Immunological Medicine最新文献

TAFRO syndrome is a systemic inflammatory disorder of unknown etiology, and its diagnosis requires the exclusion of autoimmune diseases. A 42-year-old Japanese woman presented with TAFRO syndrome-like manifestations, but had undiagnosed limited-cutaneous systemic sclerosis preventing a definitive diagnosis of TAFRO syndrome. However, her clinical course and pathological findings, including renal glomerular microangiopathy, were consistent with TAFRO syndrome. We performed a systematic review of the literature to evaluate how autoimmunity affects the clinical characteristics of TAFRO syndrome/idiopathic multicentric Castleman disease (iMCD)-TAFRO. We reviewed 95 reported cases of TAFRO syndrome/iMCD-TAFRO and found that at least 41 (43.6%) had various autoantibodies. In particular, the positive rates of anti-nuclear antibody, anti-SS-A antibody, anti-SS-B antibody, PA-IgG, and direct Coombs test were high. Furthermore, we identified 14 cases of autoimmune diseases with TAFRO syndrome-like manifestations. We compared the clinical characteristics of these 14 with those of the autoantibody-positive and -negative cases among the 95 cases of TAFRO syndrome/iMCD-TAFRO. Apart from sex ratio, we found no significant difference in clinical presentation, treatment, or outcome among the groups. In conclusion, TAFRO syndrome/iMCD-TAFRO often accompanies autoantibodies and shares many clinical characteristics with other autoimmune diseases. Clinicians should be aware that some autoimmune diseases mimic TAFRO syndrome/iMCD-TAFRO.

T-cell receptor excision circle (TREC)-based newborn screening is a method for the early detection of severe combined immunodeficiency (SCID); however, undetectable TREC level results have also been reported in conditions other than SCID. To date, no studies have investigated the dynamics of TREC levels in patients with Langerhans cell histiocytosis (LCH). Here, we report a case of congenital multisystem LCH with thymic involvement diagnosed following a negative TREC result obtained through newborn screening. Partial remission was achieved with chemotherapy, and TREC levels subsequently recovered. LCH involving the thymus should be considered among the differential diagnoses for negative TREC results.

We report a 29-year-old female with systemic lupus erythematosus (SLE) who promptly developed anxiety after belimumab. She was diagnosed as SLE due to fever, general fatigue, polyarthritis, hypocomplementemia, and positivity of antinuclear antibody and anti-dsDNA antibody, and hydroxychloroquine (HCQ) monotherapy was initiated. Fourteen months following HCQ introduction, arthritis recurred, prednisolone (PSL) 5 mg/day and methotrexate were added. However, since her arthritis recurred during PSL tapering, we added BEL. Three months later, she developed morbid anxiety evaluated by a psychiatrist with protein elevation, interleukin (IL)-6 15.4 pg/mL, anti-neuronal cell antibody (anti-N) 0.66 U/mL (normal <0.27) and autoantibody against anti-N-methyl-D-aspartate receptor subunit GluN2A/B (anti-GluN2) 0.12 U/mL (normal <0.10) in cerebrospinal fluid (CSF). Therefore, we discontinued BEL in consideration of both adverse event in association with BEL as well as neuropsychiatric SLE development. Two months later, her anxiety almost completely disappeared with decreased IL-6 7.0 pg/mL, anti-N 0.36 U/mL and anti-GluN2 0.02 U/mL. As far, no psychiatric manifestation has been developed. Our case indicate that BEL may involve paradoxical elevation of autoantibodies against neurons in the central nervous system, causing neuronal inflammation. Exhaustive investigation of CSF biomarkers could be an important strategy to investigate the pathophysiology of psychiatric manifestations due to BEL.

Neuropsychiatric manifestations in systemic lupus erythematosus (SLE) and anti-phospholipid syndrome (APS) represent complex clinical challenges due to their diverse presentations and multifactorial pathogenesis. Neuropsychiatric SLE (NPSLE) affects approximately 30-40% of SLE patients, with symptoms ranging from cognitive dysfunction to severe conditions such as stroke, seizures, and psychosis. In APS, cerebrovascular events, including ischemic stroke and transient ischemic attacks, occur in ∼20% of patients, alongside non-thrombotic manifestations like migraine and chorea. The underlying mechanisms involve immune-mediated neuronal injury, vascular thrombosis, and neuroinflammation. In NPSLE, autoantibodies, inflammatory cytokines, and complement activation drive neuronal damage, while APS is primarily characterized by antiphospholipid antibody-mediated thrombosis, with additional direct neuronal effects. Advanced neuroimaging, including diffusion tensor imaging, functional MRI, and positron emission tomography, reveals subtle structural and functional brain alterations. Emerging biomarkers, such as neurofilament light chain and glial fibrillary acidic protein, show promise for detecting neural and glial injury. This review synthesizes current insights into the pathophysiology, diagnostic approaches to neuropsychiatric manifestations in SLE and APS, emphasizing the need for integrated clinical, imaging, and laboratory evaluations to improve diagnostic precision and patient outcomes.

This study aimed to investigate the effectiveness and safety of Janus kinase inhibitors (JAKis) in patients with rheumatoid arthritis (RA) in the real world. All consecutive patients with RA from the KEIO-RA cohort who had received a JAKi from July 2013 to June 2023 were included. We assessed drug retention rates, factors associated with retention, disease activity, and adverse events. In total, 294 treatment courses in 201 patients were analyzed. The mean drug continuation duration was 17.2 ± 17.4 months. Full-dose JAKi use and concomitant methotrexate (MTX) use were associated with higher retention rates (p < 0.001 and p = 0.03, respectively). Combination therapy with full-dose JAKi and MTX showed a significantly lower discontinuation rate due to lack of efficacy (p = 0.02), with no increase in safety issues. This pattern was observed across age groups and difficult-to-treat status, though residual confounding cannot be excluded. When comparing retention across five JAKi formulations among patients receiving full-dose JAKi with concomitant MTX, upadacitinib and filgotinib showed significantly lower discontinuation rates due to lack of efficacy (p = 0.04), whereas baricitinib had a lower discontinuation rate due to safety issues (p = 0.01). In conclusion, combination therapy with full-dose JAKi and MTX showed higher retention in this cohort.

This review focuses on the central role of Immunoglobulin E (IgE) in upper respiratory allergic diseases and associated therapeutic strategies. As the core immunoglobulin driving type 2 inflammation, IgE production is meticulously regulated by multiple cytokines and signaling pathways. Current therapeutic approaches primarily involve two strategies: direct inhibition of IgE generation and function, and promotion of Immunoglobulin G4 (IgG4) and Immunoglobulin A (IgA) production to competitively suppress IgE-mediated responses.For direct IgE inhibition, monoclonal antibodies such as omalizumab and dupilumab exert their effects by directly antagonizing IgE or blocking upstream inflammatory cytokines critical for IgE synthesis. A spectrum of other multitarget monoclonal antibodies and non-antibody biologics are also under active investigation. Allergen immunotherapy (AIT) represents the principal approach for enhancing IgG4 and IgA production, aiming to rebalance immune responses through modulation of cytokine profiles, induction of regulatory T cells, and augmentation of allergen-specific IgG4/IgA titres to neutralize allergens and attenuate type 2 inflammation. This article comprehensively dissects the molecular mechanisms underlying IgE biosynthesis, pathological roles in allergic inflammation, and therapeutic intervention strategies, thereby providing novel insights for optimizing treatment protocols and improving clinical outcomes in upper respiratory allergic disorders.

Scleritis is often associated with systemic inflammatory diseases, and a subset of patients remains refractory to conventional therapies, including corticosteroids, immunosuppressants, and tumor necrosis factor inhibitors (TNFi). Janus kinase inhibitors (JAKi) exert anti-inflammatory effects by broadly suppressing downstream cytokine signaling and have been increasingly applied in the management of systemic inflammatory conditions. Recently, more selective JAKi have been developed to minimize adverse effects while preserving therapeutic efficacy. However, clinical experience comparing the efficacy of non-selective versus selective JAKi remains limited. We report a case of highly refractory scleritis positive for proteinase 3-antineutrophil cytoplasmic antibody and suffered from rheumatoid arthritis (RA), and ulcerative colitis (UC). While RA and UC were controlled with TNFi, scleritis remained active and difficult to manage. Following the initiation of tofacitinib, a pan-JAKi, the scleritis rapidly entered remission. However, after tapering and discontinuation of methotrexate and corticosteroids, the scleritis relapsed, suggesting that control was not maintained with tofacitinib and became refractory to treatment. A subsequent switch to upadacitinib, a selective JAK1 inhibitor, resulted in renewed remission and sustained control of ocular inflammation. This case highlights the potential of JAKi as a treatment option for refractory scleritis, particularly in patients unresponsive to conventional therapies, and the possibility of transitioning to a selective JAK1 inhibitor in cases of pan-JAKi resistance.

Myasthenia gravis (MG) is an autoimmune disease affecting the neuromuscular junction, most commonly associated with anti-acetylcholine receptor antibodies, less frequently with muscle-specific kinase antibodies, and occasionally with low-density lipoprotein receptor-related protein 4 antibodies. However, a subset of patients with MG tests negative for all of these three antibodies - termed triple-seronegative MG - posing significant diagnostic and therapeutic challenges. Fast-acting therapies, such as intravenous methylprednisolone (IVMP), intravenous immunoglobulin (IVIG) and plasma exchange (PLEX), are typically recommended during disease exacerbation. However, some patients are refractory to these interventions. For refractory patients with triple-seronegative MG, the efficacy of a recent monoclonal antibody therapy as rescue therapy remains uncertain. We report a case of triple-seronegative MG refractory to repeated IVIG, IVMP and PLEX, in which clinical improvement was achieved following treatment with rozanolixizumab. This case, with long-term follow-up, suggests the potential utility of rozanolixizumab as rescue therapy in a patient subgroup which is typically excluded from randomized controlled trials. Larger studies specifically including patients with triple-seronegative MG are warranted.

Sarcoidosis is a multi-systemic granulomatous disease of unknown etiology. Its association with lymphoproliferative disorders is termed sarcoidosis-lymphoma syndrome, which is typically characterized by sarcoidosis preceding lymphoma. However, the development of sarcoidosis after lymphoma remission is rare. A 72-year-old woman with a history of diffuse large B-cell lymphoma, treated 11 years earlier, was admitted with a rash and weakness in the lower limbs. Multiple inflammatory lesions, predominantly in the lower limbs, were detected using computed tomography and fluorodeoxyglucose positron emission tomography, and a diagnosis of systemic sarcoidosis was established via biopsies of the skin lesion. We reviewed 11 cases of sarcoidosis with cutaneous manifestations after lymphoma treatment, including the present case. In addition, we emphasized the importance of considering cutaneous sarcoidosis in the differential diagnosis of post-treatment skin lesions alongside lymphoma recurrence, as well as the need for histopathological confirmation.

A 68-year-old Japanese woman was diagnosed with palmoplantar pustulosis. She presented with anterior chest pain and swelling, as well as pain in the right first finger. Initially, antibiotics was ineffective, the patient was diagnosed with non-bacterial osteomyelitis. Computed tomography of the chest revealed a sternal bone thickening pattern, and technetium-99m bone scintigraphy showed accumulations in the left sternoclavicular joint and sternal angle. Additionally, contrast-enhanced magnetic resonance imaging revealed osteitis in the sternal scapes and body. Based on these findings, the patient was diagnosed with pustulotic arthro-osteitis. The swelling of the right first finger repeatedly worsened and resolved spontaneously, the first right distal phalanx was amputated to rule out infection and malignancy. Histopathological evaluation revealed evidence of chronic non-bacterial osteitis, and associated with pustulotic arthro-osteitis. We report this case as histopathological examination is rarely performed to confirm the diagnosis of finger osteitis associated with pustulotic arthro-osteitis.