Immunological Medicine最新文献

To investigate the potential association between COVID-19 vaccination and Vogt-Koyanagi-Harada (VKH) syndrome, offering novel insights for the diagnosis and management of vaccine-related ocular disorders. A case report combined with a literature review was conducted. A 19-year-old male developing VKH after receiving the second dose of an inactivated COVID-19 vaccine was analyzed. Clinical features, treatment outcomes (glucocorticoid therapy with 2-year follow-up), and literature-based comparisons were evaluated. PubMed-indexed cases of vaccine-associated VKH were systematically reviewed, and causality was assessed using the Naranjo Adverse Drug Reaction Probability Scale. The patient presented with bilateral blurred vision 14 days post-vaccination, diagnosed as VKH with retinal neuroepithelial detachment via fluorescein angiography (FFA) and optical coherence tomography (OCT). Oral prednisone (starting at 60 mg/day, tapered gradually)restored visual acuity to near-normal levels (OD: 20/40, OS: 20/33), consistent with the patient's reported baseline vision. Within 8 weeks, with no recurrence during follow-up. Literature analysis revealed vaccine-associated VKH symptoms typically emerged at a median of 8 days post-vaccination, aligning with the WHO's 40-day adverse event monitoring window. A Naranjo score of 4 indicated a probable vaccine-triggered immune response. COVID-19 vaccines may induce VKH via immune dysregulation mechanisms, particularly in genetically predisposed individuals. Although causality remains unconfirmed, clinicians should maintain vigilance for acute bilateral uveitis post-vaccination. Glucocorticoid therapy demonstrates efficacy in symptom resolution and relapse prevention. Enhanced active surveillance and mechanistic studies on vaccine-related ocular adverse events are warranted.

Multicentric Castleman disease (MCD) is a rare and complex lymphoproliferative disorder marked by multiple lymph node enlargement, characteristic histopathological features, and systemic inflammation driven by excessive interleukin-6 (IL-6) production. MCD can occasionally coexist with other autoimmune diseases, but the therapeutic approach in such cases remains poorly defined. Here, we present the first documented case of MCD complicated by both rheumatoid arthritis (RA) and Sjögren's disease (SjD), where all conditions were successfully treated with tocilizumab (TCZ) monotherapy, an IL-6 receptor antagonist. Furthermore, a literature review identified two previously reported cases of MCD with either RA or SjD, all of which showed favorable responses to TCZ. Our findings highlight the potential of TCZ as an effective therapeutic option for patients with MCD in the context of coexisting autoimmune disorders, offering new hope for managing these challenging clinical scenarios.

This study aims to assess muscle strength recovery in patients with idiopathic inflammatory myopathy (IIM) with three myositis-specific autoantibodies (MSAs). Forty-eight IIM patients (19 with anti-TIF1-γ Ab, 21 with anti-ARS Ab, and 8 with anti-SRP Ab) were included. Physical exercise began one week after starting medication. Muscle strength was measured using a hand held dynamometer. CK levels, muscle strength recovery, manual muscle test 8 (MMT8), and the Barthel index (BI) scores were evaluated before and after treatment among patients with anti-TIF1-γ, anti-ARS or anti-SRP Abs. CK levels decreased after one week of medication, and physical exercise did not worsen muscle involvement. Patients with anti-TIF1-γ and anti-ARS Abs exhibited rapid muscle strength improvement, while those with anti-SRP Ab had slower recovery. MMT8 followed a similar trend. BI scores significantly improved in patients with anti-TIF1-γ and anti-ARS Abs. All eight patients with anti-SRP Ab achieved a BI score of 100 despite no significant changes due to high variability. Muscle strength improved significantly, even in patients with a BI score ≤ 60. Muscle strength was recovered regardless of their MSA profile, and physical exercise may be safe for restoring muscle strength.

Anifrolumab, a monoclonal antibody against type I interferon (IFN) receptor, has shown high efficacy against systemic lupus erythematosus (SLE) in clinical trials. Although rapid effects of anifrolumab against cutaneous manifestations of SLE have been reported, efficacy has still been considered to take a month or more, and shorter-term efficacy has not been described. A 29-year-old Japanese woman developed fever, erythema on the trunk and both upper and lower extremities, cytopenia, pericardial effusion, and acute confusional state and was diagnosed with SLE. Intravenous methylprednisolone pulse therapy followed by oral prednisolone at 50 mg/day improved her confusional state. Intravenous cyclophosphamide at 500 mg was added, and prednisolone was reduced to 40 mg/day. Fever and erythema on the upper extremities recurred shortly afterwards. Skin biopsy revealed panniculitis. After intravenously administering a single 300-mg dose of anifrolumab, fever resolved within a day, and erythema entirely disappeared within about 2 weeks. The serum IFN-α concentration decreased significantly after a single infusion of anifrolumab. Anifrolumab infusions every 4 weeks were continued, then prednisolone was tapered to 1 mg/day under anifrolumab therapy over 22 months. Anifrolumab may provide improvement on a daily basis even in patients refractory to the standard of care.

Long COVID has emerged as a significant global health issue, affecting individuals across a wide spectrum of initial disease severity. While its definition and prevalence vary across studies, persistent symptoms such as fatigue, cognitive dysfunction, respiratory difficulties, and cardiovascular complications have been widely reported. Multiple pathophysiological mechanisms have been proposed, including incomplete viral clearance, reactivation of latent viruses, immune dysregulation, autoimmunity, endothelial dysfunction, microbiome alterations, and mitochondrial impairment. These interconnected processes are thought to contribute to chronic inflammation and multi-organ disease. To date, there are no established therapies for Long COVID, and management primarily focuses on symptomatic relief and rehabilitation. Vaccination has been shown to reduce the incidence of Long COVID, and emerging strategies, including antiviral agents, immune-modulating therapies, microbiome restoration, and mitochondria-targeted interventions, are under investigation. This review summarizes the current understanding of the epidemiology, pathophysiology, organ-specific manifestations, and potential therapeutic approaches for Long COVID, aiming to provide insights into future research directions and clinical management strategies.

This phase 3 open-label study (jRCT2031210457; NCT05150340; January 2022-August 2023) evaluated pharmacokinetics, safety and tolerability, and efficacy of recombinant hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG) 10% in Japanese patients with primary immunodeficiency diseases (PID) transitioning from intravenous immunoglobulin (IVIG) or conventional SCIG (cSCIG). Patients received fSCIG 10% (HyQvia^®) with dose ramp-up (Epoch 1) and 3- or 4-week dosing intervals (Epoch 2; 24 weeks). Assessments included IgG trough levels, infusion-related tolerability, validated acute serious bacterial infections (VASBIs), and treatment-emergent adverse events (TEAEs). Sixteen patients completed the study (median age: 21 years; range: 5-62). Prior treatments included cSCIG (62.5%), IVIG (31.3%), and SCIG (human) 20% solution (Ig20Gly; Cuvitru^®) (6.3%). Geometric mean IgG trough levels during the evaluation period (Epoch 2) remained stable across all visits (1254-1351 mg/dL, 3-week dosing; 874-937 mg/dL, 4-week dosing). No tolerability events or VASBIs were observed. Annual infection rate was 2.74 per patient-year. TEAEs related to fSCIG 10% occurred in 68.8% of patients, all mild or moderate. No serious TEAEs related to fSCIG 10% or deaths occurred. No TEAEs led to study discontinuation. fSCIG 10% effectively maintained IgG levels, prevented infections, and was well tolerated in Japanese patients with PID transitioning from IVIG or cSCIG.

Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (DM)-associated interstitial lung disease (ILD) is a rapidly progressive and life-threatening condition that often requires aggressive immunosuppressive therapy, including Janus kinase (JAK) inhibitors, whose safety profile remains incompletely understood. We report an extremely rare case of secondary pulmonary alveolar proteinosis (PAP) that developed during tofacitinib treatment for multidrug-refractory anti-MDA5 antibody-positive DM-associated ILD. A 74-year-old Japanese woman with rapidly progressive DM-associated ILD was treated with high-dose glucocorticoids, intravenous cyclophosphamide, and cyclosporine, followed by tofacitinib due to an insufficient response. Although the ILD initially improved, she later developed progressive elevation of serum KL-6 levels and diffuse ground-glass opacities on chest computed tomography despite only mild respiratory symptoms. Transbronchial lung biopsy revealed periodic acid-Schiff-positive material within the alveolar spaces, and serum anti-granulocyte-macrophage colony-stimulating factor antibodies were negative, leading to a diagnosis of secondary PAP. Discontinuation of tofacitinib alone resulted in rapid clinical and radiological improvement. This case highlights PAP as a rare, potentially reversible complication during JAK inhibitor therapy in anti-MDA5 antibody-positive DM-associated ILD and underscores the importance of considering PAP when elevated KL-6 levels and radiological abnormalities occur despite only mild respiratory symptoms.

The clinical significance of serum lysozyme in sarcoidosis remains unclear. This study aimed to evaluate the clinical characteristics and kidney function of sarcoidosis patients with elevated serum lysozyme. We retrospectively analyzed 28 patients with sarcoidosis and measured levels of serum lysozyme. Clinical characteristics, laboratory data, and estimated glomerular filtration rate (eGFR) were evaluated. Median age was 57 years (interquartile range, 43-70 years), and 21% were men. High serum lysozyme levels were associated with a greater number of organ involvements (median 4 vs. 2, p = 0.022) and more frequent renal involvement (50 vs. 7%, p = 0.033). Serum lysozyme levels correlated inversely with eGFR (r = -0.814). Median serum lysozyme level was significantly higher in patients with renal sarcoidosis (RS) (30.2 μg/mL) than in non-RS patients (9.5 μg/mL, p = 0.003). Prominent intracytoplasmic lysozyme staining in proximal tubular epithelial cells was observed in the kidney of RS patients. Multiple regression analysis identified serum lysozyme as an independent risk factor for eGFR decline. Elevated serum lysozyme in sarcoidosis was associated with multiorgan involvements and renal impairment. Lysozyme may contribute to tubulointerstitial injury in RS, potentially through tubular reabsorption and cytotoxic effects. Further studies are warranted to clarify the role of lysozyme in the pathogenesis of RS.

We report a case of cold agglutinin disease (CAD) considered as other iatrogenic immunodeficiency-associated lymphoproliferative disorder (OIIA-LPD) in a patient with rheumatoid arthritis (RA) and Sjögren's disease. A 69-year-old woman developed hemolytic anemia and renal dysfunction after long-term methotrexate and infliximab therapy. Laboratory findings demonstrated monoclonal IgM-κ paraproteinemia and a high cold agglutinin titer, confirming CAD, while imaging studies and bone marrow evaluation revealed no evidence of overt malignancy. Renal biopsy revealed membranoproliferative glomerulonephritis-like lesions with C3-dominant deposition, consistent with C3 glomerulonephritis (C3GN). These findings suggest that both CAD and C3GN may represent manifestations of OIIA-LPD associated with long-term immunosuppressive therapy. Rituximab combined with glucocorticoids led to a prompt and marked improvement in anemia and renal lesions, resulting in sustained remission of both CAD and C3GN while maintaining RA remission. This case suggests the dual pathogenesis of B-cell dysregulation and complement activation and indicates that B-cell-targeted therapy may contribute to controlling both abnormalities. Accumulation of similar cases will be essential to refine disease classification and to optimize therapeutic strategies for immune-mediated overlap disorders.

Azathioprine (AZA) is widely used during pregnancy to manage autoimmune diseases; however, concerns regarding fetal immunological vulnerability persist. Although neonatal lymphocytopenia and chromosomal abnormalities have been reported following prenatal AZA exposure, little is known about immune recovery in infants after congenital infections in these infants. Here, we describe an infant with congenital cytomegalovirus (CMV) infection, who was born to a mother treated with azathioprine for systemic lupus erythematosus and developed hemophagocytic lymphohistiocytosis (HLH) during immune reconstitution during lymphocytopenia. The preterm infant presented with lymphocytopenia, anemia, thrombocytopenia, and congenital CMV infection. Despite initiating antiviral therapy, immune reconstitution inflammatory syndrome (IRIS) developed, thus fulfilling the diagnostic criteria for HLH, including increased alanine aminotransferase, ferritin, triglycerides, and soluble interleukin-2 receptor levels. A chromosomal analysis revealed mosaicism with 46,XX and i [18](q10) in the bone marrow cells. In the absence of definitive HLH treatment, such as corticosteroids or other immunosuppressive therapies, fever, splenomegaly, and laboratory abnormalities resolved spontaneously, and the chromosomal alterations normalized. This indicates that prenatal AZA exposure induces transient immunosuppression, leading to the development of IRIS. Our case highlights the necessity of vigilant immunological surveillance in neonates exposed to AZA in utero.