Pathophysiology Of Systemic Lupus Erythematosus Research Articles

Linfócitos Th17 e linfócitos T CD4+ multifuncionais em pacientes com lúpus eritematoso sistêmico

Introduction/ObjectiveRecent evidence suggests that abnormalities involving Th17 lymphocytes are associated with the pathophysiology of systemic lupus erythematosus (SLE). In addition, multifunctional T cells (MFT), i. e., those producing multiple cytokines simultaneously, are present in the inflammatory milieu and may be implicated in the autoimmune process observed in SLE. In the present study, we aimed to characterize the functional status of CD4+ T cells in SLE by simultaneously determining the concentration of IL‐2, IFN‐γ and IL‐17 in lymphocyte cultures under exogenous and self‐antigenic stimuli. Patients and methodsEighteen patients with active disease, 18 with inactive disease, and 14 healthy controls had functional status of CD4+ T cells analyzed. ResultsWe found that SLE patients presented a decreased number of total CD4+ cells, an increased number of activated T cells, and an increased frequency of Th17 cells compared to healthy controls (HC). MFT cells had increased frequency in SLE patients and there was an increased frequency of tri‐functional MFT in patients with active SLE compared with those with inactive SLE. Interestingly, MTF cells produced larger amounts of IFNγ than mono‐functional T cells in patients and controls. ConclusionTaken together these data indicate the participation of recently activated Th17 cells and MTF cells in the SLE pathophysiology.

Reproductive Health Concerns in Women with Systemic Lupus Erythematosus.

Women are far more likely than men to have a diagnosis of systemic lupus erythematosus (SLE), with a peak incidence during the childbearing years. Contraceptive methods and pregnancy can both adversely affect the health of women with SLE, thus careful planning and interventions are necessary to help women manage their reproductive health choices. Women with SLE may experience infertility, difficulties conceiving and maintaining pregnancy, and ultimately have less children than they had planned. Although poor health status may account for some of this disparity, inadequate counseling and management by members of the healthcare team may also be responsible. The purpose of this article is to review the pathophysiology of SLE and its effects on reproductive health, as well as to highlight recent literature supporting evidence-based practices in reproductive health counseling, nursing care during pregnancy, and monitoring for disease complications in women with SLE. Nurses play a central role in care coordination and patient education for women with SLE making decisions about family planning.

Analysis of CD95 and CCR7 expression on circulating CD4+ lymphocytes revealed disparate immunoregulatory potentials in systemic lupus erythematosus

Emerging data have implicated a critical role for CD4 in the pathogenesis of systemic lupus erythematosus (SLE). This study was designed to delineate the contribution of CD4+ T cells in the pathogenesis of SLE disease. Forty-four patients (3 male: 41 female) and 20 healthy volunteers (4 male: 16 female) were included in the study. CD4+ lymphocytes analysis was done using three-color flow cytometry with antibodies against human-CD95, a prototype cell death receptor, and the chemokine receptor-7 (CCR7) after gating for lymphocytes based on the forward and side scatter. Serum levels of IL-6, IL-12, IL-17, TNF-α and IL-10 cytokines were assayed using ELISA. Disease activity was assessed using the SLE disease activity index (SLEDAI). Based on the expression of CCR7 and CD95, CD4+ lymphocytes were subdivided into three particular subsets; CD4+CD95+CCR7+ cells, CD4+CD95−CCR7+ cells and CD4+CD95+CCR7− cells. Percentage of CD4+CD95+CCR7+ cell subset was significantly higher in patients with SLE with active disease (SLEDAI>6) and inactive (SLEDAI<6) as compared with controls (P=0.005), and it showed a significant positive correlation with ANA titer (P=0.01), and a negative correlation with WBCs count (P=0.001). CD4+CD95+CCR7− cell subset was significantly higher in active SLE patients in comparison to patients with inactive disease and controls (P=0.05, P=0.005 respectively), and it correlates positively with SLEDAI, IL-6 and IL-17 levels (P=0.001, 0.05, 0.01 respectively), and negatively with blood WBCs counts (P=0.001). The third CD4+CD95−CCR7+cell subset was found significantly lower in SLE patients compared with controls, and it was found negatively correlated with IL-10, IL-6, and IL-17. The results show that CD4+CD95+subset lacking expression of CCR7 is associated with cell mediated inflammatory response as manifested by its correlation with signs of inflammation, inflammatory cytokines and disease activity index. Whereas, CD4+CD95+CCR7+ correlate more with antibody immune responses as manifested by association with serum ANA. These data suggest disparate roles of these cell subsets in the pathophysiology of SLE. A better understanding of the characteristics of CD4 cell subsets may shed light on the pathogenesis of autoimmune diseases, particularly SLE.

T cell signaling abnormalities contribute to aberrant immune cell function and autoimmunity.

Systemic lupus erythematosus (SLE) is a prototype systemic autoimmune disease that results from a break in immune tolerance to self-antigens, leading to multi-organ destruction. Autoantibody deposition and inflammatory cell infiltration in target organs such as kidneys and brain lead to complications of this disease. Dysregulation of cellular and humoral immune response elements, along with organ-defined molecular aberrations, form the basis of SLE pathogenesis. Aberrant T lymphocyte activation due to signaling abnormalities, linked to defective gene transcription and altered cytokine production, are important contributors to SLE pathophysiology. A better understanding of signaling and gene regulation defects in SLE T cells will lead to the identification of specific novel molecular targets and predictive biomarkers for therapy.

Guanine-Modified Inhibitory Oligonucleotides Efficiently Impair TLR7- and TLR9-Mediated Immune Responses of Human Immune Cells

Activation of TLR7 and TLR9 by endogenous RNA- or DNA-containing ligands, respectively, is thought to contribute to the complicated pathophysiology of systemic lupus erythematosus (SLE). These ligands induce the release of type-I interferons by plasmacytoid dendritic cells and autoreactive antibodies by B-cells, both responses being key events in perpetuating SLE. We recently described the development of inhibitory oligonucleotides (INH-ODN), which are characterized by a phosphorothioate backbone, a CC(T)XXX3–5GGG motif and a chemical modification of the G-quartet to avoid the formation of higher order structures via intermolecular G-tetrads. These INH-ODNs were equally or significantly more efficient to impair TLR7- and TLR9-stimulated murine B-cells, macrophages, conventional and plasmacytoid dendritic cells than the parent INH-ODN 2088, which lacks G-modification. Here, we evaluate the inhibitory/therapeutic potential of our set of G-modified INH-ODN on human immune cells. We report the novel finding that G-modified INH-ODNs efficiently inhibited the release of IFN-α by PBMC stimulated either with the TLR7-ligand oligoribonucleotide (ORN) 22075 or the TLR9-ligand CpG-ODN 2216. G-modification of INH-ODNs significantly improved inhibition of IL-6 release by PBMCs and purified human B-cells stimulated with the TLR7-ligand imiquimod or the TLR9-ligand CpG-ODN 2006. Furthermore, inhibition of B-cell activation analyzed by expression of activation markers and intracellular ATP content was significantly improved by G-modification. As observed with murine B-cells, high concentrations of INH-ODN 2088 but not of G-modified INH-ODNs stimulated IL-6 secretion by PBMCs in the absence of TLR-ligands thus limiting its blocking efficacy. In summary, G-modification of INH-ODNs improved their ability to impair TLR7- and TLR9-mediated signaling in those human immune cells which are considered as crucial in the pathophysiology of SLE.

Epigenetics and lupus

Systemic lupus erythematosus (SLE) is among the systemic autoimmune diseases whose complex pathogenesis involves both genetic and environmental factors. Epigenetic dysregulation resulting in overexpression of certain genes in some of the key immune cells, such as T cells, has been incriminated in the pathophysiology of SLE. Epigenetics is defined as transmissible and reversible modifications in gene expression without alterations in the nucleotide sequences. Epigenetic information is carried chiefly by DNA itself, histones, and noncoding RNAs. Several epigenetic mechanisms may play a role in SLE pathogenesis. This review discusses the various epigenetic mechanisms that regulate gene expression and provides examples relevant to SLE.

Biomarkers identified from serum proteomic analysis for the differential diagnosis of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that involves different organs. Its most important feature is the production of specific autoantibodies against nuclear or cytoplasmic antigens. Proteomic analysis of serum, as one of the most readily available body fluids, can be used as a method for clarifying the pathogenesis of SLE. In this study the serum proteome of 13 patients with SLE was evaluated and compared with seven healthy control participants. A specific kit was used to remove high-abundance proteins. After depletion, the protein expression patterns created by two-dimensional gel electrophoresis (2-DE) and MALDI-TOF/TOF-MS were used to identify disease-associated proteins. We found differential expression of 15 protein spots, including seven up-regulated and eight down-regulated proteins in SLE samples, in comparison with healthy participants. These spots were identified by MALDI-TOF/TOF-MS and classified into three groups include keratins, apolipoproteins and albumin, and individual proteins such as transthyretin, haptoglobin and prothrombin. These findings can help to clarify the pathophysiology and mechanism of SLE.

A 2014 update on the management of patients with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a chronic, relapsing autoimmune connective tissue disease, primarily affecting the skin, joints, kidneys, heart, lungs, nervous system, blood elements, and serosal membranes. SLE is characterized by cytokine dysregulation, polyclonal B-cell activation, autoantibody production, and increased immune complex formation due to aberrations involving hyperactive B cells, T cells, and cells of the monocytic lineage. The symptoms of SLE are often diverse and nonspecific, and timely identification of SLE and associated comorbidities in patients is critical as aggressive monitoring and therapy may be warranted, especially in patients with poor prognoses. Based on the up-to-date understanding of the pathophysiology of SLE, the first targeted biological agent belimumab has been approved by the US Food and Drug Administration (FDA) in more than 50 years, and many targeted agents are being evaluated in late-stage clinical trials. There is a clear need to discuss how and when to incorporate new and emerging biological agents in managing patients with SLE. Additionally, the potential for increased risk of infections is a factor that heavily influences the rheumatologist׳s decision to use biological agents in managing patients with SLE. Hence, in this roundtable educational activity, expert faculty will review and discuss the strategies for timely diagnosis of SLE and associated comorbidities. They will also discuss the current understanding of the pathophysiology of SLE and how new and emerging biological agents help address the underlying pathophysiological aberrations in patients with SLE. The faculty will also review strategies to minimize the risk of infections and other toxicities in patients with SLE.

The role of T cells in systemic lupus erythematosus: an update.

To describe our current understanding of the role of T cells in the pathophysiology of systemic lupus erythematosus (SLE). Over the last few years, the dominant role of T cells in autoimmunity and SLE was established. Genome-wide-association studies led to the discovery of multiple single-nucleotide polymorphisms associated with SLE. Most of these single-nucleotide polymorphisms fall within the noncoding DNA regions of immune response-related genes and few seem to contribute to the observed abnormal T cell function. The field of epigenetics research developed rapidly and provided us with new insights into the observed generalized hypomethylation in SLE T cells, the abnormal histone modifications and the role of RNA interference. Old observations, such as the decreased interleukin-2 production, are better understood with our evolved knowledge of many signal transduction pathways and the way they converge and regulate the transcription of different genes in T cells. Finally, we are now able to identify subpopulations of T cells, such as Th17 and T regulatory cells, and to define their role in SLE. T cells are key players in SLE, and over the last few years our understanding of their activation, signal transduction and gene regulation has evolved significantly.

Retraction: Interleukin 17 acts in synergy with B cell-activating factor to influence B cell biology and the pathophysiology of systemic lupus erythematosus.

Retraction: Interleukin 17 acts in synergy with B cell-activating factor to influence B cell biology and the pathophysiology of systemic lupus erythematosus.

Production of IgG autoantibody requires expression of activation-induced deaminase in early-developing B cells in a mouse model of SLE.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of pathogenic IgG antinuclear antibodies. Pathogenic IgG autoantibody production requires B-cell activation, leading to the production of activation-induced deaminase (AID) and class switching of IgM genes to IgG. To understand how and when B cells are activated to produce these IgG autoantibodies, we studied cells from 564Igi, a mouse model of SLE. 564Igi mice develop a disease profile closely resembling that found in human SLE patients, including the presence of IgG antinucleic acid Abs. We have generated 564Igi mice that conditionally express an activation-induced cytidine deaminase transgene (Aicda(tg) ), either in all B cells or only in mature B cells. Here, we show that class-switched pathogenic IgG autoantibodies were produced only in 564Igi mice in which AID was functional in early-developing B cells, resulting in loss of tolerance. Furthermore, we show that the absence of AID in early-developing B cells also results in increased production of self-reactive IgM, indicating that AID, through somatic hypermutation, contributes to tolerance. Our results suggest that the pathophysiology of clinical SLE might also be dependent on AID expression in early-developing B cells.

The BAFF/APRIL system in SLE pathogenesis

Systemic lupus erythematosus (SLE) is characterized by multisystem immune-mediated injury in the setting of autoimmunity to nuclear antigens. The clinical heterogeneity of SLE, the absence of universally agreed clinical trial end points, and the paucity of validated therapeutic targets have, historically, contributed to a lack of novel treatments for SLE. However, in 2011, a therapeutic monoclonal antibody that neutralizes the cytokine TNF ligand superfamily member 13B (also known as B-cell-activating factor of the TNF family [BAFF]), belimumab, became the first targeted therapy for SLE to have efficacy in a randomized clinical trial. Because of its specificity, the efficacy of belimumab provides an opportunity to increase understanding of SLE pathophysiology. Although belimumab depletes B cells, this effect is not as powerful as that of other B-cell-directed therapies that have not been proven efficacious in randomized clinical trials. In this article, therefore, we review results suggesting that neutralizing BAFF can have effects on the immune system other than depletion of B cells. We also identify aspects of the BAFF system for which data in relation to SLE are still missing, and we suggest studies to investigate the pathogenesis of SLE and ways to refine anti-BAFF therapies. The role of a related cytokine, TNF ligand superfamily member 13 (also known as a proliferation-inducing ligand [APRIL]) in SLE is much less well understood, and hence this review focuses on BAFF.

Association of extended interleukin-10 promoter haplotypes with disease susceptibility and manifestations in German patients with systemic lupus erythematosus

Associations of interleukin-10 (IL-10) promoter single nucleotide polymorphisms (SNPs) and their haplotypes with systemic lupus erythematosus (SLE) are unclear. We extended the analysis of established proximal IL-10 promoter haplotypes to a more distal SNP with functional capacity. Two hundred and ten German caucasian SLE patients fulfilling the ACR criteria and 160 ethnically, age and sex matched controls were genotyped for IL-10 -2849 G > A, -1082 A > G, -819 T > C and -592 C > A. Haplotypes were reconstructed via a mathematical model, then allele and haplotype distributions were compared between patients and controls and patients with different disease manifestations. We detected at -2849, -1082, -819 and -592 the four predominant haplotypes GGCC (22% in patients vs. 29% in controls), AGCC (24% vs. 21%), GACC (30% vs. 25%) and GATA (24% vs. 24%). GGCC was underrepresented in SLE patients, suggesting a protective effect (odds ratio (OR) 0.67, 95% confidence interval (CI) 0.48-0.94). AGCC was found significantly more frequently in patients with pathognomonic anti-dsDNA antibodies (26% vs. 15%; OR 1.98, 95% CI 1.04-3.75). As compared to patients with glomerulonephritis type V (WHO classification), the presumptive IL-10 high producer allele -2849 G was found significantly more often in patients with GN type III/IV (93% vs. 60%; OR 8.7, 95% CI 1.59-47.15). Our data confirm that the complexity of the IL-10 promoter evokes the need for a meticulous analysis of its haplotypic structure in order to specify disease associations, particularly under functional aspects, thereby shedding light on the pathophysiology of SLE.

Plasma Annexin A5, Anti-Annexin A5 Antibodies and Annexin A5 Polymorphism in Egyptian Female Patients with Systemic Lupus Erythematosus and Antiphospholipid Syndrome

Annexin A5 exhibits anticoagulant properties that appear to be defective in patients with antiphospholipid syndrome (APS) resulting in repeated thrombosis and recurrent pregnancy loss (RPL). APS occurs frequently in association with systemic lupus erythematosus (SLE). The present study aimed to find out a possible relationship between annexin A5 (gene polymorphism, antibodies or plasma level) and the pathophysiology of SLE, APS and RPL. 47 female patients divided into 3 groups (SLE, APS and RPL) and 20 healthy controls are included in the study. Detection of annexin A5 (-1C/T) gene polymorphism was done by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) assay. Anti-annexin A5 antibodies (IgG and IgM) and annexin A5 plasma level were measured by Enzyme Linked Immunosorbent Assay (ELISA). The frequency of annexin A5 (-1C/T) polymorphism was significantly higher in SLE related groups (p = 0.02), but it did not correlate with RPL (p = 0.57) or annexin A5 level (p = 0.5). Anti-annexin A5 IgM level was significantly higher among APS patients and was associated with RPL (p = 0.005, odds ratio = 23.75, 95% confidence interval = 2.15 - 262.48). Annexin A5 (-1C/T) gene mutation may play a role in the pathophysiology of SLE. Anti-annexin A5 IgM was the antibody associated with RPL in this group of APS patients. Annexin A5 plasma levels are not affected by the presence of annexin A5 (-1C/T) polymorphism.

Combined bilateral retinal arteriolar and retinal vein occlusion: An unusual presentation of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a rare autoimmune disease associated with multi-organ damage mediated by tissue-binding autoantibodies and immune complexes. [1] Common ocular manifestations of SLE include nonspecific conjunctivitis, anterior uveitis, or iridocyclitis, which rarely threaten vision. In contrast, retinal vasculitis and optic neuritis are serious manifestations. [2] Branch retinal arteriolar occlusion (BRAO) and branch retinal vein occlusion (BRVO) in patients younger than 30 years of age is rarely caused by atheromatous diseases. Other diverse etiologies are more likely to be inflammatory and infectious conditions. Here, we have report a case of a 17-year-old woman with SLE and hypocomplementenemia, who presented with sudden loss of vision. A rare presentation of SLE is found as combined BRAO and BRVO in both the eyes (OU). Despite advances in the understanding of pathophysiology of SLE, its complications remains enigmatic and, in some instances, it may be multifactorial. Early accurate diagnosis and aggressive immunosuppression is recommended, which helps in the management and preservation of the vision.

Bruton's Tyrosine Kinase Is Required for Apoptotic Cell Uptake via Regulating the Phosphorylation and Localization of Calreticulin

In addition to regulating B cell development and activation, Bruton's tyrosine kinase (Btk) functions downstream of multiple TLRs, including TLR7, to regulate innate immune responses in myeloid cells. Although critical for defense against RNA viruses such as influenza and Sendai virus, recognition of self-RNA by TLR7 also has been shown to be an important contributor to the pathophysiology of systemic lupus erythematosus. To date, the role of Btk in regulating TLR7-mediated responses is poorly understood. In the current study, we have demonstrated a hitherto undiscovered role for Btk in apoptotic cell uptake, identifying the molecular chaperone calreticulin (CRT) as a novel substrate for Btk in regulating this response. CRT together with the transmembrane receptor CD91 function at the cell membrane and regulate uptake of C1q-opsonised apoptotic cells. Our results show that Btk directly phosphorylates CRT and that in the absence of Btk, CRT fails to localize with CD91 at the cell surface and at the phagocytic cup. Critically, a blocking Ab against CRT in wild-type macrophages mimics the inability of Btk-deficient macrophages to phagocytose apoptotic cells efficiently, indicating the critical importance of Btk in regulating CRT-driven apoptotic cell uptake. Our data have revealed a novel regulatory role for Btk in mediating apoptotic cell clearance, with CRT identified as the critical component of the CRT/CD91/C1q system targeted by Btk. Given the importance of clearing apoptotic cell debris to prevent inappropriate exposure of TLRs to endogenous ligands, our results have important implications regarding the role of Btk in myeloid cell function.

Vitamin D and systemic lupus erythematosus: an update

Vitamin D is a steroid hormone that, in addition to its actions on calcium and bone metabolism, exhibits a plethora of regulatory effects on growth, proliferation, apoptosis and function of the cells of the immune system that are relevant to the pathophysiology of systemic lupus erythematosus (SLE). Hypovitaminosis D is highly prevalent in SLE as a result of avoidance of sunshine, photoprotection, renal insufficiency and the use of medications such as glucocorticoids, anticonvulsants, antimalarials and the calcineurin inhibitors, which alter the metabolism of vitamin D or downregulate the functions of the vitamin D receptor. Low levels of vitamin D correlate with disease activity, and is associated with osteoporosis, fatigue and certain cardiovascular risk factors in SLE patients. This review updates the recent evidence on the relationship between vitamin D status and the onset, activity and complications of SLE, and summarizes the recommendations for vitamin D supplementation.

B cell biology: implications for treatment of systemic lupus erythematosus

B cells are critical players in the orchestration of properly regulated immune responses, normally providing protective immunity without autoimmunity. Balance in the B cell compartment is achieved through the finely regulated participation of multiple B cell populations with different antibody-dependent and independent functions. Both types of functions allow B cells to modulate other components of the innate and adaptive immune system. Autoantibody-independent B cell functions include antigen presentation, T cell activation and polarization, and dendritic cell modulation. Several of these functions are mediated by the ability of B cells to produce immunoregulatory cytokines and chemokines and by their critical contribution to lymphoid tissue development and organization including the development of ectopic tertiary lymphoid tissue. Additionally, the functional versatility of B cells enables them to play either protective or pathogenic roles in autoimmunity. In turn, B cell dysfunction has been critically implicated in the pathophysiology of systemic lupus erythematosus (SLE), a complex disease characterized by the production of autoantibodies and heterogeneous clinical involvement. Thus, the breakdown of B cell tolerance is a defining and early event in the disease process and may occur by multiple pathways, including alterations in factors that affect B cell activation thresholds, B cell longevity, and apoptotic cell processing. Once tolerance is broken, autoantibodies contribute to autoimmunity by multiple mechanisms including immune-complex mediated Type III hypersensitivity reactions, type II antibody-dependent cytotoxicity, and by instructing innate immune cells to produce pathogenic cytokines including IFNα, TNF and IL-1. The complexity of B cell functions has been highlighted by the variable success of B cell-targeted therapies in multiple autoimmune diseases, including those conventionally viewed as T cell-mediated conditions. Given the widespread utilization of B cell depletion therapy in autoimmune diseases and the need for new therapeutic approaches in SLE, a better understanding of human B cell subsets and the balance of pathogenic and regulatory functions is of the essence.

Plasma catecholamine metabolite levels and the activities of psychiatric symptoms in systemic lupus erythematosus

Neuropsychiatric systemic lupus erythematosus (NPSLE) is accompanied by neurological or psychiatric symptoms that can be severe. We hypothesized plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA) levels were the biological marker that reflected the severity of the NPSLE psychiatric symptoms, and we examined MHPG and HVA levels in systemic lupus erythematosus (SLE) patients. The participants were 42 healthy volunteers and 41 SLE patients. SLE patients were divided into the three groups: NPSLE with psychiatric symptoms (NP group), NPSLE without psychiatric symptoms (NN group), and SLE without neuropsychiatric symptoms (S group). All blood samples were drawn before (T0) and after 4 weeks of treatment (T4) in all SLE patients, and once in the healthy volunteers. Plasma levels of MHPG and HVA were analyzed using high-performance liquid chromatography. Plasma MHPG levels at T0 were significantly increased in the SLE compared to those in healthy volunteers. The NN group had the greatest increase compared with other SLE patient groups. There were no significant differences in plasma HVA levels at T0 between the four groups, and there was also no difference in MHPG and HVA plasma levels between T0 and T4. Hyperactivity of noradrenergic neurons and/or sympathetic nerves might be involved in SLE pathophysiology.

Leukocyte Mitochondrial DNA Alteration in Systemic Lupus Erythematosus and Its Relevance to the Susceptibility to Lupus Nephritis

The role of mitochondrial DNA (mtDNA) alterations in the pathophysiology of systemic lupus erythematosus (SLE) remains unclear. We investigated sequence variations in the D310 region and copy number change of mtDNA in 85 SLE patients and 45 normal subjects. Leukocyte DNA and RNA were extracted from leukocytes of the peripheral venous blood. The D310 sequence variations and copy number of mtDNA, and mRNA expression levels of mtDNA-encoded genes in leukocytes were determined by quantitative real-time polymerase chain reaction (Q-PCR) and PCR-based direct sequencing, respectively. We found that leukocyte mtDNA in SLE patients exhibited higher frequency of D310 heteroplasmy (69.4% vs. 48.9%, p = 0.022) and more D310 variants (2.2 vs. 1.7, p = 0.014) than those found in controls. Among normal controls and patients with low, medium or high SLE disease activity index (SLEDAI), an ever-increasing frequency of D310 heteroplasmy was observed (p = 0.021). Leukocyte mtDNA copy number tended to be low in patients of high SLEDAI group (p = 0.068), especially in those harboring mtDNA with D310 heteroplasmy (p = 0.020). Moreover, the mtDNA copy number was positively correlated with the mRNA level of mtDNA-encoded ND1 (NADH dehydrogenase subunit 1) (p = 0.041) and ATPase 6 (ATP synthase subunit 6) (p = 0.030) genes. Patients with more D310 variants were more susceptible to lupus nephritis (p = 0.035). Taken together, our findings suggest that decrease in the mtDNA copy number and increase in D310 heteroplasmy of mtDNA are related to the development and progression of SLE, and that the patients harboring more D310 variants of mtDNA are more susceptible to lupus nephritis.