scholarly journals Autoantibody to MDM2: A Potential Serological Marker of Systemic Lupus Erythematosus

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Yuan Liu ◽  
Liping Dai ◽  
Weihong Liu ◽  
Guixiu Shi ◽  
Jianying Zhang
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Immunofluorescence Assay ◽  
Negative Regulator ◽  
Autoimmune Response ◽  
Nuclear Staining ◽  
Systemic Lupus ◽  
Autoantibody Production ◽  
High Prevalence ◽  
Healthy Persons

Introduction.Systemic lupus erythematosus (SLE) is one of the systemic autoimmune diseases characterized by the polyclonal autoantibody production. The human homologue of the mouse double minute 2 (MDM2) is well known as the negative regulator of p53. MDM2 has been reported to be overexpressed in SLE animal model and to promote SLE. Since abnormally expressed proteins can induce autoimmune response, anti-MDM2 autoantibody was examined in SLE patients.Methods.Anti-MDM2 antibody in sera from 43 SLE patients and 69 healthy persons was investigated by ELISA. Positive samples were further confirmed by western blotting. The immunological feathers of anti-MDM2 positive sera were analyzed by indirect immunofluorescence assay. Anti-p53 was also investigated in SLE patients by ELISA, and the correlation of anti-MDM2 and anti-p53 was analyzed.Results.The presence of anti-MDM2 in SLE patients was 23.30%, much higher than normal healthy persons (4.30%). These anti-MDM2 positive sera present a nuclear staining pattern. The presence of anti-p53 in SLE patients was 39.50%, and the titer of anti-MDM2 was positively correlated with anti-p53 in SLE patients.Conclusions.Anti-MDM2 autoantibody was detected at high prevalence in SLE patients. The detection of anti-MDM2 in SLE patients should be clinically useful.

scholarly journals Leptin promotes systemic lupus erythematosus by increasing autoantibody production and inhibiting immune regulation

2016 ◽  
Vol 113 (38) ◽  
pp. 10637-10642 ◽  
Author(s):  
Elaine V. Lourenço ◽  
Aijing Liu ◽  
Giuseppe Matarese ◽  
Antonio La Cava
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
New Zealand ◽  
Renal Disease ◽  
Lupus Erythematosus ◽  
Cellular Level ◽  
Presentation Of Self ◽  
Systemic Lupus ◽  
Autoantibody Production

Leptin is an adipocytokine that plays a key role in the modulation of immune responses and the development and maintenance of inflammation. Circulating levels of leptin are elevated in systemic lupus erythematosus (SLE) patients, but it is not clear whether this association can reflect a direct influence of leptin on the propathogenic events that lead to SLE. To investigate this possibility, we compared the extent of susceptibility to SLE and lupus manifestations between leptin-deficient (ob/ob) and H2-matched leptin-sufficient (wild-type, WT) mice that had been treated with the lupus-inducing agent pristane. Leptin deficiency protected ob/ob mice from the development of autoantibodies and renal disease and increased the frequency of immunoregulatory T cells (Tregs) compared with leptin-sufficient WT mice. The role of leptin in the development of SLE was confirmed in the New Zealand Black (NZB) × New Zealand White (NZW)F1 (NZB/W) mouse model of spontaneous SLE, where elevated leptin levels correlated with disease manifestations and the administration of leptin accelerated development of autoantibodies and renal disease. Conversely, leptin antagonism delayed disease progression and increased survival of severely nephritic NZB/W mice. At the cellular level, leptin promoted effector T-cell responses and facilitated the presentation of self-antigens to T cells, whereas it inhibited the activity of regulatory CD4 T cells. The understanding of the role of leptin in modulating autoimmune responses in SLE can open possibilities of leptin-targeted therapeutic intervention in the disease.

scholarly journals Serum immunoglobulin a deficiency and autoimmune comorbidities: a crossectional study in 281 patients with systemic lupus erythematosus

2020 ◽  
Vol 66 (6) ◽  
pp. 752-756
Author(s):  
Gustavo Felício Alexandroni Linzmeyer ◽  
Fabiane Karen Miyake ◽  
Thiago Alberto F. C. Gomes Dos Santos ◽  
Thelma L Skare
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Autoimmune Disease ◽  
Autoimmune Diseases ◽  
Clinical Data ◽  
Lupus Erythematosus ◽  
Immunoglobulin A ◽  
Hashimoto Thyroiditis ◽  
Iga Deficiency ◽  
Systemic Lupus ◽  
High Prevalence

SUMMARY OBJECTIVE To study the profile of associated autoimmune diseases in a series of patients with systemic lupus erythematosus (SLE) and see if such associations are linked to IgA deficiency. METHODS Two hundred eighty-one patients with SLE were studied for Ig A levels by nephelometry. Levels equal to or under 0.05g/dL were considered as IgA deficiency. Epidemiological and clinical data, including the presence of associated autoimmune diseases, were extracted from the patient’s charts. RESULTS Ig A deficiency was found in 6% of the patients. In 30.2% of SLE patients, there was at least one more autoimmune disease; Hashimoto thyroiditis and Sjögren’s syndrome were the most common. No association between the occurrence of associated autoimmune disease with IgA deficiency was found. CONCLUSIONS There is a high prevalence of autoimmune diseases associated with SLE. IgA deficiency does not affect the presence of these associations.

scholarly journals High IgA antiphospholipid autoantibodies in healthy Sudanese explain the increased prevalence among Sudanese compared to Swedish systemic lupus erythematosus patients

Lupus ◽  
2020 ◽  
Vol 29 (11) ◽  
pp. 1412-1422 ◽  
Author(s):  
Sahwa Elbagir ◽  
Amir I Elshafie ◽  
Elnour M Elagib ◽  
NasrEldeen A Mohammed ◽  
Mawahib IE Aledrissy ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
South African ◽  
Lupus Erythematosus ◽  
Fetal Loss ◽  
African Origin ◽  
Systemic Lupus ◽  
American College Of Rheumatology ◽  
Glycoprotein I ◽  
High Prevalence ◽  
Clinical Associations

Objectives IgA antiphospholipid antibodies (aPL) are prevalent in systemic lupus erythematosus (SLE) patients of African American, Afro-Caribbean and South African origin. Nevertheless, data from North Africa are lacking, and most studies use manufacturer-suggested cut-offs based on Caucasian controls. Therefore, we compared aPL isotypes in Sudanese and Swedish SLE patients using nation-based cut-offs. Methods Consecutive SLE patients and age- and sex-matched controls from Sudan ( N = 115/106) and Sweden ( N = 340/318) were included. All patients fulfilled the 1982 American College of Rheumatology SLE classification criteria. Antiphospholipid syndrome–related events were obtained from patients’ records. IgA/G/M anticardiolipin and anti-β2 glycoprotein I (β2GPI) were analysed with two independent assays. IgA anti-β2GPI domain 1 (D1) was also investigated. Manufacturers’ cut-offs and the 95th and 99th percentile cut-offs based on national controls were used. Results Sudanese patients and controls had higher levels and were more often positive for IgA aPL than Swedes when using manufacturers’ cut-offs. In contrast, using national cut-offs, the increase in IgA aPL among Sudanese patients was lost. Occurrence of IgA anti-D1 did not differ between the countries. Venous thromboses were less common among Sudanese patients and did not associate with aPL. No clinical associations were observed with IgA anti-β2GPI in Sudanese patients. Thromboses in Swedes were associated with IgG/M aPL. Fetal loss was associated with aPL in both cohorts. Conclusions IgA anti-β2GPI prevalence was higher among Sudanese compared to Swedish patients when manufacturers’ cut-offs were used. This situation was reversed when applying national cut-offs. Anti-D1 was not increased in Sudanese patients. Previous studies on populations of African origin, which demonstrate a high prevalence of IgA aPL positivity, should be re-evaluated using a similar cut-off approach.

scholarly journals Genetic variations in A20 DUB domain provide a genetic link to citrullination and neutrophil extracellular traps in systemic lupus erythematosus

2019 ◽  
Vol 78 (10) ◽  
pp. 1363-1370 ◽  
Author(s):  
Lina Odqvist ◽  
Zala Jevnikar ◽  
Rebecca Riise ◽  
Lisa Öberg ◽  
Magdalena Rhedin ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune Cells ◽  
Lupus Erythematosus ◽  
Genetic Alterations ◽  
Genetic Variations ◽  
Negative Regulator ◽  
Systemic Lupus ◽  
Trap Formation ◽  
Autoimmune Pathology ◽  
Extracellular Trap

ObjectivesGenetic variations in TNFAIP3 (A20) de-ubiquitinase (DUB) domain increase the risk of systemic lupus erythematosus (SLE) and rheumatoid arthritis. A20 is a negative regulator of NF-κB but the role of its DUB domain and related genetic variants remain unclear. We aimed to study the functional effects of A20 DUB-domain alterations in immune cells and understand its link to SLE pathogenesis.MethodsCRISPR/Cas9 was used to generate human U937 monocytes with A20 DUB-inactivating C103A knock-in (KI) mutation. Whole genome RNA-sequencing was used to identify differentially expressed genes between WT and C103A KI cells. Functional studies were performed in A20 C103A U937 cells and in immune cells from A20 C103A mice and genotyped healthy individuals with A20 DUB polymorphism rs2230926. Neutrophil extracellular trap (NET) formation was addressed ex vivo in neutrophils from A20 C103A mice and SLE-patients with rs2230926.ResultsGenetic disruption of A20 DUB domain in human and murine myeloid cells did not give rise to enhanced NF-κB signalling. Instead, cells with C103A mutation or rs2230926 polymorphism presented an upregulated expression of PADI4, an enzyme regulating protein citrullination and NET formation, two key mechanisms in autoimmune pathology. A20 C103A cells exhibited enhanced protein citrullination and extracellular trap formation, which could be suppressed by selective PAD4 inhibition. Moreover, SLE-patients with rs2230926 showed increased NETs and increased frequency of autoantibodies to citrullinated epitopes.ConclusionsWe propose that genetic alterations disrupting the A20 DUB domain mediate increased susceptibility to SLE through the upregulation of PADI4 with resultant protein citrullination and extracellular trap formation.

scholarly journals Multiple Functions of B Cells in the Pathogenesis of Systemic Lupus Erythematosus

2019 ◽  
Vol 20 (23) ◽  
pp. 6021 ◽  
Author(s):  
Kongyang Ma ◽  
Wenhan Du ◽  
Xiaohui Wang ◽  
Shiwen Yuan ◽  
Xiaoyan Cai ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Therapeutic Interventions ◽  
Systemic Lupus ◽  
Autoantibody Production ◽  
Regulatory B Cell ◽  
Functional Features ◽  
B Cell Subsets

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by excessive autoantibody production and multi-organ involvement. Although the etiology of SLE still remains unclear, recent studies have characterized several pathogenic B cell subsets and regulatory B cell subsets involved in the pathogenesis of SLE. Among pathogenic B cell subsets, age-associated B cells (ABCs) are a newly identified subset of autoreactive B cells with T-bet-dependent transcriptional programs and unique functional features in SLE. Accumulation of T-bet+ CD11c+ ABCs has been observed in SLE patients and lupus mouse models. In addition, innate-like B cells with the autoreactive B cell receptor (BCR) expression and long-lived plasma cells with persistent autoantibody production contribute to the development of SLE. Moreover, several regulatory B cell subsets with immune suppressive functions have been identified, while the impaired inhibitory effects of regulatory B cells have been indicated in SLE. Thus, further elucidation on the functional features of B cell subsets will provide new insights in understanding lupus pathogenesis and lead to novel therapeutic interventions in the treatment of SLE.

scholarly journals Analysis of autoantibody production in SCID-systemic lupus erythematosus (SLE) chimeras

2008 ◽  
Vol 88 (1) ◽  
pp. 84-90 ◽  
Author(s):  
D. ASHANY ◽  
J. HINES ◽  
A. GHARAVI ◽  
J. MOURADIAN ◽  
K. B. ELKON
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Autoantibody Production
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