Interstitial lung disease (ILD) represents a significant cause of morbidity and mortality in systemic sclerosis (SSc). The purpose of this study was to examine recirculating lymphocytes from SSc patients for potential biomarkers of interstitial lung disease (ILD). Peripheral blood mononuclear cells (PBMCs) were isolated from patients with SSc and healthy controls enrolled in the Vanderbilt University Myositis and Scleroderma Treatment Initiative Center cohort between 9/2017–6/2019. Clinical phenotyping was performed by chart abstraction. Immunophenotyping was performed using both mass cytometry and fluorescence cytometry combined with t-distributed stochastic neighbor embedding analysis and traditional biaxial gating. This study included 34 patients with SSc-ILD, 14 patients without SSc-ILD, and 25 healthy controls. CD21lo/neg cells are significantly increased in SSc-ILD but not in SSc without ILD (15.4 ± 13.3% vs. 5.8 ± 0.9%, p = 0.002) or healthy controls (5.0 ± 0.5%, p < 0.0001). While CD21lo/neg B cells can be identified from a single biaxial gate, tSNE analysis reveals that the biaxial gate is comprised of multiple distinct subsets, all of which are increased in SSc-ILD. CD21lo/neg cells in both healthy controls and SSc-ILD are predominantly tBET positive and do not have intracellular CD21. Immunohistochemistry staining demonstrated that CD21lo/neg B cells diffusely infiltrate the lung parenchyma of an SSc-ILD patient. Additional work is needed to validate this biomarker in larger cohorts and longitudinal studies and to understand the role of these cells in SSc-ILD.
Autoimmune diseases (AID) are increasingly prevalent conditions which comprise more than 100 distinct clinical entities that are responsible for a great disease burden worldwide. The early recognition of these diseases is key for preventing their complications and for tailoring proper management. In most cases, autoantibodies, regardless of their potential pathogenetic role, can be detected in the serum of patients with AID, helping clinicians in making a definitive diagnosis and allowing screening strategies for early -and sometimes pre-clinical- diagnosis. Despite their undoubted crucial role, in a minority of cases, patients with AID may not show any autoantibody, a condition that is referred to as seronegative AID. Suboptimal accuracy of the available laboratory tests, antibody absorption, immunosuppressive therapy, immunodeficiencies, antigen exhaustion, and immunosenescence are the main possible determinants of seronegative AID. Indeed, in seronegative AID, the diagnosis is more challenging and must rely on clinical features and on other available tests, often including histopathological evaluation and radiological diagnostic tests. In this review, we critically dissect, in a narrative fashion, the possible causes of seronegativity, as well as the diagnostic and management implications, in several AID including autoimmune gastritis, celiac disease, autoimmune liver disease, rheumatoid arthritis, autoimmune encephalitis, myasthenia gravis, Sjögren’s syndrome, antiphospholipid syndrome, and autoimmune thyroid diseases. 相似文献
BackgroundSjögren's syndrome (SjS) is a systemic autoimmune disease characterized by lymphocytic infiltration of the salivary and lacrimal glands associated with sicca syndrome. TAFRO syndrome is a systemic inflammatory disease of unknown cause, characterized by Thrombocytopenia, Anasarca, Fever, Reticulin fibrosis, Renal dysfunction and Organomegaly, first reported in 2010 in Japanese patients. Despite their rarity, both conditions have been concurrently reported in several patients during the recent years, hence questioning the existence of shared or related features.MethodsA systematic review of the literature regarding SjS associated with TAFRO syndrome (SjS-TAFRO) was performed. The 2019 updated Masaki diagnostic criteria were used for TAFRO syndrome and SjS was considered when the diagnosis was mentioned by the authors, necessarily with either anti-Sjogren's Syndrome A (SSA) ± anti-Sjogren's Syndrome B (SSB) antibodies and/or histological evidence of focal lymphocytic sialadenitis.ResultsTen cases of SjS-TAFRO have been reported in the literature to date. Compared to SjS patients without TAFRO syndrome, these 10 SjS-TAFRO had a lower female predominance (2.3:1 vs 9:1 women to man ratio) and a higher frequency of anti-SSA antibodies (90% vs 70%). All fulfilled the three major Masaki criteria i.e., anasarca, thrombocytopenia, and systemic inflammation. Seven of them (70%) had megakaryocyte hyperplasia or reticulin fibrosis in the bone marrow. Lymph node biopsy was performed in 8 out of 10 cases (80%) and results were consistent with Castleman disease in 6 (75%). Eight of them had developed renal failure (80%) within six months. Nine of them (90%) had organomegaly, with hepatosplenomegaly in 8 cases and splenomegaly alone in 1.ConclusionThis review brings new insights regarding TAFRO syndrome and suggests it could be a severe manifestation of SjS. The identification of shared abnormal signaling pathways could help in the therapeutic management of both diseases, which face an unmet therapeutic need. 相似文献
Autoantibodies against 3?hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and the signal recognition particle (SRP) are representative antibodies causing immune-mediated necrotizing myopathies (IMNM), called as anti-HMGCR and anti-SRP myopathies, respectively. Here, we analyzed the differences in routine blood test results between 56 anti-HMGCR and 77 anti-SRP myopathy patients. A higher alanine transaminase (ALT) level and a lower aspartate transaminase (AST)/ALT ratio were observed in anti-HMGCR myopathy patients [ALT, 265.7 ± 213.3 U/L (mean ± standard deviation); AST/ALT ratio, 0.88 ± 0.32] than in anti-SRP-myopathy patients (ALT, 179.3 ± 111.2 U/L, p < 0.05; AST/ALT ratio, 1.28 ± 0.40, p < 0.01). In the active phase, anti-HMGCR myopathy often showed ALT predominance, whereas anti-SRP myopathy often showed AST predominance. In addition, there were differences in erythrocyte sedimentation rate (ESR), total cholesterol (TChol) level, and high-density lipoprotein (HDL) level between anti-HMGCR and anti-SRP myopathies (ESR: HMGCR, 24.4 ± 20.8 mm/1 h; SRP, 35.7 ± 26.7 mm/1 h, p = 0.0334; TChol: HMGCR, 226.7 ± 36.6 mg/dL; SRP, 207.6 ± 40.8 mg/dL, p = 0.0163; HDL: HMGCR, 58.4 ± 13.9 mg/dL; SRP, 46.2 ± 17.3 mg/dL, p < 0.01). Additional studies on the differences in routine blood test results may further reveal the pathomechanisms of IMNM. 相似文献
ObjectiveCalcium pyrophosphate crystal deposition disease (CPPD) is a common cause of acute and chronic arthritis, especially in the elderly population. There is a paucity of data regarding the management of CPPD disease, which is currently based on expert opinion and evidence derived from the treatment of gout. We conducted a systematic literature review in order to identify the available treatment options for CPPD, and describe their efficacy and safety.Material and methodsOnline databases were searched from inception to May of 2020 using the search terms: (CPPD [Title/Abstract] OR CPDD [Title/Abstract] OR calcium pyrophosphate [Title/Abstract] OR chondrocalcinosis [Title/Abstract]) AND (treatment [Title/Abstract] OR management [Title/Abstract] OR therapy [Title/Abstract]). Articles evaluating the use of specific treatment agents for CPPD were eligible for inclusion. Case reports were excluded.ResultsA total of 22 eligible studies and 403 unique patients were selected. We identified only 3 randomized, double-blind, controlled trials (RCTs) evaluating the use of methotrexate, hydroxychloroquine, and magnesium carbonate in CPPD, and these therapeutic options, with the exception of methotrexate, have shown efficacy and reduction of pain intensity. Further, 10 case series and 9 cohort studies were included. Intramuscular and intra-articular glucocorticoids, ACTH, as well as the biologic agents anakinra and tocilizumab appear to be efficacious in CPPD. Intra-articular injections of glycosaminoglycan polysulphate, hyaluronic acid and yttrium, as well as synovial membrane destruction by laser irradiation were associated with symptomatic improvement. Due to significant study heterogenicity, direct comparison between studies was not possible.ConclusionThere are a limited number of studies evaluating the treatment of CPPD. High quality evidence is rather limited, while commonly administered agents such as NSAIDs, colchicine and corticosteroids have not been evaluated by RCTs. The need for high quality evidence supporting specific treatment modalities is urgent for this common yet neglected form of arthritis. 相似文献
The COVID-19 pandemic caused by the SARS-CoV-2 virus has significantly disrupted and burdened the diagnostic workup and delivery of care, including transfusion, to cancer patients across the globe. Furthermore, cancer patients suffering from solid tumors or hematologic malignancies were more prone to the infection and had higher morbidity and mortality than the rest of the population. Major signaling pathways have been identified at the intersection of SARS-CoV-2 and cancer cells, often leading to tumor progression or alteration of the tumor response to therapy. The reactivation of oncogenic viruses has also been alluded to in the context and following COVID-19. Paradoxically, certain tumors responded better following the profound infection-induced immune modulation. Unveiling the mechanisms of the virus-tumor cell interactions will lead to a better understanding of the pathophysiology of both cancer progression and virus propagation. It would be challenging to monitor, through the different cancer registries, retrospectively, the response of patients who have been previously exposed to the virus in contrast to those who have not contracted the infection. 相似文献