Applications of Proteomics, Glycomics, and Metabolomics Analyses in Systemic Lupus Erythematosus.

Systemic lupus erythematosus in a 15-year-old with graft-versus-host disease following liver transplant and unexpected full hematopoietic engraftment

Atherosclerosis is an inflammatory disease and the major cause of cardiovascular disease (CVD) in general. Atherosclerotic plaques are characterized by the presence of activated immune competent cells, but antigens and underlying mechanisms causing this immune activation are not well defined. During recent years and with improved treatment of acute disease manifestations, it has become clear that the risk of CVD is very high in a prototypic autoimmune disease, systemic lupus erythematosus (SLE). SLE-related CVD and atherosclerosis are important clinical problems but may in addition also shed light on how immune reactions are related to premature atherosclerosis and atherothrombosis. A combination of traditional and nontraditional risk factors, including dyslipidaemia (and to a varying degree hypertension, diabetes and smoking), inflammation, antiphospholipid antibodies (aPL) and lipid oxidation are related to CVD in SLE. Premature atherosclerosis in some form leading to atherothrombosis is likely to be a major underlying mechanism, though distinctive features if any, of SLE-related atherosclerosis when compared with 'normal' atherosclerosis are not clear. One interesting possibility is that factors such as inflammation or aPL make atherosclerotic lesions in autoimmune disease more prone to rupture than in 'normal' atherosclerosis. Whether premature atherosclerosis is a general feature of SLE or only affects a subgroup of patients remains to be demonstrated. Treatment of SLE patients should also include a close monitoring of traditional risk factors for CVD. In addition, attention should also be paid to nontraditional risk factors such as inflammation and SLE-related factors such as aPL. Hopefully novel therapeutic principles will be developed that target the causes of the inflammation and immune reactions present in atherosclerotic lesions.

Based on strong research evidence and consensus, the most common disease manifestations at diagnosis of pSLE are constitutional symptoms, arthritis, and malar rash. Based on some research evidence and consensus, patients with pSLE tend to have major organ system involvement (renal/central nervous system) and a greater disease burden compared with adults. Despite these findings, mortality is low. Based on some research evidence and consensus, the diagnosis of pSLE is unlikely if the ANA is negative, and most patients with SLE have a positive ANA at a titer ≥1:160. Based on strong research evidence, both MMF and cyclophosphamide can be used for induction therapy in class III and IV lupus nephritis. Based on strong research evidence, patients with SLE and anticardiolipin antibodies or LA have a two and six times greater risk of venous thrombosis, respectively, compared with patients with SLE without antiphospholipid antibodies. Based on strong research evidence, patients with pSLE have a higher risk for subclinical atherosclerosis when there is weight-adjusted prednisone use, azathioprine use, increasing age, male gender, high BMI, abnormal creatinine clearance, and elevated lipoprotein(a) levels.

BACKGROUND AND OBJECTIVESSystemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by humoral autoimmunity. The etiology of SLE is thought to be multifactorial including environmental, hormonal, and genetic factors. The human leukocyte antigen (HLA) has extensively been associated with the susceptibility to SLE; however, the association is heterogeneous among different ethnic groups. The aim of this study was to determine the association of HLA-A, HLA-B, HLA-DRB1, and HLA-DQB1 with SLE susceptibility in the Saudi population.DESIGN AND SETTINGSA total of 86 consecutive SLE patients attending the rheumatology clinic at King Abdulaziz Medical City, Riyadh, were recruited for this study.METHODSHLA types were determined by the polymerase chain reaction sequence-specific oligonucleotide (PCR-SSP) method in 86 patients and 356 control subjects.RESULTSThe following HLA alleles were found to be positively associated with SLE: HLA-A*29 (OR=2.70; 95% CI=1.03–7.08; P=.0035), HLA-B*51 (OR=1.81; 95% CI=1.17–2.79; P=.0066), HLA-DRB1*15 (OR=1.45; 95% CI=0.98–2.29; P=.063), and HLA-DQB1*06 (OR=1.67; 95% CI=1.19–2.36; P=.0032), whereas HLA-DRB1*16 was negatively associated with the disease (OR=0.18; 95% CI=0.02–1.3; P=.055). HLA-DRB1*15 haplotypes were significantly associated with SLE (OR=2.01, 95% CI=1.20–3.68, P=.008); this was mainly due to the HLA-DRB1* 15-DQB1*06 association.CONCLUSIONSOur data suggest an association between MHC class I and class II (HLA-A*29, HLA-B*51, HLA-DRB1*15, and HLA-DQB1*06) and susceptibility to SLE in the Saudi population. HLA-DRB1*15-DQB1*06 haplotype showed the highest risk factor for the disease that is similar to what was seen in the African American patients, suggesting shared susceptibility genetic factors among these ethnic groups.

S2k guideline: Diagnosis and management of cutaneous lupus erythematosus - Part1: Classification, diagnosis, prevention, activity scores.

Immunologic rheumatic disorders

Background:Systemic lupus erythematosus (SLE) is a systemic autoimmune disease caused by immune dysregulation and characterized by the production of a large number of autoantibodies leading to multiple organ involvement. Despite...

Small non-coding RNA molecules (miRs) are involved in immune cell maturation and function and might influence immunopathological processes of systemic lupus erythematosus (SLE) pathogenesis. This paper presents the results of a literature search for publications dealing with the relationship between miRs and pathological factors related to SLE such as genetic background, immune dysregulation and gender-associated differences participating in SLE development. In SLE, distinct miRs are differentially expressed in SLE cells of innate and adaptive immunity. The miR-146a and miR-155 genes, among others, interfere with intracellular signalling pathways downstream of toll-like receptors 7 and 9 (TLR- 7, TLR-9) and influences interferon (IFN)-type I synthesis in plasmacytoid dendritic cells. In T and B cells, miR-126, miR-21, miR-146a, miR-155, miR-1246 and others might influence gene expression by epigenetic modifications, support abnormal cytosine release, differentiation of cell subsets, B cell hyperactivity and autoantibody production. Besides, estrogen might up- and downregulate immunologically active miRs, which are potential mediators of hormonal influences in SLE development. Moreover, SLE genetic basis included some polymorphisms of the miR-146a gene, which varies across populations. Distinct miRs are differentially expressed in both SLE mice models and human patients and promote autoimmune features of immune processes. MiRs are important molecules modulating susceptibility to SLE as well as its onset, clinical diversity and progression.

Background:Systemic lupus erythematosus (SLE) is a multifactorial chronic autoimmune disease characterized by heterogeneous clinical manifestations [1]. Despite extensive research into its pathogenesis, the exact mechanisms underlying SLE remain incompletely understood,...

Prioritizing endocrine-disrupting chemicals targeting systemic lupus erythematosus genes via Mendelian randomization and colocalization analyses.

BackgroundIt is well known that genetic factors and environmental triggers contribute to the inflammatory process and onset of systemic lupus erythematosus (SLE). Yet, other contributors may still be unknow, and...

B cells twist and shout

The biological mechanism underlying the pathogenesis of systemic lupus erythematosus (SLE) remains unclear. In this study, we found 21 proteins upregulated and 38 proteins downregulated by SLE relative to normal protein metabolism in our samples using liquid chromatography-mass spectrometry. By PPI network analysis, we identified 9 key proteins of SLE, including AHSG, VWF, IGF1, ORM2, ORM1, SERPINA1, IGF2, IGFBP3, and LEP. In addition, we identified 4569 differentially expressed metabolites in SLE sera, including 1145 reduced metabolites and 3424 induced metabolites. Bioinformatics analysis showed that protein alterations in SLE were associated with modulation of multiple immune pathways, TP53 signaling, and AMPK signaling. In addition, we found altered metabolites associated with valine, leucine, and isoleucine biosynthesis; one carbon pool by folate; tyrosine metabolism; arginine and proline metabolism; glycine, serine, and threonine metabolism; limonene and pinene degradation; tryptophan metabolism; caffeine metabolism; vitamin B6 metabolism. We also constructed differently expressed protein-metabolite network to reveal the interaction among differently expressed proteins and metabolites in SLE. A total of 481 proteins and 327 metabolites were included in this network. Although the role of altered metabolites and proteins in the diagnosis and therapy of SLE needs to be further investigated, the present study may provide new insights into the role of metabolites in SLE.

Systemic lupus erythmatosus (SLE) is a multi-system autoimmune disease characterized by auto-reactive cells and auto-antibodies, which can potentially affect all organ systems. Typical organ systems that are affected include the heart, lungs, skin, kidneys, and central nervous system. Its expression is believed to be dependent on various factors such as genetic predisposition, environmental agents, immune dysregulation, crossreactivity with auto-antigens, alterations in auto-antigens, or most likely, a combination of these. Parvovirus B19, a virus which commonly runs an asymptomatic or benign self-limiting course such as erythema infectiosum, transient aplastic crisis, flu-like symptoms, rash, arthalgia, and arthritis, has recently been associated with a number of rheumatic diseases, more specifically with SLE. Like SLE, it can present with multi- systemic symptoms resembling SLE both clinically and serologically. Similarities have been so striking that patients have been initially misdiagnosed with SLE, having fulfilled 3-5 of the criteria of the American College of Rheumatology, currently used for the diagnosis of SLE, only to discover later that they were infected by parvovirus B19. This paper will discuss parvovirus' link to SLE, its similarities and differences, and whether parvovirus can act as a trigger of, or simply mimic, SLE.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that predominantly affects women of childbearing age and is characterized by the damage to multiple target organs. The pathogenesis of SLE is complex, and its etiology mainly involves genetic and environmental factors. At present, there is still a lack of effective means to cure SLE. In recent years, growing evidence has shown that gut microbiota, as an environmental factor, triggers autoimmunity through potential mechanisms including translocation and molecular mimicry, leads to immune dysregulation, and contributes to the development of SLE. Dietary intervention, drug therapy, probiotics supplement, fecal microbiome transplantation and other ways to modulate gut microbiota appear to be a potential treatment for SLE. In this review, the dysbiosis of gut microbiota in SLE, potential mechanisms linking gut microbiota and SLE, and immune dysregulation associated with gut microbiota in SLE are summarized.