Immunological Medicine最新文献

Recent evidence indicates an increased risk of chronic kidney disease (CKD) in patients with rheumatoid arthritis (RA), with prevalence rates ranging from 20.8% to 24.5%. Risk factors for CKD among RA patients include advancing age, diabetes, cardiovascular disease, hypertension and RA disease activity. Medications such as glucocorticoids and nonsteroidal anti-inflammatory drugs (NSAIDs) may also accelerate CKD progression. Inflammatory cytokines, notably interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and IL-1, play significant roles in the pathogenesis of both RA and CKD, promoting systemic inflammation and renal impairment. Elevated levels of various cytokines have been detected in the plasma and urine of CKD patients, and they raise morbidity and mortality rates, even during early disease stages. Effective management of RA activity and modifications in treatment to reduce renal burden are essential for lowering CKD risk and improving patient outcomes. Biological disease-modifying antirheumatic drugs (DMARDs), particularly those targeting IL-6 and TNF-α, show potential in mitigating CKD progression in RA patients. However, individualized treatment and careful kidney function monitoring are critical, as CKD may impact RA management. Future research should focus on therapeutic strategies that address inflammation in both RA and CKD to optimize patient care.

We sought to clarify the musculoskeletal ultrasound (MSUS) findings and serum concentrations of cytokines/growth factors in glucocorticoid-resistant polymyalgia rheumatica (GC-R PMR). Patients with PMR admitted to Nagasaki University Hospital (n = 41) were enrolled. MSUS of both shoulder joints was performed in 36 patients. Patients' sera were analyzed for cytokines/growth factors using multiplex assay kits. We examined the cases of 17 males and 24 females (median age 70 years). There were 27 GC-R patients and 14 non-GC-R patients. PD signals were detected in significantly more GC-R patients (65.2%) than non-GC-R patients (23.1%) (p = 0.035). The median serum level of vascular endothelial growth factor (VEGF) was significantly higher in the GC-R group at 871.4 pg/mL than the non-GC-R group (422.8 pg/mL) (p = 0.03) and significantly higher in the PD-positive versus PD-negative patients (p = 0.04). A multivariate analysis revealed that a high serum VEGF level was an independent variable contributing to GC resistance (p = 0.017, odds ratio: 10.34). These results suggest that a high serum VEGF level is a biomarker of GC resistance in PMR, which might be explained by PD-positive neovascularization in inflamed joints of PMR.

Chronic Fatigue Syndrome (CFS) is a complex disorder characterized by prolonged, unexplained fatigue and challenging diagnosis. We report the case of a 35-year-old Japanese woman with CFS who had experienced chronic fatigue since the age of 11 years. Despite treatment with modafinil, methylphenidate, levocarnitine, and ubiquinone, the symptoms persisted. Introduction of oral 5-aminolevulinic acid with sodium ferrous citrate (5-ALA/SFC) led to significant improvements in daily activities, mobility, and psychosocial functioning. Genetic analysis revealed a novel heterozygous frameshift deletion in ADCK1 (p.Asn280fs), a gene related to mitochondrial function, which was confirmed using cDNA sequencing. ADCK1 deficiency has been associated with developmental disabilities, mitochondrial dysfunction, increased reactive oxygen species levels, and apoptosis in Drosophila and muscle cells. This case supports the hypothesis that ADCK1 mutations contribute to mitochondrial dysfunction and CFS pathogenesis. The patient's significant clinical improvement with 5-ALA/SFC and ubiquinone suggests their potential for addressing mitochondrial dysfunction. Further functional and familial analyses are required to confirm the role of this heterozygous ADCK1 mutation in CFS. This case highlights the importance of considering mitochondrial dysfunction in CFS, and the potential therapeutic benefits of 5-ALA/SFC and ubiquinone.

Pyoderma gangrenosum (PG) is an extremely rare disorder in children. We report a nine-month-old girl with PG who presented with high-grade fever and rapidly progressive ulcers at the site of a Bacillus Calmette-Guérin (BCG) inoculation 2 months after the immunization. Additional small pustules developed on her hand and posterior neck three months after the immunization and rapidly progressed. Cytokine profiling demonstrated elevated serum levels of interleukin (IL)-1β, IL-10, IL-17A, IL-6 and IL-18, which is similar to adult cases. Genetic analysis identified heterozygous R202Q variant of the MEFV gene. All of her systemic and local symptoms responded to intravenous methylprednisolone pulse therapy followed by prednisolone 2 mg/kg/day. There is no relapse of PG, to date, even after discontinuation of prednisolone. Atypical skin reactions after a BCG immunization could be an initial manifestation of infantile PG and need attention. Similarity of cytokine profile suggests common pathophysiology of infantile and adult PG.

Aicardi-Goutières syndrome (AGS) and Singleton-Merten syndrome (SMS) are associated with heterozygous gain-of-function mutations in the interferon induced with helicase C domain 1 (IFIH1) gene. Recent reports describe patients exhibiting overlapping clinical features of AGS and SMS, along with marked type I interferon (IFN) overproduction. However, the clinical characteristics and optimal treatment strategies remain unclear. Herein, we present a patient with overlapping clinical features of AGS and SMS who was initially misdiagnosed with juvenile idiopathic arthritis. Surgical soft tissue release of the hip and knee joints improved joint deformities and spastic paraparesis. Baricitinib effectively treated refractory chilblains and skin ulcers while reducing IFN-stimulated gene overexpression in peripheral blood. These findings indicate that baricitinib may be a safe and effective treatment for AGS-SMS overlap, and surgical intervention may be a viable option for refractory joint deformities with spastic paraparesis.

Dry eye disease can be classified as aqueous-deficient, evaporative and mixed-type. Recently, neuropathic pain has been indicated to be involved in the subjective symptoms of aqueous-deficient dry eye. However, the mechanism underlying neuropathic ocular pain in such patients remains elusive. Here, we present the case of a patient with aqueous-deficient dry eye disease and severe corneal and conjunctival epithelial damage due to Sjögren's syndrome. Despite considerable improvements in ocular surface conditions with local treatments, such as punctal plugs, autologous serum eye drops, rebamipide eye drops, and tacrolimus eye drops, the patient experienced severe ocular pain for two years, which was disproportionate to the objective clinical findings. The pain worsened during the exacerbations of systemic symptom, such as arthritis and interstitial pneumonia, without correlating with the ocular surface findings. The administration of mirogabalin, a neuropathic pain medication, effectively alleviated the patient's subjective ocular pain symptoms. Ocular pain in patients with Sjögren's syndrome is not necessarily linked to an aqueous deficiency or ocular surface findings. It can arise as neuropathic ocular pain due to inflammation spreading to the trigeminal nerve. Given the systemic inflammatory condition and characteristics of the ocular pain, administering neuropathic pain medications should be considered as a treatment option.

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.

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.

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.

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.