Rheumatology and immunology research最新文献

Rheumatic diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), are a group of auto-inflammatory disorders associated with substantial morbidity and mortality. One unifying feature of these diseases is the presence of abnormal neutrophils exhibiting dysregulated neutrophil extracellular trap (NET) release, reactive oxygen species (ROS) production, degranulation, and pro-inflammatory cytokines secretion. Moreover, the release of autoantigens associated with NETs promotes the generation of autoantibodies and a breakdown of self-tolerance, thereby perpetuating inflammation and tissue injury in these patients. In recent years, targeted therapies directed at neutrophilic effector functions have shown promising results in the management of rheumatic diseases. In this review, we will highlight the emerging roles of neutrophils in the onset and progression of rheumatic diseases, and further discuss current and future therapeutic approaches targeting the pathogenic functions of neutrophils, which can modulate inflammation and hence improve patients' survival and quality of life.

Primary Sjögren's syndrome (pSS) is an autoimmune systemic disease mainly affecting exocrine glands and resulting in disabling symptoms, as dry eye and dry mouth. Mechanisms underlying pSS pathogenesis are intricate, involving multiplanar and, at the same time, interlinked levels, e.g., genetic predisposition, epigenetic modifications and the dysregulation of both immune system and glandular-resident cellular pathways, mainly salivary gland epithelial cells. Unravelling the biological and molecular complexity of pSS is still a great challenge but much progress has been made in recent years in basic and translational research field, allowing the identification of potential novel targets for therapy development. Despite such promising novelties, however, none therapy has been specifically approved for pSS treatment until now. In recent years, growing evidence has supported the modulation of Janus kinases (JAK) - signal transducers and activators of transcription (STAT) pathways as treatment strategy immune mediated diseases. JAK-STAT pathway plays a crucial role in autoimmunity and systemic inflammation, being involved in signal pathways of many cytokines. This review aims to report the state-of-the-art about the role of JAK-STAT pathway in pSS, with particular focus on available research and clinical data regarding the use of JAK inhibitors in pSS.

Aging-associated immune changes, termed immunosenescence, occur with impaired robust immune responses. This immune response is closely related to a greater risk of development of autoimmune disease (AID), which results in increased levels of autoantibodies and increased morbidity and mortality. In addition, lifestyle-related risk factors play a pivotal role in AID, which may be probable via senescence-related immune cell subsets. Age-associated B cell (ABC) subsets have been observed in those who have rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and multiple sclerosis (MS). Here, this review aims to highlight the mechanisms of ABCs with lifestyle interventions in AID, especially how immunosenescence affects the pathogenesis of AID and the future of aging-associated lifestyle interventions in immunosenescence of AID.

Multicentric reticulohistiocytosis (MRH) is a rare disease of unknown pathogenesis, characterized by skin histiocytosis and destructive arthritis. The present study describes a 53-year-old woman who presented with rheumatoid arthritis (RA) and MRH, which is a clinically rare entity. Diagnosis of MRH was based on nodule pathology. Meanwhile, the patient had typical arthritis, was positive for serum anti-cyclic citrullinated peptide (anti-CCP) antibodies and synovitis confirmed by joint ultrasound, and was diagnosed with RA. Her symptoms resolved with glucocorticoids and methotrexate.

Objectives: Anti-melanoma differentiation-associated gene 5-positive dermatomyositis (MDA5⁺DM) is an autoimmune disease frequently accompanied by rapidly progressive interstitial lung disease (RP-ILD) with high mortality. T cells are implicated in the pathogenesis of MDA5⁺DM and this study aims to measure the frequency and clinical relevance of cytotoxic CD4 and CD8 T cells in this disease.

Methods: T cells expressing Perforin, Granzyme B (GZMB) and Granzyme K (GZMK) were analyzed by flow cytometry from peripheral blood of 19 patients with active MDA5⁺DM and 19 age- and sex-matched healthy donors (HDs). The frequency of CD4 and CD8 T cells and the cytotoxic subsets were compared between patients with MDA5⁺DM and HDs. Correlations within T cell subsets and between T cell subsets and clinical parameters of lactate dehydrogenase (LDH), ferritin, neutrophil-to-lymphocyte ratio (NLR), and Myositis Intention-to-Treat Index (MITAX) were evaluated.

Results: Compared with HDs, patients with active MDA5⁺DM significantly had increased frequency of CD4 T cells, and reduced frequency of GZMK⁺GZMB^- CD8 T cells. Furthermore, the frequency of GZMK⁺GZMB^- CD8 T cells positively correlated with serum ferritin levels in active MDA5⁺DM patients. Notably, the patients in the Dead group of MDA5⁺DM had a significant higher frequency of GZMK⁺GZMB^- CD4 and CD8 T cells.

Conclusion: Substantial changes of cytotoxic T cell subsets are observed in active MDA5⁺DM patients. In addition, a high frequency of GZMK⁺GZMB^- CD4 and CD8 T cells is associated with unfavorable prognosis in MDA5⁺DM. More studies are warranted to further explore the roles of cytotoxic T cells in MDA5⁺DM.

Diagnostic imaging in rheumatology has evolved over the centuries, and novel imaging modalities, including musculoskeletal ultrasonography (MSUS) and magnetic resonance imaging (MRI), are being widely used in the 21st century. With the increase in availability of molecular target-specific therapies, including biologic agents and Janus kinase (JAK) inhibitors, the therapeutic outcome of inflammatory arthritis has changed, and early and accurate diagnosis of inflammatory rheumatic diseases has become more important. Given this situation, MSUS, which is a portable, convenient, noninvasive, and cost-effective imaging technique, plays an important role in the diagnosis of rheumatic diseases. MSUS can be used to detect subclinical inflammation and to accurately determine the distribution of joint involvement and inflammation sites in each joint. Definitive diagnosis for patients with early arthritis should be made after noting their history and performing clinical examination, laboratory testing, and additional procedures. However, MSUS is an extension of physical examination and it can provide a further opportunity and motivation to consider differential diagnoses rather than a conclusive diagnosis. This review aims to describe the usefulness of MSUS in differential diagnoses of the phenotype of early inflammatory arthritis.

Eosinophilic granulomatosis with polyangiitis(EGPA) is a systemic vasculitis syndrome associated with eosinophilia, which most commonly involves the lung, skin, cardiovascular, gastrointestinal, renal, and peripheral nervous systems (PNS). We report a case of a 48-year-old man presented as obstructive jaundice caused by intra-abdominal mass, and he also had elevated peripheral eosinophils. The pathological features of the mass included vasculitis and eosinophils infiltration. At first he was diagnosed as EGPA and treated by glucocorticoid and cyclophosphamide. The patient did not get complete response after six months and then the repeat biopsy proved that he had non-Hodgkin's lymphoma.

Objectives: Systemic sclerosis (SSc) is a heterogeneous complex autoimmune connective tissue disease with variable presentation as a consequence of multisystem involvement. One of the key features of SSc is Raynaud's phenomenon along with vascular endothelial dysfunction that leads to digital ulcers (DUs). Raynaud's tends to be triggered by decreasing thermal gradient exposure, while stress and smoking also play a role. DUs arising as a consequence of severe Raynaud's and vasculopathy are a major cause of morbidity and disability in SSc. We set out to determine the relationship between smoking, Raynaud's phenomenon, DUs, and skin thickness in our Waikato Systemic Sclerosis cohort.

Methods: The Waikato Systemic Sclerosis (SSc) database was used to extract data. Variables collected included demographics, age of diagnosis, SSc subtypes, age at first non-Raynaud's phenomenon, medications used for treatment of Raynaud's phenomenon or ulcers, and maximal modified Rodnan skin score (mRSS). Raynaud's phenomenon and finger DUs (severity for each over the past week and since diagnosis) and a Scleroderma Health Assessment Questionnaire (SHAQ) visual analog 10 cm scale were collected. The lead rheumatologist completed a physician's assessment of Raynaud's and the disease severity questionnaire.

Results: Of the cohort of 143 patients, 100 patients were eligible to complete the questionnaires. Seventy-five patients returned completed questionnaires. Of these, the majority were female (88%), 52 (69.3%) had limited cutaneous systemic sclerosis (lcSSc), 17 (22.7%) had diffuse cutaneous systemic sclerosis (dcSSc), and 6 (8%) had an overlap syndrome. Thirty-six (48%) had a smoking history (in the time frame of collection of serial data). Mean ± standard deviation (SD) pack-years smoked were 17.11 ± 15.29 years. Thirty-five participants had a history of DUs, with a median of 4 DU (range 1-20). Of 17 patients with dcSSc, 12 (70.6%) had ulcers in comparison with 17 of 52 (32.7%) patients with lcSSc. There was a significant relationship between SSc subtype and the number with ulcers (X² = 10.1, P = 0.007). There was also a significant relationship between physician severity of Raynaud's and presence of ulcers (t = 6.1, P < 0.001), which was not evident between patients' severity of Raynaud's and presence of ulcers (t = 1.9, P = 0.06). On the SHAQ score, smokers had significantly worse Raynaud's phenomenon over the prior week (t = 3.08, P = 0.03) and were more likely to note DUs over the preceding week, although the latter was not statistically significant (t = 1.95, P = 0.055). There was no association between smoking and skin thickness as measured by mRSS (r = 0.23, P = 0.19).

Conclusion: Our study demonstrates that smokers have had worse Raynaud's phenomenon over the past week and they