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ID PMID Title PublicationDate abstract
32864787 Resolving the Interactome of the Human Macrophage Immunometabolism Regulator (MACIR) with 2020 Oct Expression of the macrophage immunometabolism regulator gene (MACIR) is associated with severity of autoimmune disease pathology and with the regulation of macrophage biology through unknown mechanisms. The encoded 206 amino acid protein lacks homology to any characterized protein sequence and is a disordered protein according to structure prediction algorithms. To identify interactions of MACIR with proteins from all subcellular compartments, a membrane solubilization buffer is employed, that together with a high affinity EF hand based pull down method, increases the resolution of quantitative mass spectrometry analysis with significant enrichment of interactions from membrane bound nuclear and mitochondrial compartments compared to samples prepared with radioimmunoprecipitation assay buffer. A total of 63 significant interacting proteins are identified and interaction with the nuclear transport receptor TNPO1 and the trafficking proteins UNC119 homolog A and B are validated by immunoprecipitation. Mutational analysis in two candidate nuclear localization signal motifs in the MACIR amino acid sequence shows the interaction with TNPO1 is likely via a non-classical proline/tyrosine-nuclear localization signal motif (aa98-117). It is shown that employing a highly specific and high affinity pull down method that performs efficiently in this glycerol and detergent rich buffer is a powerful approach for the analysis of uncharacterized protein interactomes.
33131691 The NZB/W F1 mouse model for Sjögren's syndrome: A historical perspective and lessons le 2020 Dec Sjögren's syndrome (SS) is a chronic rheumatic autoimmune disorder affecting multiple organ systems. The clinical findings in SS patients show considerable heterogeneity and overlap with other autoimmune diseases. In addition, the autoimmune response in SS initiates several years before the appearance of clinical symptoms. Thus, understanding the pathogenic mechanisms involved in the disease process have been a challenge. Several animal model systems of SS-like disease have been developed to overcome these issues. The New Zealand Black (NZB) x New Zealand White (NZW) F1 (NZB/W F1) mouse represents the first spontaneous mouse model of SS. In this review, we provide a historical perspective and detailed description of this mouse model focusing on exocrine gland histopathology, autoantibody populations, and glandular dysfunction. Considering that NZB/W F1 mice also develop a systemic lupus erythematosus (SLE)-like disease, this mouse model mimics the clinical presentation of polyautoimmunity seen in a sizable subset of SS patients. It is plausible that such patients will require distinct therapeutic interventions necessary to treat both SLE and SS. Therefore, the NZB/W F1 mouse is a powerful tool to decipher pathogenic mechanisms involved in SS related polyautoimmunity and develop appropriate therapeutic strategies.
33095145 Ultra-high frequency ultrasonography of labial glands is a highly sensitive tool for the d 2020 Jul OBJECTIVES: Ultra-high frequency ultrasonography (UHFUS) has been recently introduced in oral medicine due to its ability to image small anatomical structures including labial salivary glands (LSG). To date no ultrasonography morphological studies of labial salivary glands (LSG) have been carried out in SS. In this pilot study we aimed at analysing the distribution of UHFUS findings in LSG of patients with suspected SS, focusing in particular on the association with patients' oral dysfunction, antibody profiles and histopathology. METHODS: Consecutive patients undergoing a LSG biopsy for clinically suspected SS were included in this study between January 2018 and January 2020. Intraoral UHFUS scan of the lip mucosa was performed with Vevo MD equipment, using a 70 MHz probe with a standardised protocol. LSG were assessed by using a four-grade semiquantitative scoring system (0-3), similar to the OMERACT scoring system used for major salivary glands. The distribution of UHFUS grades was compared in patients stratified according their final diagnosis, patients antibody profiles and LSG histopathology. RESULTS: We included 128 patients with suspected SS: out of them, 54 (42.2%) received a final diagnosis of SS, made according to the ACR 2016 criteria and 74 (57.8%) were diagnosed as no-SS sicca controls. We found that LSG inhomogeneity was significantly greater in patients with SS than in no-SS subjects (p<0.0001). We also found that higher UHFUS pattern of inhomogeneity (i.e. grade 2 and 3) were significantly more frequent in both SSA+/SSB- and SSA+/SSB+ patients (p=0.001). A normal UHFUS pattern, by contrast, was significantly more common in SSA-/SSB- subjects (i.e. 15/83 (18.1%) vs. 1/33 (3%) vs. 0/12 (0%), p=0.001). Finally, LSG inhomogeneity was significantly associated with both the number of foci (p<0.001) and focus score (p<0.001). Particularly, we found that both the number of foci and the FS were significantly higher in patients presenting a UHFUS grading of 2 and 3 with respect to those presenting a UHFUS grading of 0 and 1 (p=0.01). CONCLUSIONS: This preliminary study demonstrates the optimal feasibility of UHFUS and its high sensitivity in identifying negative patients on subsequent lip biopsy, thus avoiding invasive procedures in selected cases. Further studies are in progress to define the clinical and predictive role of the various patterns observed and their added value with respect to traditional salivary gland ultrasonography.
32881834 Relationship between the use of Chinese herbal medicines and Sjögren syndrome risk among 2020 Aug 31 OBJECTIVE: Menopausal women appear to report a higher risk of Sjögren syndrome (SS). Although Chinese herbal medicines (CHMs) are proven to lower SS risk, the scientific evidence of whether it can lessen the occurrence of SS among menopausal women is limited. This longitudinal cohort study aimed to clarify the relationship between CHMs use and SS risk in menopausal women. METHODS: Using a nationwide claims data, we enrolled 31,917 women with first-time diagnosed menopause who simultaneously were free of SS between 2000 and 2007. Among them, we randomly selected 12,757 CHMs users and 12,757 non-CHMs users using propensity scores matching. All participants were followed until the end of 2012 to record SS incidence. The hazard ratio of SS with regard to CHMs use was estimated using the Cox proportional hazards regression model. RESULTS: In the follow-up period, 589 CHMs users and 644 non-CHMs users developed SS, representing incidence rates of 5.12 and 6.40, respectively, per 1,000 person-years. CHMs use was associated with a 21% lower subsequent risk of SS (adjusted hazard ratio, 0.79; 95% CI, 0.71-0.89). Six commonly prescribed CHMs were discovered to be associated with lower SS risk: Ge-Gen-Tang, Zhi-Gan-Cao-Tag, Da-Huang, Ye-Jiao-Teng, Tian-Hua-Fen, and Bo-Zi-Ren. CONCLUSIONS: A statistically significant association was found between CHMs use and lower risk of SS onset in menopausal women, suggesting that CHMs could be considered to integrate it into conventional therapy to reduce subsequent SS risk for menopausal women.
32571405 Identification of novel genes associated with dysregulation of B cells in patients with pr 2020 Jun 22 BACKGROUND: The aim of this study was to identify the molecular mechanism of dysregulation of B cell subpopulations of primary Sjögren's syndrome (pSS) at the transcriptome level. METHODS: We enrolled patients with pSS (n = 6) and healthy controls (HCs) (n = 6) in the discovery cohort using microarray and pSS (n = 14) and HCs (n = 12) in the validation cohort using quantitative PCR (qPCR). Peripheral B cells acquired from these subjects were separated by cell sorting into four subsets: CD38(-)IgD(+) (Bm1), CD38(+)IgD(+) (naive B cells), CD38(high)IgD(+) (pre-germinal centre B cells) and CD38(±)IgD(-) (memory B cells). We performed differentially expressed gene (DEG) analysis and weighted gene co-expression network analysis (WGCNA). RESULTS: Expression of the long non-coding RNA LINC00487 was significantly upregulated in all B cell subsets, as was that of HLA and interferon (IFN) signature genes. Moreover, the normalized intensity value of LINC00487 significantly correlated with the disease activity score of all pSS B cell subsets. Studies of human B cell lines revealed that the expression of LINC00487 was strongly induced by IFNα. WGCNA revealed six gene clusters associated with the B cell subpopulation of pSS. Further, SOX4 was identified as an inter-module hub gene. CONCLUSION: Our transcriptome analysis revealed key genes involved in the dysregulation of B cell subpopulations associated with pSS. TRIAL REGISTRATION: Not required.
31875749 Treatment of serologically negative Sjögren's syndrome with tacrolimus: A case report. 2020 Apr We herein report an unusual case of primary Sjögren's syndrome in a 38-year-old woman with typical clinical symptoms (joint pain, dry mouth, and positive Schirmer test) and immunoglobulin G positivity but negativity for antinuclear antibody and all antinuclear antibody spectrum antibodies. Emission computed tomography demonstrated normal ingestion but impaired secretion by the submandibular and bilateral parotid glands. Labial gland biopsy revealed chronic tissue inflammatory changes and Chisholm grade 4 lymphocyte infiltration, confirming primary Sjögren's syndrome. The patient's condition was successfully controlled by nonsteroidal treatment with tacrolimus. Patients presenting with chronic dry mouth should be examined by a Schirmer test, lip gland biopsy, and salivary gland emission computed tomography for possible Sjögren's syndrome, even if serological autoantibodies are negative, to facilitate early intervention. Tacrolimus is a potential treatment option in patients intolerant of steroidal drugs.
31875742 Ileocecal junction perforation by colonic T-cell lymphoma in a patient with primary Sjögr 2020 Apr Primary Sjögren's syndrome (pSS) is associated with an increased risk of lymphoma, especially non-Hodgkin's lymphoma. The rarest pathological subtype is T-cell lymphoma. We herein report a case of a 52-year-old man with a 17-year history of pSS who was admitted to our hospital with chronic epigastric pain and a positive fecal occult blood test. Colonoscopy revealed multiple colonic ulcers, and histological and immunological studies demonstrated the T-cell origin of this lymphoma. However, the patient rejected all treatments. He developed recurrent intestinal obstruction and infection for 3 years until an intestinal perforation occurred. The right half of the colon was resected and colostomy was performed. However, the patient died of an intestinal fistula and intraperitoneal infection 40 days postoperatively. This case highlights the rarity of the correlation between T-cell lymphoma and pSS.
33182021 LncRNA Neat1 positively regulates MAPK signaling and is involved in the pathogenesis of Sj 2020 Nov OBJECTIVE: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease characterized by lymphocytic infiltration of the exocrine glands. Recent, studies have shown that the long noncoding RNA (lncRNA) NEAT1 plays a crucial role in regulating the immune response. However, studies on the lncRNA NEAT1 in pSS are limited. Exploring the role of the lncRNA NEAT1 in the pathogenesis of pSS was the purpose of this study. METHODS: The expression of NEAT1 in peripheral blood mononuclear cells (PBMCs) of patients with pSS and healthy controls (HCs) was analyzed by real-time polymerase chain reaction (RT-PCR). Antisense oligonucleotides (ASOs) and siRNA or immune stimulation with PMA/ionomycin were used to perform loss-and-gain-of-function experiments. RT-PCR, enzyme-linked immunosorbent assay (ELISA), and Western blot were performed to detect the RNA and protein levels of specific genes induced by PMA/ionomycin stimulation. Microarray analysis was used to generate an overview of the genes that might be regulated by NEAT1. RESULTS: Compared with that in HC patient cells, the expression of NEAT1 in pSS patients was mainly increased in peripheral T cells, including CD4(+) and CD8(+) T cells. Additionally, the expression of NEAT1 in CD4(+) T cells of patients with pSS was positively correlated with the course of disease. NEAT1 expression in Jurkat cells was induced by PMA/ionomycin stimulation upon activation of the TCR-p38 pathway. Upregulation of NEAT1 expression also increased the expression of CXCL8 and TNF-α. Knocking down NEAT1 expression with an ASO suppressed the expression of CXCL8 and TNF-α in PMA/ionomycin-stimulated Jurkat cells. Then, we found that NEAT1 regulated the activation of MAPK pathway to regulate NEAT1-induced factors, selectively activating the expression of p-p38 and p-ERK1/2. Furthermore, we also detected the expression profile of Jurkat cells stimulated by PMA/ionomycin when NEAT1 was silenced or not, in order to produce an overview of NEAT1-regulated genes. CONCLUSION: These results provide a new understanding of the mechanisms of pSS and reveal that NEAT1 is a positive regulator of pSS, which is of substantial significance to its pathogenesis. Thus, NEAT1 provides a potential therapeutic target for pSS.
32366870 miR-744-5p contributes to ocular inflammation in patients with primary Sjogrens Syndrome. 2020 May 4 In primary Sjögren's syndrome (pSS) the exocrine glands become infiltrated with lymphocytes instigating severe damage to the salivary and lacrimal glands causing dry eyes and dry mouth. Previous investigations have suggested that dysregulated localized and systemic inflammation contributes to the development and pathogenesis of pSS. A miR microarray performed in primary human conjunctival epithelial cells (PECs) demonstrated significant differences in miR expression at the ocular surface between pSS patients and healthy controls. MicroRNA-744-5p (miR-744-5p) was identified as being of particular interest, as its top predicted target is Pellino3 (PELI3), a known negative regulator of inflammation. Validation studies confirmed that miR-744-5p expression is significantly increased in PECs from pSS patients, whilst PELI3 was significantly reduced. We validated the miR-744 binding site in the 3' untranslated region (UTR) of PELI3 and demonstrated that increasing PELI3 levels with a miR-744-5p antagomir in an inflammatory environment resulted in reduced levels of IFN dependent chemokines Rantes (CCL5) and CXCL10. These results reveal a novel role for miR-744-5p in mediating ocular inflammation via Pellino3 expression in pSS patients and suggest that miR-744-5p may be a potential therapeutic target for the management of severe dry eye disease and ocular inflammation in pSS patients.
31676972 Ultrasound salivary gland involvement in Sjogren's syndrome vs. other connective tissue di 2020 Apr This study aims to investigate ultrasound (US) findings on salivary glands (SG) in patients with Sjögren syndrome (SS) vs. other connective tissue diseases (CTDs) and to assess the relationship of SGUS abnormalities with autoantibody profile in both groups. We enrolled 81 patients, 45 diagnosed with SS (39 with primary SS, 6 with secondary SS) and 36 diagnosed with other CTDs. All patients underwent a prospective evaluation of sicca symptoms, a Schirmer's test, and a B-mode US assessment of the parotid and submandibular glands, all blinded to the diagnosis. Each SG was semi-quantitatively scored 0-3; a grade ≥ 2 was considered pathological. SGUS involvement was classified as normal or pathological at the patient level and for each pair at the gland level. In addition, a total SGUS score of 0-12 and a parotid/submandibular score of 0-6 were calculated for each patient. Autoimmunity laboratory data were also obtained. All SGUS scores were higher in SS patients than in those with CTD (p < 0.001) and significantly more SS patients showed a pathological global (p < 0.001), parotid (p < 0.001), or submandibular (p = 0.001) US score compared with CTD patients. In SS patients, the presence of autoantibodies was significantly associated with pathological SGUS and higher scores, particularly at the parotid level, while in CTD patients, xerostomia and a pathological Schirmer's test were associated with pathological US and higher scores at the submandibular level (p < 0.05). SGUS showed a different grade of abnormality, site involvement, and associated autoantibody profile in SS patients as compared with other CTD. KEY POINTS: • Patients with SS and other CTDs showed different grades of SGUS abnormality. • Patients with SS and other CTDs showed different gland involvement and associated autoantibody profiles. • Anti-Ro60 and anti-Ro52 Ro60 positivity were associated with the severity of parotid involvement in SS patients.
31504928 Can artificial intelligence replace manual search for systematic literature? Review on cut 2020 Apr 1 OBJECTIVES: Manual systematic literature reviews are becoming increasingly challenging due to the sharp rise in publications. The primary objective of this literature review was to compare manual and computer software using artificial intelligence retrieval of publications on the cutaneous manifestations of primary SS, but we also evaluated the prevalence of cutaneous manifestations in primary SS. METHODS: We compared manual searching and searching with the in-house computer software BIbliography BOT (BIBOT) designed for article retrieval and analysis. Both methods were used for a systematic literature review on a complex topic, i.e. the cutaneous manifestations of primary SS. Reproducibility was estimated by computing Cohen's κ coefficients and was interpreted as follows: slight, 0-0.20; fair, 0.21-0.40; moderate, 0.41-0.60; substantial, 0.61-0.80; and almost perfect, 0.81-1. RESULTS: The manual search retrieved 855 articles and BIBOT 1042 articles. In all, 202 articles were then selected by applying exclusion criteria. Among them, 155 were retrieved by both methods, 33 by manual search only, and 14 by BIBOT only. Reliability (κ = 0.84) was almost perfect. Further selection was performed by reading the 202 articles. Cohort sizes and the nature and prevalence of cutaneous manifestations varied across publications. In all, we found 52 cutaneous manifestations reported in primary SS patients. The most described ones were cutaneous vasculitis (561 patients), xerosis (651 patients) and annular erythema (215 patients). CONCLUSION: Among the final selection of 202 articles, 155/202 (77%) were found by the two methods but BIBOT was faster and automatically classified the articles in a chart. Combining the two methods retrieved the largest number of publications.
32996808 Detection of nerve enlargement with ultrasound and correlation with skin biopsy findings i 2021 Jul OBJECTIVES: We evaluated usefulness of peripheral nerve ultrasound (US) in detecting abnormality in painful sensory neuropathy (PSN) associated with primary Sjögren's syndrome (pSS), and associations among various clinical factors, US findings, and intraepidermal nerve fiber density (IENFD). METHODS: We conducted a retrospective, single-center, observational study of patients with pSS-PSN. US image was obtained to measure cross sectional area (CSA) of peripheral nerves and compared with matched pSS control. RESULTS: We included 11 patients with pSS-PSN (10 women; age 70.5 ± 5.66) and 17 pSS controls (15 women; age 62.5 ± 16.7). Sural nerve CSA were significantly increased in pSS-PSN group (3.48 ± 1.0 mm(2) vs 2.05 ± 0.65 mm(2), p = .001). US of sural nerve showed the area under the ROC curve of 0.872 (95% CI, 0.732 - 1). Sural nerve CSA and IENFD of lower leg showed positive correlation. Compared with pSS-PSN patients with abnormal IENFD, those with normal IENFD showed significantly larger sural nerve CSA, and trends toward less systemic disease activity and small fiber impairment with sparing of large fibers. CONCLUSION: US was useful in discriminating pSS patients with PSN from those without. Additionally, US may disclose distinct subsets of pSS-PSN with different clinical findings and IENFD.
31859545 Human umbilical cord mesenchymal stem cells confer potent immunosuppressive effects in Sjà 2021 Jan BACKGROUND: Primary Sjögren's syndrome (SS) is a lymphoproliferative disease with a chronic autoimmune disorder characterized by mononuclear cell (MNC) infiltration of notably the lacrimal and salivary glands. As mesenchymal stem cells (MSCs) regulate series of immunological responses partially by regulating proportion of CD4(+) T cells and inducing an immunosuppressive local milieu, umbilical cord MSCs (UC-MSCs) are being considered as a novel source for cell-based therapies against primary SS. This study aimed to investigate the feasibility of UC-MSCs in treatment of SS and to explore the possible mechanism(s) with the special emphasis on regulatory T cells (Tregs). METHODS: Potent immunosuppressive effects of human UC-MSCs on SS were explored in vivo and in vitro. To study the effects of human UC-MSCs on the development and progression of SS, human UC-MSCs were administered before disease onset (preventive protocol) and after disease occurrence (therapeutic protocol) in non-obese diabetic (NOD) mice. In human study, the effect of human UC-MSCs on T cells from SS patients was studied. RESULTS: In both protocols, the histopathology of submandibular and sublingual salivary glands showed decreased inflammatory infiltrates. In vitro, human UC-MSCs exhibited potent suppressive effects on responses of MNCs in NOD mice and T cells in SS patients. Such inhibitory effects were coupled with decreased production of proinflammtory cytokines interferon-γ, interleukin (IL)-6, tumor necrosis factor-α and increased production of IL-10 (n = 10, p < .01). The frequency of CD4(+)Foxp3(+)T cells in the spleen of NOD recipients was elevated (n = 6, p < .05). CONCLUSION: Human UC-MSCs are capable of inducing CD4(+)Foxp3(+) T cells in both NOD mice and human in vitro. Human UC-MSCs effectively interfere with the autoimmune attack in the course of SS by inducing an in vivo state of T cell unresponsiveness and the upregulation of Tregs.
33552062 Cytokine Storm in Coronavirus Disease 2019 and Adult-Onset Still's Disease: Similarities a 2020 The catastrophic outbreak of coronavirus disease 2019 (COVID-19) is currently a public emergency. Adult-onset Still's disease (AOSD) is an autoinflammatory disease characterized by life-threatening complications. Systemic hyperinflammation and cytokine storm play a critical role in the pathogenesis of both COVID-19 and AOSD. We aimed to compare the similarities and differences focusing on ferritin and cytokine levels between severe COVID-19 and active AOSD. A literature search was performed using the databases PubMed, EMBASE, and Web of Science to collect the levels of cytokine including IL-1β, IL-6, IL-18, TNF-α, IL-10, and ferritin in severe COVID-19 patients. After extracting available data of indicators of interest, we acquired these statistics with a single-arm meta-analysis. Furthermore, a comparison was conducted between 52 patients with active AOSD in our center and severe COVID-19 patients from databases. The levels of IL-6 and IL-10 were higher in severe COVID-19 compared with those in active AOSD. There were no significant differences on the cytokine of IL-1β and TNF-α. Fold changes of IL-18 were defined as the mean expression level ratio of severe COVID-19 to healthy controls in the COVID-19 study and active AOSD to healthy controls in our study, individually. Although the fold change of IL-18 in patients with AOSD was significantly higher than patients with severe COVID-19 (fold change: 594.00 vs 2.17), there was no statistical comparability. In addition, the level of ferritin was higher in active AOSD in comparison with severe COVID-19. Our findings suggest that severe COVID-19 and active AOSD have differences in cytokine panel and ferritin level, indicating the pathogenic role of ferritin in overwhelming inflammation. And it paves the way to make efficacy therapeutic strategy targeting the hyperinflammatory process in COVID-19 according to AOSD management, especially in severe COVID-19.
32200426 Shear wave elastography as a new method to identify parotid lymphoma in primary Sjögren S 2020 Aug Parotid non-Hodgkin lymphoma (NHL) in primary Sjögren syndrome (pSS) has no specific biomarker for diagnosis. Salivary glands ultrasound (US) is largely used, but its contribution in detecting parotid NHL has not been established. The aim of our study was to determine the added value of bidimensional shear wave elastography (2D-SWE) in pSS diagnosis and to determine its accuracy in identifying parotid NHL. Grey-scale US (GSUS) and 2D-SWE of salivary glands were performed in 35 patients with pSS and 35 healthy controls. The GSUS scores were calculated and the mean of three SWE consecutive measurements was used to appreciate the gland stiffness. SWE increase the diagnostic rate at a cut-off of 6.45 kPa (from 88.6 to 94.2%, p < 0.001) only if applied in patients with insufficient GSUS criteria for pSS diagnosis. The parotid glands with NHL (8 patients, all mucosa-associated lymphoid tissue type) had hyperechoic bands in more than half of the glandular parenchyma (in 68.75% of the glands), large hypoechoic area > 20 mm (all glands), traced gland area over 5 cm(2) (all glands), parotid US score greater than 13 (in 68.75% of the glands), and high stiffness (elasticity modulus 13.9 ± 4.08 vs 6.32 ± 2.24) (all p < 0.001). These findings give high sensitivity (92.3%), specificity (100%), and positive (100%) and negative predictive values (98.3%) for NHL identification. The rest of GSUS findings did not correlate with the classic risk factors for lymphoma development (all p > 0.05). 2D-SWE had added value for pSS diagnosis in cases where GSUS aspect is normal or nonspecific. The higher stiffness of parotid NHL can be used for early diagnosis, biopsy guidance, and, possible, for treatment monitoring.
32100426 Characteristics of diffuse large B-cell lymphoma in patients with primary Sjögren's syndr 2020 Apr AIM: Patients with primary Sjögren's syndrome (pSS) have an increased risk of developing diffuse large B-cell lymphoma (DLBCL), which is an aggressive and heterogeneous non-Hodgkin lymphoma. This study aimed to characterize DLBCLs in patients with pSS. METHOD: We identified 18 patients with DLBCL and pSS over a 22-year period. Based on the 2016 WHO guidelines, we characterized DLBCL based on immunohistochemical tests using a broad panel of antibodies, and an Epstein-Barr virus (EBV) test using in situ hybridization. RESULTS: The median time from initial pSS symptom onset to the DLBCL diagnosis was 20.5 years and the median time from the pSS diagnosis until the DLBCL diagnosis was 14 years. After the lymphoma diagnosis, the median overall survival was 3 months (range: 0-212 months) and the 5-year overall survival rate was 37.5%. Thirteen DLBCLs were re-classified as DLBCL, not otherwise specified (NOS) in nine cases; EBV-positive DLBCL, NOS in two cases; and T-cell/histiocyte-rich large B-cell lymphoma in two cases. Five cases of DLBCLs were not re-classified because their EBV status was unknown. The Hans algorithm, which uses a combination of staining for CD10, BCL6, and MUM1, was used to classify the DLBCLs into the germinal center B-cell (GCB) subtype for three cases and the non-GCB subtype for nine cases. CONCLUSION: These results indicate that DLBCL tends to occur late in pSS cases and is mainly related to the non-GCB subtype of DLBCL.
34301381 Validation and adaptation to Spanish of the EULAR Sjögren's Syndrome Patient Reported Ind 2021 Aug INTRODUCTION AND OBJECTIVES: Sjögren's Syndrome (SS) is an autoimmune disease with a wide spectrum of clinical manifestations that can have an important impact on the patient's quality of life. To make an objective evaluation of the components of the disease, clinimetric tools such as the ESSPRI have been designed. The objective of this study is to adapt this scale to the Spanish language. MATERIALS AND METHODS: This is a cross-sectional study to validate clinimetric scales, carried out in Cali, Colombia. A translation of the original English version of ESSPRI into Spanish was made and applied to patients with SS, as well as PROFAD and ESSDAI, as an activity marker. The reliability index of the questionnaire in Spanish with Cronbach's alpha coefficient and Spearman's correlation coefficient were calculated to compare the scales. Demographic, clinical and laboratory characteristics were also evaluated. RESULTS: ESSPRI, PROFAD and ESSDAI were applied to 42 patients with SS, 97.62% were women. The average result of the ESSPRI was 5.8 (± 4.6), with a reliability coefficient of .8034 and a correlation with PROFAD of .5800 (p=.0001), and of -.0848 (p=.593) with ESSDAI. DISCUSSION AND CONCLUSIONS: Reliability with the applied version of ESSPRI in Spanish was adequate. A discrepancy was found between this scale and ESSDAI, which highlights the importance of applying both tools to ensure objective monitoring of disease control and its impact on the quality of life of patients with SS.
33033617 Emerging insights on the role of gasdermins in infection and inflammatory diseases. 2020 The gasdermins, family of pore-forming proteins, are emerging key regulators of infection, autoinflammation and antitumor immunity. Multiple studies have recently characterised their crucial roles in driving pyroptosis, a lytic pro-inflammatory type of cell death. Additionally, gasdermins also act as key effectors of NETosis, secondary necrosis and apoptosis. In this review, we will address current understanding of the mechanisms of gasdermin activation and further describe the protective and detrimental roles of gasdermins in host defence and autoinflammatory diseases. These data suggest that gasdermins play a prominent role in innate immunity and autoinflammatory disorders, thereby providing potential new therapeutic avenues for the treatment of infection and autoimmune disease.
32849899 The Derivative of Tripterygium wilfordii Hook F-Kunxian Capsule, Attenuated Rheumatoid Art 2020 The study aimed to explore the efficacy and safety of Kunxian Capsule (KXC) in the treatment of rheumatoid arthritis (RA). The randomized controlled trials (RCTs) comparing the effects of KXC in patients with RA were included in this study. Weighted mean differences (MDs) were calculated for net changes by employing Review Manager meta-analysis software. Nine RCTs were included in the systematic review with a total of 747 patients. The overall effects showed that KXC alone or combined with disease-modifying antirheumatic and drugs decreased tender joint counts (P=0.02, MD = -1.07, 95% CI: -1.95 to -0.18), shortened duration of morning stiffness (P < 0.0001, MD = -9.01, 95% CI: -13.08 to -4.93), lowered erythrocyte sedimentation rate (P < 0.00001, MD = -5.27, 95% CI: -6.78 to -3.77), and reduced C-reactive protein (P < 0.0001, MD = -5.04, 95% CI: -7.28 to -2.80). The most common adverse events were gastrointestinal disturbances and abnormal liver function. These results suggest that KXC is likely to be a more effective and safe candidate for treating RA compared with conventional therapies.
32716841 Insufficiency fractures of the knee, ankle, and foot in rheumatoid arthritis: A case serie 2020 Jul OBJECTIVE: To evaluate cases of insufficiency fractures verified by magnetic resonance imaging (MRI) of the knee, ankle, and foot in patients with rheumatoid arthritis (RA) cared for in our clinic over an 8-year period, to identify possible risk factors, and to test these in a case-control study. METHODS: All patients in the rheumatology clinic with RA were registered prospectively in the database, DANBIO. All MRIs ordered from the clinic were registered and coded according to the anatomical region. We were thus able to retrieve all patients with RA and performed an MRI of the knee or ankle/foot. The patients with fractures constituted the case series, and the patients without fractures constituted the control group. RESULTS: The RA clinic population comprised 1,624 patients who underwent a total of 70 MRIs. CASE SERIES: 39 insufficiency fractures were identified in 32 patients; 93% were women, and the median age was 68 years (range 33-89 years). Half of the patients had a T score >-2.5. The case control group without fractures comprised 38 patients; 74% were women, and the median age was 62 years (range 32-84 years). In the case series, 20 patients experienced later additional episodes of insufficiency fractures in the knee, ankle, or foot. CONCLUSION: Insufficiency fractures of the knee, ankle, and foot are a significant cause of pain and long-lasting disability in RA. Recurrent fractures are common. Diagnosis is often delayed and confused with arthritic activity. Conventional radiography and DEXA scan are often normal. Older age, female gender, radiological erosions in hand/wrist, and treatment with methotrexate were all significantly associated with fractures.