zinc Finger E-box Binding Homeobox 2/metabolismABSTRACT
Pulmonary hypertension (PH) is a serious condition in which there is an abnormally high pressure in the pulmonary arteries that can occur as a complication of connective tissue diseases. Although the relationship between PH and systemic lupus erythematosus or systemic sclerosis has been well-characterized, PH rarely occurs in patients with anti-synthetase syndrome (ASS), and little is known about the pathophysiology and clinical outcome of patients with ASS-PH. We herein report a patient with anti-Jo-1-positive ASS complicated by PH and discuss the treatment strategy through a review of previously reported cases.
Subject(s)
Connective Tissue Diseases , Hypertension, Pulmonary , Lupus Erythematosus, Systemic , Scleroderma, Systemic , Humans , Hypertension, Pulmonary/complications , Hypertension, Pulmonary/drug therapy , Connective Tissue Diseases/complications , Scleroderma, Systemic/complications , Lupus Erythematosus, Systemic/complications , Pulmonary ArteryABSTRACT
Protein-losing enteropathy (PLE) has been reported to be associated with various systemic autoimmune diseases. However, reports regarding PLE in ANCA-associated vasculitis (AAV) patients are limited. We herein aimed to describe the clinical characteristics of AAV with PLE. We conducted a retrospective chart review of patients who were diagnosed with AAV and who began treatment at the University of Tokyo Hospital between June 2003 and June 2020. Among 68 AAV patients, there were four patients (5.9%) with PLE, consisting of two patients with MPA, one patient with GPA, and one patient with EGPA. Clinical courses were described, and their data were compared with AAV patients without PLE. Demographic characteristics, disease activity, and the pattern of organ involvement were similar between patients with PLE and without PLE. Patients with PLE had hypocomplementemia more frequently than the patients without PLE (CH50 75.0% vs 1.8%, p < 0.001, C3 50.0% vs 1.8%, p = 0.01, C4 75.0% vs 3.5%, p = 0.001). Although hypoalbuminemia improved with immunosuppressive therapy for AAV, the improvement in hypoalbuminemia was slow in most cases. We also performed a systematic review on PLE associated with vasculitis. Thirteen reports were included, and Henoch-Schonlein Purpura patients with PLE also tended to have hypocomplementemia. In conclusion, PLE is a rare complication of AAV and complement system may associate with the mechanism of PLE.
Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Hypoalbuminemia , Protein-Losing Enteropathies , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Antibodies, Antineutrophil Cytoplasmic , Complement System Proteins , Humans , Hypoalbuminemia/complications , Protein-Losing Enteropathies/diagnosis , Protein-Losing Enteropathies/etiology , Protein-Losing Enteropathies/therapy , Retrospective StudiesABSTRACT
The frequent prescription of antimicrobials, such as at discharge from the emergency department, calls for optimizing this practice through modifying physicians' prescribing behavior. A 1-year, multifaceted intervention implemented in an emergency department decreased the mean monthly antimicrobial prescription rate at discharge and increased the proportion of appropriate prescriptions.
Subject(s)
Anti-Infective Agents , Patient Discharge , Anti-Infective Agents/therapeutic use , Emergency Service, Hospital , Humans , Practice Patterns, Physicians' , PrescriptionsABSTRACT
Due to its rarity and the limited literature, the clinicopathological characteristics of peripheral nerve involvement in immunoglobulin G4 (IgG4)-related disease are unknown. We present two cases of IgG4-related disease, accompanied by peripheral neuropathy, presenting as unilateral ptosis (case 1) and sclerosing cholangitis (case 2), respectively. In both cases, sural nerve biopsy indicated vasculitis as the underlying pathophysiology; the peripheral neuropathy was refractory to corticosteroid therapy. In contrast to the previously proposed pathomechanism of IgG4-related neuropathy (direct lymphoplasmacytic infiltration), the pathological findings in our cases suggest that vasculitis occurs secondary to systemic autoimmune conditions.
