Systemic lupus erythematosus associated with sarcoidosis: Case report

BackgroundThe association between systemic lupus erythematosus (SLE) and sarcoidosis has been considered as extremely rare. Most often, sarcoidosis coexists with Sjögren's syndrome. Researching the literature, it seems that the association of SLE and sarcoidosis is much more frequent than previously thought.Aim of the workWe present a case of a Serbian woman who was diagnosed with coexisting sarcoidosis and long-standing SLE.Case presentationThe 40 years old SLE patient was in long-standing remission on oral prednisolone (10 mg/day) and hydroxychloroquine (HCQ) (400 mg/day). She presented with fatigue, chest pain, and dry cough. Chest computerized tomography (CT) showed hilar and mediastinal lymphadenopathy. The biopsy had been performed and results showed sarcoidosis. Diagnosis has been confirmed: eosinophilic granulomas without central necrosis morphologically corresponding to chronic granulomatous lymphadenitis like sarcoidosis. Thereafter, the patient was hospitalized. No new symptoms appeared, and the physical examination was unremarkable. Serum calcium was elevated (2.75 mmol/l), anti-nuclear antibody (ANA), anti-double stranded deoxyribonucleic acid (anti-dsDNA) and anti-Ro antibodies were positive. Angiotensin converting enzyme (ACE) level was high normal (51 IU/L) and QuantiFERON-TB Gold test negative. The dose of prednisolone was increased to 40 mg/day with HCQ and the patient was discharged from hospital. On follow-up the patient improved with reduction of the steroid dose.ConclusionThe association of SLE and sarcoidosis should be considered even though it is reported to be extremely rare. May be the real incidence of these combinations is underestimated. More research about genetics and pathogenesis is needed to completely understand these conditions.     

Methodological Quality Assessment of Meta-analyses and Systematic Reviews of the Relationship Between Periodontal and Systemic Diseases

ObjectivesThe aims of this article are to identify all the published systematic reviews (SRs) and meta-analyses (MAs) that studied the relationship between periodontal and systemic diseases and to assess their quality using 2 scales (the Overview Quality Assessment Questionnaire [OQAQ] and A Measurement Tool to Assess Systematic Reviews [AMSTAR] checklist).MethodsFor SRs and MAs to be included, they should have investigated one of the following systemic diseases: pulmonary conditions, cardiac conditions, endocrine conditions, cancer, blood disorders, psychological conditions, anxiety, depression, mood disorders, and several other diseases. Two investigators screened MEDLINE via PubMed, Embase, Scopus, Web of Science, and the Cochrane Database of Systematic Reviews. The tools used to evaluate quality were the AMSTAR scale and OQAQ. The protocol was prospectively registered in PROSPERO (CRD42018102208).ResultsThe search strategy found 691 unique articles, 42 of which met the eligibility criteria and were included in this review. Diabetes mellitus was the most investigated disease (14 out of 42 studies), followed by obesity (11 studies) and cardiovascular diseases (5 studies). A total of 40 reviews reported on the characteristics of included studies, and, as per the AMSTAR scale, 39 reviews had an a priori design. The number of reviews that fulfilled the status of publication criterion was the lowest (7 reviews only), followed by the number used in the assessment of publication bias (11 reviews). The number of high-quality reviews was higher with the OQAQ than with the AMSTAR checklist (33 vs 25 studies), but the AMSTAR showed a higher number of medium-quality reviews than the OQAQ (14 vs 6 studies). Both showed the same number of low-quality reviews.ConclusionsHigh-quality SRs and MAs are crucial to understanding the relationship between systemic and periodontal diseases. Medical practitioners must be able to inform patients about oral health and specific periodontal health concerns.     

Identification of key genes and pathways in discoid lupus skin via bioinformatics analysis

Discoid lupus erythematosus (DLE) is the most common skin manifestation of lupus; however, the molecular mechanisms underlying DLE remain unknown. Therefore, we aimed to identify key differentially expressed genes (DEGs) in discoid lupus skin and investigate their potential pathways.To identify candidate genes involved in the occurrence and development of the disease, we downloaded the microarray datasets {"type":"entrez-geo","attrs":{"text":"GSE52471","term_id":"52471"}}GSE52471 and {"type":"entrez-geo","attrs":{"text":"GSE72535","term_id":"72535"}}GSE72535 from the Gene Expression Database (GEO). DEGs between discoid lupus skin and normal controls were selected using the GEO2R tool and Venn diagram software (http://bioinformatics.psb.ugent.be/webtools/Venn/). The Database for Annotation, Visualization, and Integrated Discovery (DAVID), Enrichr, and Cytoscape ClueGo were used to analyze the Kyoto Encyclopedia of Gene and Genome pathways and gene ontology. Protein-protein interactions (PPIs) of these DEGs were further assessed using the Search Tool for the Retrieval Interacting Genes version 10.0.Seventy three DEGs were co-expressed in both datasets. DEGs were predominantly upregulated in receptor signaling pathways of the immune response. In the PPI network, 69 upregulated genes were selected. Furthermore, 4 genes (CXCL10, ISG15, IFIH1, and IRF7) were found to be significantly upregulated in the RIG-I-like receptor signaling pathway, from analysis of Enrichr and Cytoscape ClueGo.The results of this study may provide new insights into the potential molecular mechanisms of DLE. However, further experimentation is required to confirm these findings.     

Neutrophil proteases degrade autoepitopes of NET-associated proteins

Neutrophils can form neutrophil extracellular traps (NETs) to capture microbes and facilitate their clearance. NETs consist of decondensed chromatin decorated with anti-microbial proteins. Here, we describe the effect of neutrophil proteases on the protein content of NETs. We show that the neutrophil serine proteases degrade several neutrophil proteins associated with NETs. Interestingly, the anti-bacterial proteins associated with NETs, such as myeloperoxidase, calgranulin B and neutrophil elastase (NE), seem to be less susceptible to proteolytic degradation than other NET proteins, such as actin and MNDA. NETs have been proposed to play a role in autoimmune reactions. Our data demonstrate that a large number of the autoepitopes of NET proteins that are recognized by autoantibodies produced by systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients are also removed by the proteases. In conclusion, neutrophil serine proteases have a major impact on the NET proteome and the proteolytic changes of NET-associated proteins may counteract autoimmune reactions to NET components.     

The association between the decreased expression levels of FOXJ1 and the activation of NF-κB pathway in interstitial lung disease of MRL/Lpr mice

Background: Pulmonary manifestations of systemic lupus erythematosus (SLE) are appearing in 4-5% of patients involving lung in almost half of the cases during the disease course. Objective: We compared the autoimmune pulmonary inflammation in the lung tissue of mice to determine the association between decreased expression levels of Forkhead Box J1 (FOXJ1) and the activation of the NF-κB pathway in autoimmune pulmonary inflammation of MRL/Lpr mice. Methods: The female BALB/c mice (n=6) and MRL/Lpr mice (n=30) were divided into 5 groups including a control group (BALB/c), and five MRL/Lpr mice groups (8W, 12W, 16W, 24W, and 32W). The infiltration of the inflammatory cells was determined in lung tissue by performing the histological analysis. The western blotting was used to examine the expression levels of the age-related FOXJ1, and p50 and p65 proteins in the lungs of MRL/Lpr mice. The expression levels of MMP2 and MMP9 were determined via immunohistochemistry and immunofluorescence. Results: There were severe infiltrates of lung cells with high levels of tracheal damage, perivascular injury and interstitial inflammatory cell infiltration when the MRL/Lpr mice from 16w to 32w comparing to the 8w old healthy MRL/Lpr mice in the control group (p <0.05). Moreover, the reduced expression levels of FOXJ1 were associated with the activation of the NF-κB pathway in interstitial lung disease of MRL/Lpr mice via the modulation of p50 and p65. In addition, the expression levels of MMP2 and MMP9 pro-inflammation factors increased in the lungs of the MRL/Lpr mice from 16w to 32w. Conclusions: The expression level of FOXJ1 might be an indicator of the degree of lung disease in lupus-prone mice.