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ID PMID Title PublicationDate abstract
29606669 Flares of Disease in Children with Clinically Inactive Juvenile Idiopathic Arthritis Were 2018 Jun OBJECTIVE: The validity of our current definitions for clinically inactive disease (CID) in juvenile idiopathic arthritis (JIA) based on physical examination is challenged by the development of advanced musculoskeletal imaging tools. We aimed to prospectively determine the prevalence of abnormal ultrasound (US) findings in children with CID in JIA and their clinical significance. METHODS: Children aged ≥ 4 years with CID and a history of arthritis from a single tertiary center were approached over 1 year. Standard US of knees, tibiotalar joints, subtalar joints, and wrists were performed at baseline and at a followup visit. US images were scored by 2 pediatric musculoskeletal radiologists. RESULTS: Forty children with CID were enrolled and followed clinically. The median duration of inactive disease was 1 year. The most common International League of Associations for Rheumatology JIA categories were extended oligoarticular JIA (30%) and rheumatoid factor-negative polyarthritis (38%). At baseline, among a total of 289 joints scanned, 24 joints (8%) had at least 1 abnormal finding in 18 (45%) of 40 subjects. When evaluated at the individual joint level against flares identified during followup exams, these baseline US findings had a sensitivity of 15% and a positive predictive value of 12%. The predictive performance of the second US was even less. CONCLUSION: Our study demonstrates that nearly half of children with CID had abnormal US findings in 1 of 8 commonly affected joints. These findings did not correlate with subsequent clinical flares in up to 2 years of followup.
29361207 The Ratio of Blood T Follicular Regulatory Cells to T Follicular Helper Cells Marks Ectopi 2018 May OBJECTIVE: To investigate whether the balance of blood follicular helper T (Tfh) cells and T follicular regulatory (Tfr) cells can provide information about ectopic lymphoid neogenesis and disease activity in primary Sjögren's syndrome (SS). METHODS: We prospectively recruited 56 patients clinically suspected of having SS. Sixteen of these patients subsequently fulfilled the American-European Consensus Group criteria for SS and were compared to 16 patients with non-SS sicca syndrome. Paired blood and minor salivary gland (MSG) biopsy samples were analyzed to study Tfr cells and subsets of Tfh cells in both compartments. RESULTS: Patients with primary SS had normal Tfh cell counts in peripheral blood; however, activated programmed death 1-positive (PD-1+) inducible costimulator-positive (ICOS+) Tfh cells in peripheral blood were strongly associated with disease activity assessed by the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (r = 0.8547, P = 0.0008). Conversely, the blood Tfr cell:Tfh cell ratio indicated ectopic lymphoid structure formation in MSGs, being strongly associated with B cell, CD4+ T cell, and PD-1+ICOS+ T cell infiltration in MSGs, and was especially increased in patients with focal sialadenitis. Further analysis showed that the blood Tfr cell:Tfh cell ratio allowed discrimination between SS patients and healthy donors with excellent accuracy and was a strong predictor of SS diagnosis (odds ratio [OR] 12.96, P = 0.028) and the presence of focal sialadenitis (OR 10, P = 0.022) in patients investigated for sicca symptoms, thus highlighting the potential clinical value of this marker. CONCLUSION: The blood Tfr cell:Tfh cell ratio and PD-1+ICOS+ Tfh cells constitute potential novel biomarkers for different features of primary SS. While the blood Tfr cell:Tfh cell ratio is associated with ectopic lymphoid neogenesis, activated Tfh cells indicate disease activity.
29130113 Long-term results of closed reduction for developmental dislocation of the hip in children 2018 Jan BACKGROUND: Developmental dysplasia of the hip (DDH) diagnosed in older postnatal children can be effectively treated by closed reduction (CR) alone. However, no prospective or comparative trial to explore the differential effectiveness of CR between non-walking and walking postnatal children has yet been reported. This study investigated the clinical and radiologic outcomes of CR in the age range of interest (12-18 months old) via a prospective trial and compared these results with those of a younger age group who also underwent CR. PATIENTS AND METHODS: Between 1999 and 2009, 56 children diagnosed with DDH were enrolled. Of these, 45 were followed after CR for a period of at least seven years. The anatomical parameters of the hip/pelvis, including arthrograms, were evaluated and compared before and after CR. The final radiologic status, including the occurrence of avascular necrosis (AVN), and clinical outcomes were evaluated and compared. RESULTS: The mean ages at the start of treatment were 6.11 and 15.29 months old in group 1 and group 2, respectively. None of the children required surgical open reduction during the follow-up period. The final status of hips were classified according to the Bucholz-Ogden system. Two type II hips and one type I hip were found in group 1. In group 2, two type I hips and one type III hip were observed at the final follow-up. The overall clinical outcomes were satisfactory in both groups, according to McKay's criteria. No significant differences in clinical outcomes between the two groups were found (P = 0.382). Surgery was performed for just one patient in group 2 at seven years old. CONCLUSIONS: CR in DDH for postnatal children 12-18 months old may provide similar results to the non-walking age group if performed with preliminary traction, gentle CR under general anaesthesia, percutaneous adductor tenotomy, and the minimization of forceful abduction.
29749720 Brief Report: Anti-Calponin 3 Autoantibodies: A Newly Identified Specificity in Patients W 2018 Oct OBJECTIVE: Autoantibodies are clinically useful for phenotyping patients across the spectrum of autoimmune rheumatic diseases. Using serum from a patient with Sjögren's syndrome (SS), we detected a new specificity by immunoblotting. This study was undertaken to identify this autoantibody and to evaluate its disease specificity. METHODS: A prominent 40-kd band was detected when immunoblotting was performed using SS patient serum and lysate from rat dorsal root ganglia (DRGs). Using 2-dimensional gel electrophoresis and liquid chromatography tandem mass spectrometry peptide sequencing, the autoantigen was identified as calponin 3. Anti-calponin 3 antibodies were evaluated in sera from patients with primary SS (n = 209), patients with systemic lupus erythematosus (SLE; n = 138), patients with myositis (n = 138), patients with multiple sclerosis (MS; n = 44), and healthy controls (n = 46) by enzyme-linked immunosorbent assay. Expression of calponin 3 was assessed by immunohistochemistry. RESULTS: Calponin 3 was identified as a new autoantigen. Anti-calponin 3 antibodies were detected in 23 (11.0%) of the 209 SS patients, 12 (8.7%) of the 138 SLE patients, 7 (5.1%) of the 138 myositis patients, 3 (6.8%) of the 44 MS patients, and 1 (2.2%) of the 46 healthy controls. Among SS patients, the frequency of anti-calponin 3 antibodies was highest in those with neuropathies (7 [17.9%] of 39). In this subset, the frequency of anti-calponin 3 antibodies differed significantly from that in the control group (P = 0.02). Calponin 3 was expressed primarily in rat DRG perineuronal satellite cells but not neurons. CONCLUSION: Calponin 3 is a novel autoantigen. Antibodies against this protein are found in SS and associate with the subset of patients experiencing neuropathies. Intriguingly, we found that calponin 3 is expressed in DRG perineuronal satellite cells, suggesting that these may be a target in SS.
29074164 Defective regulation of L1 endogenous retroelements in primary Sjogren's syndrome and syst 2018 Mar OBJECTIVE: To investigate whether altered DNA methylation contributes to the inappropriate expression of LINE-1 (L1) retroelements in primary Sjogren's syndrome (SS) and systemic lupus erythematosus (SLE). METHODS: Minor salivary glands (MSG) were obtained from 42 patients with primary SS [23 without adverse predictors for lymphoma development (SS-low risk), 7 SS-high risk and 12 complicated by B-cell lymphoma (SS-lymphoma)] and 17 sicca controls (SC). Additionally, kidney biopsy specimens and PBMCs were obtained from 23 and 73 lupus patients, respectively. Relative mRNA expression was quantified for full-length L1 transcripts, along with mediators of methylation. In an independent set of 44 MSG samples (11 SS-low risk, 10 SS-high risk, 15 SS-lymphoma and 8 SC), methylation levels of the L1 promoter were determined by bisulphite pyrosequencing. RESULTS: A strong positive correlation was demonstrated between L1 transcripts and gene products that mediate de novo and constitutive DNA methylation, DNA methyltransferase (DNMT)3B, DNMT1, and methyl CpG binding protein 2 (MeCP2), in both SS MSG and lupus renal tissues. A significant negative correlation was observed between expression of L1 and lymphoid-specific helicase (LSH, encoded by HELLS) in both SS MSG and SLE kidney tissues, as well as between DNMT3A transcripts and L1 expression in SLE kidney tissues and PBMCs. Reduced levels of L1 promoter methylation along with increased DNMT3B, DNMT1, and MeCP2, but reduced LSH levels were detected in SS-low risk patients compared to both SS-lymphoma and SC. The SS-lymphoma group was also characterized by a profound decrease of MeCP2 and DNMT3B compared to SC. CONCLUSION: Our data support a contributory role of altered methylation mechanisms in the pathogenesis of systemic autoimmune disorders and related lymphoproliferative processes and suggest that LSH and DNMT3A should be investigated as candidate upstream mediators of decreased L1 promoter methylation and increased L1 expression.
30178506 The Sjögren's syndrome-associated autoantigen Ro52/TRIM21 modulates follicular B cell hom 2018 Dec Systemic rheumatic diseases are characterized by abnormal B cell activation with autoantibody production and hypergammaglobulinaemia. Ro52/SSA, also denoted tripartite motif (TRIM)21, is a major autoantigen in Sjögren's syndrome and systemic lupus erythematosus. Interestingly, TRIM21-deficient mice develop systemic autoimmunity with B cell-driven manifestations such as autoantibodies, hypergammaglobulinaemia and glomerulonephritis following tissue injury. The mechanisms by which TRIM21-deficiency leads to enhanced B cell activation and antibody production are, however, not well understood, and to further elucidate the role of TRIM21 in systemic autoimmunity, we investigated the B cell phenotype and antibody responses of Trim21(-/-) mice following immunization with thymus-dependent (TD) and thymus-independent (TI) antigens. We found that TRIM21-deficient mice developed significantly higher specific antibody titres than their wild-type counterparts upon B cell receptor (BCR) engagement by TD and TI type II antigens, and this was accompanied by an altered B cell phenotype. Furthermore, BCR cross-linking, but not anti-CD40 stimulation, in vitro resulted in a significantly higher proliferation of Trim21(-/-) cells. We also observed that splenic follicular B cells were expanded not only in immunized mice but also already in young, unmanipulated Trim21(-/-) mice, and transcriptomic analysis of these cells revealed an up-regulation of genes associated with B cell differentiation, indicating a role for TRIM21 in their regulation. In conclusion, in this study we describe a link between the rheumatic autoantigen Ro52/TRIM21 and increased antibody production associated with follicular B cell expansion, implicating a potential role for Ro52/TRIM21 in the pathogenesis of systemic autoimmune diseases.
29867966 Autoantibodies Recognizing Secondary NEcrotic Cells Promote Neutrophilic Phagocytosis and 2018 Deficient clearance of apoptotic cells reportedly contributes to the etiopathogenesis of the autoimmune disease systemic lupus erythematosus (SLE). Based on this knowledge, we developed a highly specific and sensitive test for the detection of SLE autoantibodies (AAb) utilizing secondary NEcrotic cell (SNEC)-derived material as a substrate. The goal of the present study was to validate the use of SNEC as an appropriate antigen for the diagnosis of SLE in large cohort of patients. We confirmed the presence of apoptotically modified autoantigens on SNEC (dsDNA, high mobility group box 1 protein, apoptosis-associated chromatin modifications, e.g., histones H3-K27-me3; H2A/H4 AcK8,12,16; and H2B-AcK12). Anti-SNEC AAb were measured in the serum of 155 patients with SLE, 89 normal healthy donors (NHD), and 169 patients with other autoimmune connective tissue diseases employing SNEC-based indirect enzyme-linked immunosorbent assay (SNEC ELISA). We compared the test performance of SNEC ELISA with the routine diagnostic tests dsDNA Farr radioimmunoassay (RIA) and nucleosome-based ELISA (anti-dsDNA-NcX-ELISA). SNEC ELISA distinguished patients with SLE with a specificity of 98.9% and a sensitivity of 70.6% from NHD clearly surpassing RIA and anti-dsDNA-NcX-ELISA. In contrast to the other tests, SNEC ELISA significantly discriminated patients with SLE from patients with rheumatoid arthritis, primary anti-phospholipid syndrome, spondyloarthropathy, psoriatic arthritis, and systemic sclerosis. A positive test result in SNEC ELISA significantly correlated with serological variables and reflected the uptake of opsonized SNEC by neutrophils. This stresses the relevance of SNECs in the pathogenesis of SLE. We conclude that SNEC ELISA allows for the sensitive detection of pathologically relevant AAb, enabling its diagnostic usage. A positive SNEC test reflects the opsonization of cell remnants by AAb, the neutrophil recruitment to tissues, and the enhancement of local and systemic inflammatory responses.
29654981 Urinary metabolomics study on the anti-inflammation effects of flavonoids obtained from Gl 2018 Jun 1 Rheumatoid arthritis (RA) is a chronic disease with pain, swelling, and limitation in the motion and function of multiple joints thus leading to high disability. Previous studies have shown that flavonoids and saponins are the most abundant and active constituents in Glycyrrhiza, which possess a wide range of pharmacological effects such as anti-inflammatory, antioxidant and anti-bacteria. But the mechanisms of those actions are not entirely clear. In order to clarify the mechanisms of those actions, the pharmacodynamical assessments of extraction of water-soluble components and flavonoids and saponins obtained from Glycyrrhiza were investigated. Combining the pharmacodynamical researches, we found that flavonoids obtained from Glycyrrhiza had more significant therapeutic effects on acute inflammation, chronic inflammation and inflammatory pain than that of extraction of water-soluble components and saponins obtained from Glycyrrhiza. The results indicated that flavonoids are the main medicinal ingredients in Glycyrrhiza. In order to further investigate the mechanism of the action of flavonoids in Glycyrrhiza on treating RA, a urine metabolomics method based on ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was established to observe the metabolic variations in adjuvant-induced arthritis (AIA) rats and investigate the therapeutic effect of flavonoids in Glycyrrhiza on RA. As a result, twenty potential biomarkers were found by comparison with the model group (MG) and flavonoid treated group (FG). We associated these compounds with related metabolic pathways, the results showed that these biomarkers were mainly associated with purine metabolism, taurine and hypotaurine metabolism, tryptophan metabolism, phenylalanine metabolism, tricarboxylic acid cycle (TCA cycle), pantothenate and coenzyme A (CoA) biosynthesis. The results about the pharmacodynamics and metabolomics provided a theoretical basis for clarifying the mechanism of flavonoids in Glycyrrhiza in the treatment of RA.
29619588 Autoimmune/inflammatory syndrome induced by mineral oil: a health problem. 2018 Jun Autoimmune/inflammatory syndrome induced by adjuvant (ASIA) includes the following conditions: siliconosis, Gulf War syndrome, macrophagic myofasciitis syndrome, and post-vaccination phenomena. Afterward, other syndromes have been recognized, such as in ASIA by mineral oil (ASIA-MO). These conditions are triggered by adjuvants and they are the result of the interplay of genetic and environmental factors. ASIA-MO is defined as the infiltration of oily type modeling substances for cosmetic purposes. It has been reported in many countries and used surreptitiously. Pathogenesis of ASIA-MO is not clear, but is characterized by chronic granulomatous inflammation, like the pristane model in mice, with increase of proinflammatory cytokines: type I interferons (IFNα and IFNß), systemic lupus erythematosus (SLE), and erosive arthritis. In humans, an increase of interleukin 1 (IL-1) has been found. Clinical spectrum of ASIA-MO is heterogeneous, varying from mild to severe and being local and systemic. The systemic manifestations can be non-specific and specific, meeting criteria for any autoimmune disease (AID), i.e., SLE, rheumatoid arthritis, and systemic sclerosis, among others. The areas of the body where the mineral oil is mostly applied include the following: buttocks (38-72%), breasts (12-16%), lower extremities (18-22%), and face (6-10%). The penis augmentation is also common. Treatment is focused on local and systemic manifestations and requires medical and surgical management representing a challenge for the physician.
29661540 MIF functional polymorphisms (-794 CATT(5-8) and -173 G>C) are associated with MIF serum l 2018 Jul 15 Macrophage migration inhibitory factor (MIF) is a cytokine associated with tissue damage in multiple autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis and psoriatic arthritis. The role of MIF in multiple sclerosis (MS) and the contribution of its polymorphisms are unknown in our population. Therefore, we decided to investigate the genetic association of -794 CATT(5-8) (rs5844572) and -173 G>C (rs755622) MIF polymorphisms with MS, clinical variables and MIF serum levels in the population of western Mexico. 230 MS patients diagnosed according to McDonald criteria and 248 control subjects (CS) were recruited for this study, both polymorphisms were genotyped by PCR and PCR-RFLP and MIF serum levels were measured by ELISA kit. Severity and progression of MS were evaluated by EDSS and MSSS scores, respectively. Genotypes carrying the 5 repeats alleles of -794 CATT(5-8)MIF polymorphism present higher MIF serum levels in comparison with no carriers, and the presence of 5,7 heterozygous genotype contribute to the increase of disease severity and damage progression in MS patients. Notably when we stratified by sex, an effect of risk alleles (7 repeats and -173*C) of both MIF polymorphisms on EDSS and MSSS scores on males was found (p < 0.01). This study suggests that polymorphic alleles of MIF polymorphisms could act as sex-specific disease modifiers that increase the severity and progression of MS in male Mexican-Mestizo western population.
28812405 Simple screening tools predict death and cardiovascular events in patients with rheumatic 2018 Mar OBJECTIVES: Patients with rheumatic disease (RD) have an increased mortality risk compared with the general population, mainly due to cardiovascular disease (CVD). We aimed to identify patients at high risk of CVD and mortality by comparing three screening tools suitable for clinical practice. METHOD: In this prospective, single-centre study, consecutive patients with rheumatoid arthritis (RA), systemic autoimmune disease (SAI), or spondyloarthritides (SpA) including psoriatic arthritis underwent a comprehensive cardiovascular risk assessment. Patients were predefined as being at high risk for cardiovascular events or death if any of the following were present: European Systematic COronary Risk Evaluation (SCORE) ≥ 3%, N-terminal pro-brain natriuretic peptide (NT-proBNP) ≥ 200 pg/mL, or any pathological electrocardiogram pattern. RESULTS: The patient population (n = 764) comprised 352 patients with RA, 260 with SAI, and 152 with SpA. After a median follow-up of 5.2 years, 6.0% of RD patients had died (7.0%, 7.2%, and 1.4% of patients in the RA, SAI, and SpA subgroups), and 5.0% had experienced a cardiovascular event (5.0%, 6.4%, and 2.8%, respectively). For all RD patients and the RA and SAI subgroups, NT-proBNP ≥ 200 pg/mL and SCORE ≥ 3% identified patients with a 3.5-5-fold increased risk of all-cause death and cardiovascular events. Electrocardiogram pathology was associated with increased mortality risk, but not with cardiovascular events. CONCLUSION: NT-proBNP ≥ 200 pg/mL or SCORE ≥ 3% identifies RA and SAI patients with increased risk of cardiovascular events and death. Both tools are suitable as easy screening tools in daily practice to identify patients at risk for further diagnostics and closer long-term follow-up.
31338169 Tolerance and safety of rapid 2-hour infusion of rituximab in patients with kidney-affecti 2019 Jul OBJECTIVE: According to the manufacturer's documentation, rituximab (RTX) should be administered with slow infusion rates to prevent infusion-related adverse events (AEs). Nevertheless, slow infusions are time-consuming and uncomfortable for patients and medical staff. Therefore, faster infusion rates have been studied and proven safe and well tolerated in lymphomas and rheumatoid arthritis (RA). A small amount of data is available for rapid RTX infusions in non-RA autoimmune diseases. METHODS: Beginning in September 2015, all RTX-reated patients in our centre and willing to participate, were switched from slow RTX infusions (4.25 hours, given at least once to all patients) to fast infusions (2 hours). A total of 85 RTX 2-hour infusions was administered to 53 patients with autoimmune diseases with renal involvement and selected primary glomerulonephritides (26 ANCA-associated vasculitis, nine systemic lupus erythematodes, seven membranous nephropathy, five IgM nephropathy and six other autoimmune disease). Most of the patients received chronic corticosteroid therapy. The prednisone equivalent dose median (IQR) was 0.1 (0.0-0.2) mg/kg/day. RESULTS: Rapid RTX infusions were generally well tolerated. Only two infusion-related AEs were recorded: one Common Terminology Criteria for Adverse Events, grade 3, (lower back pain and hypotension followed by chills necessitating methylprednisolone and dipyrone administration) and one grade 1 (subjective intolerance). The AEs frequency does not differ from other studies with rapid RTX infusions in patients with lymphomas and RA. CONCLUSIONS: Our experience supported other published data and provides evidence concerning the safety of non-initial RTX 2-hour infusion which can be administered without raising the infusion-related AEs rate in patients with kidney-affecting autoimmune diseases and glomerulonephritides.
30627464 Posterior Reversible Encephalopathy Syndrome with Stroke in Puerperal Woman with High Tite 2018 Posterior reversible encephalopathy syndrome with stroke is very rare in puerperal women. A 36-year-old nulliparous woman with both rheumatoid arthritis and recurrent pregnancy loss, probably due to a high titer of anti-phospholipid IgM antibody, was referred at 10 weeks of gestation. Low-dose aspirin at 100 mg/day and heparin calcium subcutaneous injection at 10,000 units/day were started before pregnancy and stopped at 35(+6) and 40(+2) weeks, respectively. She transabdominally delivered a male infant weighing 3,344 g at 40(+5) weeks. A tonic-clonic seizure abruptly occurred without either hypertension or proteinuria 5 days after delivery. Intracerebral hemorrhage involving an area of 2 cm in diameter in the right frontal lobe and subarachnoid hemorrhage with PRES were confirmed. Seizure recurred 2 days after the initial episode. She showed severe headache and mild disturbance of consciousness but no neurological findings. We suggested that a high titer of anti-phospholipid IgM antibody might be associated with stroke.
30568073 Risk of Delayed Healing of Tooth Extraction Wounds and Osteonecrosis of the Jaw among Pati 2018 Dec Bone-modifying or antiresorptive agents that target osteoclasts, such as bisphosphonates, are known to cause delayed wound healing and osteonecrosis of the jaw (ONJ) following tooth extraction. However, there are no data on whether such adverse events are also caused by drugs that may suppress the immune system, including corticosteroids, immunosuppressants, biological agents, and disease-modifying anti-rheumatic drugs (DMARDs). The aim of this retrospective study was to examine the incidence of delayed post-extraction wound healing and identify risk factors among patients treated with potential immunosuppressive drugs undergoing tooth extraction. We performed a retrospective cohort study involving 101 patients by reviewing their medical records. The underlying diseases of the enrolled patients included dilated cardiomyopathy, hematological malignancy, sarcoidosis, rheumatoid arthritis, and systemic lupus erythematosus. The sample comprised 131 cases of tooth extraction among the 101 patients; delayed post-extraction wound healing occurred in 10 patients (12 cases, 9.2%), including ONJ in three patients (3 cases, 2.3%). The surgical tooth extraction performed for impacted teeth or a residual root (P = 0.009), the number of surgical tooth extraction (P = 0.012), decreased lymphocyte counts (P = 0.008), and decreased eosinophil counts (P = 0.009) were significantly related to delayed wound healing. Thus, among patients taking corticosteroids, immunosuppressants, biological agents, and/or DMARDs, there is a risk of delayed wound healing and ONJ. Moreover, the significant risk factors are low lymphocyte counts, low eosinophil counts, and surgical extraction. It is of particular importance to prevent surgical site infection, when the high-risk patients undergo tooth extraction.
30544444 Increased nerve twigs in small intestinal mucosa with programmed cell death-ligand 1 and s 2018 Dec RATIONALE: Inflammatory bowel disease (IBD) patients manifest symptoms of disturbed gut function, such as neural sensory-motor changes. Programmed cell death-ligand 1 (PD-L1), normally present in neural tissue, exists in close apposition to the mucosal immune system and intestinal epithelium, and a bi-directional communication is known to occur at these interfaces. Somatostatin has been shown to suppress the inflammatory reaction, and has been used in several clinical trials to treat inflammatory disorders, such rheumatoid arthritis. Recently, somatostatin receptor type 2A, that regulates neurotransmission, proliferation, and apoptosis, has been recognized in IBD. Although prominent abnormalities in the morphology of the enteric nervous system have been observed in idiopathic IBD, they are more marked in Crohn disease. PATIENT CONCERNS: A 55-year-old woman with recurrent Crohn disease, just surgically treated for ileal resection, have a stenotic complication. INTERVENTIONS: At surgery 5 cm of preterminal ileum with stenosis and anastomotic ileocolic block was removed. DIAGNOSES: The histopathology showed a recurrent Crohn in fistulo-stenotic phase; the stenosis was mainly sustained by mass-forming, ganglioneuromatous hyperplasia. Normally very rare, fine nerve twigs extend up into mucosa but we found a new-formed fibrillary network, extending into the inflammation area at the subepithelial luminal site of the mucosa, that was positive to PD-L1 and somatostatin receptor type 2A (SSTR2A) immunostaining but not visualized in routinary stained slides. OUTCOMES: After surgery the patient was semestrally followed with clinical endoscopic evaluation that results uneventfully. LESSONS: Our case shows that before surgery neuromatous abnormalities can be predicted by immunostained new-formed twigs in the mucosa.
30542457 Bioinformatics analysis reveals different gene expression patterns in the annulus fibrosis 2018 Dec Degeneration of the intervertebral disc (IVD), which consists of the annulus fibrosus (AF) and nucleus pulposus (NP), is a multifactorial physiological process associated with lower back pain. Despite decades of research, the knowledge of the underlying molecular mechanisms of IVD degeneration (IDD) has remained limited. The present study aimed to reveal the differential gene expression patterns in AF and NP during the process of IDD and to identify key biomarkers contributing to these differences. The microarray dataset GSE70362 containing 24 AF and 24 NP samples was retrieved from the Gene Expression Omnibus database. Of these, 8 healthy samples were discarded. GeneSpring11.5 software was employed to identify differentially expressed genes (DEGs). Metascape online tools were used to perform enrichment analyses. Finally, the DEGs were mapped with the Search Tool for the Retrieval of Interacting Genes, and a protein-protein interaction (PPI) network was constructed in Cytoscape software. A total of 87 DEGs were identified. Gene ontology enrichment revealed that these DEGs were mainly involved in the inflammatory response, the extracellular matrix and RNA polymerase II transcription factor activity. Pathway enrichment revealed that the DEGs were mainly involved in the transforming growth factor (TGF-β) and estrogen signaling pathways. Matrix metalloproteinase (MMP)1 and interleukin (IL)6 were included in the genes enriched in rheumatoid arthritis, whereas bone morphogenetic protein (BMP)2 and thrombospondin 1 (THBS1) were among the genes enriched in the TGF-β signaling pathway. In the PPI network, IL6 was identified as the central gene. In conclusion, as MMP1 has been demonstrated degrade collagen III at higher rates compared with other types of collagen (which is at a higher quantity in AF than NP), collagen types may be in different distribution patterns, which may contribute to the upregulation of MMP1 in AF. Differences in the expression of BMP2, ESR1 and THBS1 may explain for the pathological differences between AF and NP. IL6 may have a key role in different degeneration processes in AF and NP.
30505501 Interstitial lung disease associated with anti-citrullinated peptide/protein antibody-posi 2018 Oct Little has been reported on the characteristics of interstitial lung disease (ILD) associated with anti-citrullinated peptide/protein antibody (ACPA)-positive anti-synthetase syndrome (ASS). We sought to investigate the clinical, radiologic, and pathologic features of patients with ILD associated with ACPA-positive ASS. Medical records of seven ILD patients with positive results of both ACPA and anti-aminoacyl-tRNA synthetase antibody were retrospectively reviewed. Five patients had clinical symptoms associated with ASS other than ILD. On high-resolution computed tomography (HRCT) analysis, a nonspecific interstitial pneumonia (NSIP) pattern was shown in 3 patients and NSIP with organizing pneumonia (OP) overlap in 2 patients. Coronal slices of these 5 patients showed lower lung disease predominance with traction caudally on major fissures due to lower lobe volume loss. These were features that could commonly be observed in ASS-associated ILD. Pathological findings available for 3 patients showed NSIP. The characteristics of ILD associated with ACPA-positive ASS appear to be similar to those of ILD associated with ASS, but not to rheumatoid arthritis (RA) or ACPA, especially in terms of the radiological findings.
30459597 Anakinra Therapy for Non-cancer Inflammatory Diseases. 2018 Interleukin-1 (IL-1) is the prototypical inflammatory cytokine: two distinct ligands (IL-1α and IL-1β) bind the IL-1 type 1 receptor (IL-1R1) and induce a myriad of secondary inflammatory mediators, including prostaglandins, cytokines, and chemokines. IL-1α is constitutively present in endothelial and epithelial cells, whereas IL-1β is inducible in myeloid cells and released following cleavage by caspase-1. Over the past 30 years, IL-1-mediated inflammation has been established in a broad spectrum of diseases, ranging from rare autoinflammatory diseases to common conditions such as gout and rheumatoid arthritis (RA), type 2 diabetes, atherosclerosis, and acute myocardial infarction. Blocking IL-1 entered the clinical arena with anakinra, the recombinant form of the naturally occurring IL-1 receptor antagonist (IL-1Ra); IL-1Ra prevents the binding of IL-1α as well as IL-1β to IL-1R1. Quenching IL-1-mediated inflammation prevents the detrimental consequences of tissue damage and organ dysfunction. Although anakinra is presently approved for the treatment of RA and cryopyrin-associated periodic syndromes, off-label use of anakinra far exceeds its approved indications. Dosing of 100 mg of anakinra subcutaneously provides clinically evident benefits within days and for some diseases, anakinra has been used daily for over 12 years. Compared to other biologics, anakinra has an unparalleled record of safety: opportunistic infections, particularly Mycobacterium tuberculosis, are rare even in populations at risk for reactivation of latent infections. Because of this excellent safety profile and relative short duration of action, anakinra can also be used as a diagnostic tool for undefined diseases mediated by IL-1. Although anakinra is presently in clinical trials to treat cancer, this review focuses on anakinra treatment of acute as well as chronic inflammatory diseases.
30290642 A case report of Legionella and Mycoplasma pneumonia: Co-incidence or co-infection? 2018 Oct RATIONALE: Concurrent or sequential coinfections of Legionella pneumophila and Mycoplasma pneumoniae have been reported in the past though infrequently. Distinguishing a true co-infection from cross reactivity is often challenging as the diagnosis is mostly dependent on serological testing. PATIENT CONCERNS: A 77-year-old male presented with worsening dyspnea, cough with yellow sputum, diarrhea and fever of 2-days duration. Patient had history of chronic obstructive pulmonary disease (COPD) on home oxygen, bronchiectasis, rheumatoid arthritis (on methotrexate and leflunomide), treated pulmonary tuberculosis and 30-pack-year smoking. Chest X-ray showed bilateral interstitial changes with left lower lobe infiltrate. On day 5, his urine antigen for L pneumophila serogroup 1 was reported positive. The following day his serum M pneumoniae IgM antibody titers were reported elevated at 6647 U/mL. Patient was started on antibiotics and placed on non-invasive positive pressure ventilation. DIAGNOSIS: The patient was diagnosed with possible Legionella and Mycoplasma co-infection. OUTCOMES: Sputum Mycoplasma polymerase chain reaction (PCR) and serum cold agglutinins were obtained on day 6 and later reported negative. He was treated with azithromycin for 10 days with clinical improvement. LESSONS: Serological testing alone is an indirect measure with poor sensitivity and specificity and has its own limitations. Urine antigen detection confirms L pneumophila serogroup 1 infection in a patient with suggestive symptoms. However, diagnosis of M pneumonia should be based on combination of tests including serology and PCR to confirm true co-infection.
30028258 Factors associated with development and mortality of pulmonary hypertension in systemic lu 2018 Oct Objectives This study aims to identify the factors associated with the development and mortality of pulmonary hypertension (PH) in systemic lupus erythematosus (SLE) patients. Methods We conducted a prospective study of SLE patients in a single tertiary center. PH was defined as a systolic pulmonary arterial pressure ≥30 mmHg on transthoracic echocardiography. We assessed potential associated factors contributing to the development and mortality of PH in SLE patients. Results Of 1110 patients with SLE, 48 patients were identified to have PH. Multivariable analysis indicated that pleuritis or pericarditis (odds ratio (OR) = 4.62), anti-RNP antibody (OR = 2.42), interstitial lung disease (ILD) (OR = 8.34) and cerebro-cardiovascular disease (OR = 13.37) were independently associated with the development of PH in SLE. Subgroup analysis among patients with PH demonstrated that there were no statistically significant factors associated with PH mortality in SLE. Conclusions The prevalence of PH was 4.3% in our cohort. There were significant associations with pleuritis or pericarditis, anti-RNP antibody, ILD, and cerebro-cardiovascular disease in SLE, which may contribute to the development of PH. However, there were no statistically significant factors associated with PH mortality in SLE.