Blood DNA virome associates with autoimmune diseases and COVID-19.

Aberrant immune responses to viral pathogens contribute to pathogenesis, but our understanding of pathological immune responses caused by viruses within the human virome, especially at a population scale, remains limited. We analyzed whole-genome sequencing datasets of 6,321 Japanese individuals, including patients with autoimmune diseases (psoriasis vulgaris, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), pulmonary alveolar proteinosis (PAP) or multiple sclerosis) and coronavirus disease 2019 (COVID-19), or healthy controls. We systematically quantified two constituents of the blood DNA virome, endogenous HHV-6 (eHHV-6) and anellovirus.

Induction of interleukin 21 receptor expression via enhanced intracellular metabolism in B cells and its relevance to the disease activity in systemic lupus erythematosus.

Objective: To elucidate the association between the changes in intracellular metabolism in the early stage of B cell activation and systemic lupus erythematosus (SLE) pathogenesis.

Methods: CD19 or CD19CD27 (naïve) cells from the peripheral blood of healthy controls and lupus patients were cultured under different stimuli. The changes in intracellular metabolism and signalling pathways in these cells were evaluated.

A case of Erdheim-Chester disease-a mimicker of IgG4-related disease and large vessel vasculitis.

The patient was a 57-year-old man who developed bilateral thigh pain and chest tightness one year ago. Chest CT scan showed reticular shadows, thickened interlobular septa in both lung fields, and pericardial effusion. Three months ago, his symptoms worsened.

An autopsy of a patient with polyarteritis nodosa who developed fatal intestinal perforation accompanied by systemic multiple aneurysms and arterial thrombosis.

The patient was a 48-year-old man who had developed acute myocardial infarction 3 years earlier. He started experiencing recurrent attacks of abdominal pain 2 years earlier. One month before the presentation, he developed perforative peritonitis, which was treated with right hemicolectomy.

The abundance of regulatory T cell subsets is associated with the clinical outcomes of sarcoidosis.

Objectives: Some patients with sarcoidosis achieve spontaneous remission, whereas others repeatedly experience relapse. We examined differences in the clinical course of active sarcoidosis according to peripheral blood immunophenotypes before treatment.

Methods: This retrospective study compared peripheral blood immunophenotypes between patients with active sarcoidosis (n=28) and healthy control subjects (n=10).

Efficacy, safety, and optimal intervention of belimumab for proliferative lupus nephritis patients in real-world settings: LOOPS registry.

Objectives: This study investigated the efficacy, safety, and predictive factors of belimumab (BEL) in induction therapy for patients with proliferative lupus nephritis (LN) in real-world settings.

Methods: Patients with biopsy-proven ISN/RPS class III or IV LN, with or without coexisting class V LN, who underwent standard of care (SoC), glucocorticoid (GC), and either mycophenolate mofetil or cyclophosphamide treatments were included. Participants were treated with SoC (SoC group, n = 32) or BEL and SoC (BEL+SoC group, n = 30).

Comparison of anti-IL-6 receptor and JAK inhibitors in patients with rheumatoid arthritis from the real-world practice FIRST study.

Objectives: A molecular-targeted drug that is suitable as the second choice for patients with rheumatoid arthritis (RA) who show an inadequate response to the first biological disease-modifying antirheumatic drug (bDMARD) is unknown. This study aimed to analyze the efficacy and safety of interleukin-6 receptor (IL-6Ri) and Janus kinase inhibitors (JAKis), often selected as molecular-targeted drugs for second or subsequent treatments.

Methods: The efficacy and safety of JAKis and IL-6Ri were compared using propensity score-based inverse probability of treatment weighting (PS-IPTW) using propensity scores after 26 weeks of therapy in patients with RA.

CT informs detection and treatment options in rheumatoid arthritis complicated by pulmonary non-tuberculous mycobacterial disease from the FIRST registry.

Objective: To investigate the early detection of pulmonary non-tuberculous mycobacterial (PNTM) disease by CT before the initiation of molecular-targeted therapeutic drugs in patients with rheumatoid arthritis (RA) and the efficacy and safety of combined treatment with antibiotics.

Methods: Patients with RA underwent chest CT before the introduction of molecular-targeted therapies in the Further Improvement of Rheumatoid arthritis Treatment registry. The primary endpoint was the number of patients who were detected by CT as having PNTM disease, complicating RA.

CCL19-Positive Lymph Node Stromal Cells Govern the Onset of Inflammatory Arthritis via Tropomyosin Receptor Kinase.

Objective: The study objective was to assess the role of CCL19 lymph node stromal cells of the joint-draining popliteal lymph node (pLN) for the development of arthritis.

Methods: CCL19 lymph node stromal cells were spatiotemporally depleted for five days in the pLN before the onset of collagen-induced arthritis (CIA) using Ccl19-Cre × iDTR mice. In addition, therapeutic treatment with recombinant CCL19-immunoglobulin G (IgG), locally injected in the footpad, was used to confirm the results.

Generation-Dependent Retention Rates and Reasons for Discontinuation of Molecular Targeted Therapies in Patients with Rheumatoid Arthritis: From FIRST Registry.

Introduction: The study aimed to optimize medical care for elderly patients with rheumatoid arthritis (RA) by examining the 3-year continuation rate of different molecular targeted therapies across age groups in Japan, which has a significant elderly population.

Methods: The study included patients with RA who started molecular targeted therapies between 2013 and 2019 and divided them into three age groups. The primary outcome was to assess the 3-year continuation rate of each drug and analyze reasons for treatment discontinuation using inverse probability of treatment weighting.

A case of glucocorticoid-resistant adult Still's disease complicated by pulmonary hypertension and interstitial lung disease.

Adult Still's disease (ASD) is rarely complicated by pulmonary hypertension (PH). A 76-year-old woman experienced ASD relapse with repeated exacerbation of PH and interstitial lung disease. Although she had been treated with immunosuppressive agents and pulmonary vasodilators, the ASD relapsed with fever, rash, increased inflammatory responses and exacerbated interstitial lung disease, and PH.

Precision medicine based on the phenotypic differences in peripheral T helper cells in patients with psoriatic arthritis: One year follow-up outcomes.

Purpose: We validated the one-year effectiveness of strategic treatment with biological disease-modifying anti-rheumatic drugs (bDMARDs) based on peripheral T-lymphocytic phenotyping and explored the impact of treatment on T helper lymphocytic phenotypes.

Methods: Ninety-seven patients were registered in this study. One-year treatment response was compared between the two groups: the strategic bDMARDs treatment group ( = 41), in which bDMARDs were selected based on peripheral blood lymphocyte analysis, and the standard bDMARDs treatment group ( = 56), in which the patients underwent no strategic selection of bDMARDs and phenotyping.

Safety and effectiveness of mepolizumab therapy in remission induction therapy for eosinophilic granulomatosis with polyangiitis: a retrospective study.

Objectives: To investigate the safety and effectiveness of mepolizumab (MPZ), an anti-interleukin-5 antibody, as remission induction therapy for severe eosinophilic granulomatosis with polyangiitis (EGPA).

Methods: The clinical courses of patients with severe EGPA over 6 months were retrospectively investigated and compared between patients treated with high-dose corticosteroid (CS) plus MPZ therapy (MPZ group, n = 7) and those treated with high-dose CS plus intravenous cyclophosphamide (IVCY) pulse therapy (IVCY group, n = 13). The primary endpoints were the MPZ retention rate and the IVCY completion rate.

Impact of serum interleukin-22 as a biomarker for the differential use of molecular targeted drugs in psoriatic arthritis: a retrospective study.

Background: We explored whether serum cytokines could be used as biomarkers for optimal use of tumor necrosis factor inhibitors (TNF-i) and interleukin (IL)-17 inhibitors (IL-17-i) in patients with psoriatic arthritis (PsA).

Methods: In cohort 1 (47 patients treated with IL-17-i [n=23] or TNF-i [n=24] for ≥1 year), we identified serum cytokines that predicted the achievement of Disease Activity in Psoriatic Arthritis-remission (DAPSA-REM), Psoriasis Area and Severity Index (PASI) 90, and Minimal Disease Activity after 1 year of TNF-i or IL-17-i therapy. Subsequently, we developed treatment strategies based on the identified cytokines; initiation of IL-17-i therapy in patients with low IL-22 concentrations (IL-22 <0.

Dawn of Precision Medicine in Psoriatic Arthritis.

The establishment of precision medicine is considered particularly important in heterogeneous autoimmune diseases (e.g., psoriatic arthritis, systemic lupus erythematosus), which reveal clinical and molecular heterogeneity.

A patient with eosinophilic granulomatosis with polyangiitis successfully weaned from corticosteroids through remission induction therapy with mepolizumab.

The patient was a 74-year-old man who was admitted to our hospital for fever, purpura, abdominal pain, and bilateral numbness. Although the patient tested negative for anti-neutrophil cytoplasmic antibody (ANCA), he presented with an elevated peripheral eosinophil count, increased inflammatory responses, duodenitis, cholecystitis, lung lesions, renal disorder, and peripheral neuropathy. The skin biopsy findings revealed vasculitis.

Nailfold microvascular abnormalities are associated with a higher prevalence of pulmonary arterial hypertension in patients with MCTD.

Objective: MCTD manifests with microvasculopathy and overlapping clinical features of SLE, SSc and idiopathic inflammatory myopathies (IIM). The aim of this study was to investigate the clinical significance of microvasculopathy in patients with MCTD using nailfold videocapillaroscopy (NVC).

Methods: Fifty patients with newly diagnosed and untreated MCTD were enrolled in this multicentre, prospective and observational study.

Efficacy and safety of high-dose of mycophenolate mofetil compared with cyclophosphamide pulse therapy as induction therapy in Japanese patients with proliferative lupus nephritis.

Objectives: To clarify the effectiveness and safety of induction therapy with mycophenolate mofetil (MMF) in patients with lupus nephritis (LN).

Methods: Patients with LN administered MMF (n = 35) or intravenous cyclophosphamide pulse therapy (IVCY) (n = 25) plus high-dose corticosteroids between July 2015 and June 2020 were included. MMF was increased from 2 to 3 g/day, with no adverse events (AEs).

Association of frailty on treatment outcomes among patients with suspected infection treated at emergency departments.

Background: The clinical frailty scale (CFS) score has been validated as a predictor of adverse outcomes in community-dwelling older people. Older people are at a higher risk of sepsis and have a higher mortality rate. However, the association of frailty on outcomes in patients with sepsis has not been completely examined.