人巨细胞病毒pp65对系统性红斑狼疮诱导作用的研究

目的 探究人巨细胞病毒(HCMV) pp65是否可以诱发正常C57BL/6小鼠产生系统性红斑狼疮(SLE)相关实验室诊断指标的变化.方法 构建HCMV pp65原核表达质粒与真核表达质粒,然后进行HCMV pp65原核蛋白表达与纯化.间接法ELISA检测anti-pp65 IgG、dsDNA、抗核抗体(ANA),竞争法ELISA检测血浆中IL-1b、IL-6、TNF-α浓度.结果 成功获得HCMV pp65原核表达蛋白和真核表达质粒,免疫小鼠后血清中anti-pp65、抗dsDNA抗体、ANA、IL-6均有明显上升趋势.结论 HCMVpp65可以使C57BL/6小鼠SLE相关检测指标发生明显改变,这一结果有助于进一步研究自身免疫病的发病机制与影响因素.     

Protein array autoantibody profiles for insights into systemic lupus erythematosus and incomplete lupus syndromes

The objective of this study was to investigate the prevalence and clinical significance of a spectrum of autoantibodies in systemic lupus erythematosus and incomplete lupus syndromes using a proteome microarray bearing 70 autoantigens. Microarrays containing candidate autoantigens or control proteins were printed on 16-section slides. These arrays were used to profile 93 serum samples from patients with systemic lupus erythematosus (SLE (n = 33), incomplete LE (ILE; n = 23), first-degree relatives (FDRs) of SLE patients (n = 20) and non-autoimmune controls (NC; n = 17). Data were analysed using the significance analysis of microarray (SAM) and clustering algorithms. Correlations with disease features were determined. Serum from ILE and SLE patients contained high levels of IgG autoantibodies to 50 autoantigens and IgM autoantibodies to 12 autoantigens. Elevated levels of at least one IgG autoantibody were detected in 26% of SLE and 19% of ILE samples; elevated IgM autoantibodies were present in 13% of SLE and 17% of ILE samples. IgG autoantibodies segregated into seven clusters including two specific for DNA and RNA autoantigens that were correlated with the number of lupus criteria. Three IgG autoantibody clusters specific for collagens, DNA and histones, were correlated with renal involvement. Of the four IgM autoantibody clusters, two were correlated negatively with the number of lupus criteria; none were correlated with renal disease. The IgG : IgM autoantibody ratios generally showed a stepwise increase in the groups following disease burden from NC to SLE. Insights derived from the expanded autoantibody profiling made possible with the antigen array suggest differences in autoreactivity in ILE and SLE. Determining whether the IgM aurotreactivity that predominates in ILE represents an early stage prior to IgG switching or is persistent and relatively protective will require further longitudinal studies.     

Anti‐dsDNA antibodies as a classification criterion and a diagnostic marker for systemic lupus erythematosus: critical remarks

Antibodies to mammalian dsDNA have, for decades, been linked to systemic lupus erythematosus (SLE) and particularly to its most serious complication, lupus nephritis. This canonical view derives from studies on its strong association with disease. The dogma was particularly settled when the antibody was included in the classification criteria for SLE that developed during the 1970s, most prominently in the 1982 American College of Rheumatology (ACR), and recently in The Systemic Lupus International Collaborating Clinics (SLICC) classification criteria. There are several problems to be discussed before the anti‐dsDNA antibody can be accepted without further distinction as a criterion to classify SLE. Old and contemporary knowledge make it clear that an anti‐dsDNA antibody is not a unifying term. It embraces antibodies with a wide spectrum of fine molecular specificities, antibodies that are produced transiently in context of infections and persistently in the context of true autoimmunity, and also includes anti‐dsDNA antibodies that have the potential to bind chromatin (accessible DNA structures) and not (specificity for DNA structures that are embedded in chromatin and therefore unaccessible for the antibodies). This critical review summarizes this knowledge and questions whether or not an anti‐dsDNA antibody, as simply that, can be used to classify SLE.     

Three T-cell epitopes within the C-terminal 265 amino acids of the matrix protein pp65 of human cytomegalovirus recognized by human lymphocytes

Although a T-cell response in human cytomegalovirus (HCMV)-immune individuals exists against the most abundantly expressed protein pp65 of the virus matrix, less is known about the determinants that evoke this response. The aim of the study was to identify regions within HCMV pp65 (ppUL83) that contain sequences for the cellular immune response by the use of three recombinant overlapping β-galactosidase pp65 fusion proteins (C74, C35, and C47), covering the C-terminal 265 amino acids of the entire pp65 sequence. Two T-cell epitope determinants were recognized by human lymphocytes of healthy, HCMV-seropositive, human leukocyte antigen (HLA)-typed individuals. One T-cell determinant (amino acids [aa] 303–388) was localized in the mid-region of the entire pp65 sequence and a second T-cell determinant (aa 477–561) within the C-terminal region. By fine mapping with synthetic hexadecamer peptides three T-cell epitopes were identified within these two regions: P10-I (aa 361–376) in the mid-region, P3-II (aa) 485–499), and P6-II (aa 509–524) in the C-terminal region. Inhibition studies with monoclonal antibodies to HLA class I or class II revealed a class I restricted response to peptides P10-I or P6-II, respectively. P10-I responders shared the HLA-DR11 allele and P6-II responders the -DR3 allele. Therefore, these T-cell epitopes of HCMV pp65 might be presented in association with particular HLA class II alleles. J. Med. Virol. 52:68–76, 1997. © 1997 Wiley-Liss, Inc.     

The treatment of systemic lupus erythematosus (SLE) in NZB/W F1 hybrid mice; studies with recombinant murine DNase and with dexamethasone

The effects of recombinant mouse DNase on a well established murine model of spontaneous SLE have been evaluated. Daily intraperitoneal injections of DNase were given to female NZB/NZW F₁ mice during the period of disease development from 4 to 7 months of age or at the height of disease activity from the age of 7 months for 3 weeks. This treatment was compared with the injections of diluent and with an immunosuppressive dose of dexamethasone. The effects of treatment were evaluated using the immunological parameters of disease activity (antinucleoprotein antibody, immune complexes, serum immunoglobulins, anti-cardiolipin antibodies), proteinuria, serum creatinine and renal histopathology (light microscopy, immunofluorescence and electron microscopy). The dose of dexamethasone used (1 mg/kg per day from the age of 4 months) was sufficient to suppress the development of lupus entirely. Treatment with DNase starting at the age of 4 months postponed the development of the disease by about 1 month and extended the period from the onset of disease to death by about 30%. Mice treated for 3 weeks during the most active phase of the disease at 7 months of age showed more dramatic effects. Proteinuria and serum creatinine were significantly reduced and renal histopathology was strikingly less severe than in the control group. Immune complexes involving DNA-containing antigens are believed to play a crucial role in the pathogenesis of SLE. DNA-nucleoprotein, even in immune complexes, can be destroyed by DNase. This enzyme therefore provides a rational way to interfere with the disease process. The results reported here encourage a trial of recombinant human DNase in human SLE and lupus nephritis.     

Analysis of natural and disease-associated autoantibody repertoires: anti-endothelial cell IgG autoantibody activity in the serum of healthy individuals and patients with systemic lupus erythematosus

The present study demonstrates that natural IgG with anti-endothelialcell activity is present in the serum of healthy individualsand in pooled normal human Ig. By using a novel method thatallows for the simultaneous and quantitative assessment of reactivitiesof antibodies with a large number of antigens in tissues, weobserved that natural anti-endothelial cell antibody (AECA)recognizes a restricted set of self antigens in endothelialcells that is conserved among healthy individuals. The extentto which natural AECA activity is expressed in serum and thepattern of reactivity of AECA with endothelial cell antigensshowed little variability between individuals. Analysis of AECAin the serum of patients with systemic lupus erythematosus (SLE)revealed a higher amount of activity and a wider spectrum ofantigentic specificities than that recognized by natural antibodiesin endothelial cell extracts. AECA activity of IgG in wholeserum was lower than that of purified IgG in the case of healthyindividuals and showed little variation among individuals. incontrast, no difference was found between AECA activity of purifiedIgG and that of IgG in patients' serum, suggesting that SLEsera lack the factors that control expression of AECA activityin the serum of healthy individuals. Our results indicate thatnatural autoantibodies recognize a restricted and conservedset of self antigens. Our observations further suggest thatdefective regulation of the expressed autoreactive B cell repertoireis the basis for expansion of novel clonal specificities andenhanced autoantibody activity in serum of patients with autoimmunedisease.     

Autologous tolerogenic dendritic cells derived from monocytes of systemic lupus erythematosus patients and healthy donors show a stable and immunosuppressive phenotype

Systemic lupus erythematosus (SLE) is an autoimmune disease with unrestrained T‐cell and B‐cell activity towards self‐antigens. Evidence shows that apoptotic cells (ApoCells) trigger an autoreactive response against nuclear antigens in susceptible individuals. In this study, we focus on generating and characterizing tolerogenic dendritic cells (tolDCs) to restore tolerance to ApoCells. Monocyte‐derived dendritic cells (DCs) from healthy controls and patients with SLE were treated with dexamethasone and rosiglitazone to induce tolDCs. Autologous apoptotic lymphocytes generated by UV irradiation were given to tolDCs as a source of self‐antigens. Lipopolysaccharide (LPS) was used as a maturation stimulus to induce the expression of co‐stimulatory molecules and secretion of cytokines. TolDCs generated from patients with SLE showed a reduced expression of co‐stimulatory molecules after LPS stimulation compared with mature DCs. The same phenomenon was observed in tolDCs treated with ApoCells and LPS. In addition, ApoCell‐loaded tolDCs stimulated with LPS secreted lower levels of interleukin‐6 (IL‐6) and IL‐12p70 than mature DCs without differences in IL‐10 secretion. The functionality of tolDCs was assessed by their capacity to prime allogeneic T cells. TolDCs displayed suppressor properties as demonstrated by a significantly reduced capacity to induce allogeneic T‐cell proliferation and activation. ApoCell‐loaded tolDCs generated from SLE monocytes have a stable immature/tolerogenic phenotype that can modulate CD4⁺ T‐cell activation. These properties make them suitable for an antigen‐specific immunotherapy for SLE.     

C1q deposits at the dermoepidermal junction: A marker discriminating for discoid and systemic lupus erythematosus

Discoid lupus (DL) and systemic lupus erythematosus (SLE) patients have been comparatively evaluated for complement and immunoglobulin deposits at the dermoepidermal junction (DEJ) by immunofluorescence (IF). When IF was positive, C1q deposits were quasi-constantly found in SLE patients with or without skin lesions (90%), while C1q was found in only 29% of the DL patients. Of the 42 DL patients followed-up for at least 2 years, 4 have eventually evolved a systemic disease. In these 4, neither cryoglobulinemia nor significant titers of ANA had been found at the time of presentation. Only 1 of these 4 patients had initially circulating immune complexes (P.E.G.) and a positive IF in a normal sunprotected area. C1q deposits at the DEJ were present in all these 4. Of the remaining 38 DL patients, none has progressed to SLE: 8 had had significant titers of ANA, 5 had had circulating immune complexes, and 3 others had had cryoglobulinemia. Thus C1q deposits in DL cases are associated with a relatively high incidence of eventual systemic disease. Taken together, these data suggest that C1q deposits in skin may be a marker for systemic lupus.     

系统性红斑狼疮患者新的内源性逆转录病毒 NP9基因表达及其蛋白功能预测

目的研究新发现的人内源性逆转录病毒 NP9基因在系统性红斑狼疮(systemic lupus erythematosus, SLE)患者体内表达及其蛋白功能预测.方法逆转录PCR、T-A克隆技术和DNA序列测定分离、克隆和分析 NP9基因, 检测40例SLE患者和48名正常对照的 NP9基因表达, 借助NCBI BLAST系列分析工具及相应的基因分析软件预测其蛋白功能.结果 SLE患者组逆转录病毒 NP9基因表达阳性率为77.5%(31/40),明显高于正常对照的8.3%(4/48), P<0.01. NP9基因编码产物由74个氨基酸组成,含有多个细胞核内分布信号,其等电点(pI)为9.59,与SLE患者体内高表达的某些细胞因子具有较高同源性.结论 SLE患者存在逆转录病毒 NP9基因特异性转录, NP9表达可能与SLE发生发展相关.     

Peptides based on the complementarity-determining regions of a pathogenic autoantibody mitigate lupus manifestations of (NZB x NZW)F1 mice via active suppression

Two peptides based on the complementarity-determining regions (CDR) 1 and 3 (pCDR1 and pCDR3) of a murine monoclonal anti-DNA autoantibody that expresses the common idiotype 16/6Id were shown to down-regulate systemic lupus erythematosus (SLE)-associated T cell responses and to prevent the development of clinical symptoms in the SLE-prone mice, (NZB x NZW)F(1). In the present study the ability of the CDR-based peptides to treat an already established disease was tested. Mice were given 10 weekly injections of peptides either i.v. or s.c. The treatment led to a moderate reduction in the anti-DNA autoantibody titer, and a significant decrease in proteinuria and kidney pathology. The CDR-based peptides affected the pathogenic isotypes (IgG2a and IgG3) of the anti-DNA antibodies in the serum and in immune complexes in the kidneys. Both peptides mitigated disease manifestations and prolonged the survival of mice that were treated starting at the age of 7 months when full-blown disease was already developed. Furthermore, some beneficial effects of treatment with the CDR-based peptides could be adoptively transferred to diseased recipients. A reduction in the secretion of IL-2, IFN-gamma, IL-4 and IL-10 was detected in supernatants of splenocytes of the treated mice. In contrast, treatment up-regulated the immunosuppresive cytokine-transforming growth factor-beta. Thus the ameliorating effect of the CDR-based peptides on SLE manifestations is at least partially via the immunomodulation of the cytokine profile.     

Soluble human CD83 ameliorates lupus in NZB/W F1 mice

In the present study we explored the immunomodulatory potential of prokaryotically expressed soluble CD83 in the treatment of murine lupus using the NZB/W F1 mouse model. Therefore female NZB/W F1 lupus mice were treated either with sCD83 or PBS for 4 weeks. sCD83 treated mice showed a significantly delayed onset of anti-dsDNA autoantibody production when compared with the control group. Importantly, during the treatment period with sCD83 none of the mice showed elevated levels of anti-dsDNA autoantibodies. In addition, NZB/W F1 mice which received sCD83 displayed lower concentrations of anti-histone IgG autoantibodies. Furthermore, there was no difference in total IgG antibodies, indicating a modulatory role for sCD83 in the production of self-reactive antibodies without decreasing total IgG. These results indicate that administration of sCD83 has profound immune-modulatory effects on the induction of autoantibodies in NZB/W F1 lupus mice and may thus be a promising approach to interfere with autoimmunity in SLE and other autoantibody-driven diseases.     

Anti-5S RNA/protein (RNP) antibody levels correlate with disease activity in a patient with systemic lupus erythematosus (SLE) nephritis.

A patient with systemic lupus erythematosus (SLE) and nephritis without antibodies to dsDNA but with antibodies to a 5S RNA/protein (RNP) complex is presented. Combined RNA precipitation and Western blotting experiments strongly suggested that these newly identified autoantibodies recognized a distinct epitope on the L5 ribosomal protein of the L5/5S RNP complex first described by Steitz et al. [1]. Quantification of the anti-5S RNP antibody levels was done by hybridizing Northern blots of immunoprecipitated RNA from serial serum samples with a 32P-labelled oligoprobe specific for the 5S ribosomal RNA. These studies revealed a strong association between anti-5S RNP autoantibody titre and severity of SLE nephritis over a 3-year prospective study. Our results indicate that the L5/5S RNP can be a target of autoimmune response, and and may serve, in some cases, as marker of SLE severity and response to therapy.     

Lupus lymphadenitis simulating Kikuchi's lymphadenitis in patients with systemic lupus erythematosus: a clinicopathological analysis of six cases and review of the literature

Kikuchi's disease (KD) or Kikuchi's lymphadenitis (KL) is a self-limiting disease mostly affecting the cervical lymph nodes of young individuals. Whether the reported cases of KL associated with systemic lupus erythematosus (SLE) were genuine KL or lupus lymphadenitis (LL) simulating KL in SLE patients is not clear. We analyzed six cases of KD-like lymphadenitis occurring in SLE patients and 12 reported cases to clarify the relationship between KL and SLE. We found that not all cases occurred simultaneously with SLE. Eight cases occurred either before or after SLE. These cases might have true KL independent of SLE with the exception of two cases that occurred after SLE, but the patients still had lupus activity. The 10 cases that coexisted with SLE most likely had LL rather than KL. This was supported by the immunohistochemical finding of sparse cytotoxic T cells in those lymph nodes in contrast to abundant cytotoxic T cells usually seen in a typical KL. We conclude that KL is not related to SLE, and KD-like lymphadenitis coexisting with SLE should be regarded as LL. Pathologists should be aware of the possibility that LL can mimic KL in patients with SLE, especially necrotizing-type KL.     

Cloning and nucleotide sequence of cDNA for Ki antigen, a highly conserved nuclear protein detected with sera from patients with systemic lupus erythematosus.

Patients with systemic lupus erythematosus (SLE) produce autoantibodies against a variety of nuclear antigens including Ki antigen. Although anti-Ki autoantibodies were found in a significant number of SLE patients, the nature of Ki antigen is poorly characterized. By using anti-Ki serum as a probe we have cloned a bovine cDNA directing the synthesis in Escherichia coli of a polypeptide immunologically indistinguishable from the authentic Ki antigen. A homologous human cDNA was also cloned and its nucleotide sequence predicted the entire primary structure of a novel nuclear protein with a molecular weight of 29 508 and with highly hydrophilic and weakly acidic character. The gene is highly conserved not only in the coding region but also in the 3'-untranslated region. The bacterially produced Ki antigen would be valuable for diagnosis of SLE.     

Detection of a circulating form of vascular cell adhesion molecule-1: raised levels in rheumatoid arthritis and systemic lupus erythematosus.

We have developed a panel of MoAbs against four separate but overlapping epitopes on endothelial cell (EC) vascular cell adhesion molecule-1 (VCAM-1). Two of the MoAbs (1G11 and 1E5) inhibited T cell adhesion to tumour necrosis factor (TNF)-activated EC, whilst two MoAbs (1.4C3 and 6D9) did not. Using these MoAbs we have identified a circulating form of VCAM-1 (cVCAM-1) which has identical epitope distribution to the EC form, and which is able to support the adhesion of the human lymphoblastoid cell line Jurkat J6 by a VLA-4- and VCAM-1-dependent mechanism when immobilized from plasma. cVCAM-1 isolated by immunoaffinity and size-exclusion chromatographies was shown by SDS-PAGE to have an apparent mol. wt of 85-90 kD. Levels of cVCAM-1 were significantly raised (P < 0.001) in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) compared with normal individuals. It is possible that cVCAM-1 may be a useful plasma marker for the diagnosis and management of patients with inflammatory diseases. Furthermore, detection of elevated cVCAM-1 levels may act as a guide to the importance of VCAM-1-dependent cell adhesion in different pathological settings.     

Levels of soluble VCAM-1, soluble ICAM-1, and soluble E-selectin during disease exacerbations in patients with systemic lupus erythematosus (SLE); a long term prospective study.

Active SLE is characterized by immune deposits and subsequent vascular inflammation in many organs. Expression and up-regulation of adhesion molecules is basic to migration of inflammatory cells into the tissues. Recently, soluble isoforms of these molecules have been described which might be an expression of their up-regulation in the tissues and, as such, of disease activity. The purpose of this study was to evaluate whether changes in levels of soluble adhesion molecules reflect disease activity. We analysed serial sera in a 6-month period preceding 22 consecutive exacerbations of SLE for levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), and sE-selectin. Levels were related to clinical disease activity (SLEDAI), and levels of anti-dsDNA and complement. At the time of maximal disease activity, levels of sVCAM-1 in patients with SLE were higher than those in controls (P < 0.0001), levels in patients with renal involvement being higher than in those without (P < 0.02). Levels of sVCAM-1 correlated with SLEDAI scores (P < 0.05) and, inversely, with levels of C3 (P = 0.01). In addition, in the presence of anti-dsDNA, levels of sVCAM-1 tended to correlate with levels of these autoantibodies (P < 0.1). Levels of sICAM-1 were normal and sE-selectin levels even decreased compared with controls. Levels of sVCAM-1 were higher at the moment of relapse (P = 0.001) than at 6 months before this time point. This rise correlated with the rise in SLEDAI score (P < 0.02). Levels of sICAM-1 and sE-selectin did not rise, and remained in the normal range in all exacerbations studied. In conclusion, in contrast to sICAM-1 and sE-selectin, levels of sVCAM-1 are increased, rise parallel to disease activity during exacerbations in SLE, and are associated with decreasing levels of complement factors. This favours the hypothesis of immune deposit formation, activation of the complement cascade and activation of endothelial cells. Concurrent up-regulation of vascular adhesion molecules may thus result in transmigration of activated inflammatory cells inducing tissue damage.     

Multiplex family-based study in systemic lupus erythematosus: association between the R620W polymorphism of PTPN22 and the FcgammaRIIa (CD32A) R131 allele

A functional polymorphism in PTPN22, a gene encoding a phosphatase involved in T-cell signaling, has been associated with autoimmunity. We checked for the prevalence of the PTPN22 R620W polymorphism in multiplex families affected with systemic lupus erythematosus (SLE) and other autoimmune diseases. Its association with other polymorphisms in mannose binding lectin (MBL) and FcgammaRIIa (CD32A) genes was also studied. Deoxyribonucleic acid samples were obtained from 233 Spanish individuals who belonged to 21 families in which at least two members had been diagnosed with some autoimmune disease, mainly SLE. A healthy control population was also included (n= 129). Genotyping for the R620W single-nucleotide polymorphism (SNP) was performed by restriction fragment length polymorphism analysis of polymerase chain reaction products. Allele frequency for the T allele was slightly higher in the families with autoimmune disease, especially when considering the affected individuals (0.094 vs 0.062). Actually, 18.8% affected family members vs 11.6% controls had the polymorphism (P= 0.179). Nineteen percent of affected individuals had both the PTPN22 T and the CD32A R131 alleles, whereas only 8.5% unaffected relatives had both susceptibility alleles simultaneously [P= 0.031, odds ratios 2.508 (95% confidence interval 1.066-5.896)]. The tendency toward finding the T allele more frequently in members affected with some particular autoimmune disorder suggests that this SNP may confer susceptibility to autoimmunity. The fact that more affected than unaffected relatives carried both the T and the R131 alleles simultaneously leads us to think about the existence of a combinatorial effect between genes that could help define individuals prone to autoimmune diseases.     

Nucleic acid sensing receptors in systemic lupus erythematosus: development of novel DNA- and/or RNA-like analogues for treating lupus

Double‐stranded (ds) DNA, DNA‐ or RNA‐associated nucleoproteins are the primary autoimmune targets in SLE, yet their relative inability to trigger similar autoimmune responses in experimental animals has fascinated scientists for decades. While many cellular proteins bind non‐specifically negatively charged nucleic acids, it was discovered only recently that several intracellular proteins are involved directly in innate recognition of exogenous DNA or RNA, or cytosol‐residing DNA or RNA viruses. Thus, endosomal Toll‐like receptors (TLR) mediate responses to double‐stranded RNA (TLR‐3), single‐stranded RNA (TLR‐7/8) or unmethylated bacterial cytosine (phosphodiester) guanine (CpG)‐DNA (TLR‐9), while DNA‐dependent activator of IRFs/Z‐DNA binding protein 1 (DAI/ZBP1), haematopoietic IFN‐inducible nuclear protein‐200 (p202), absent in melanoma 2 (AIM2), RNA polymerase III, retinoic acid‐inducible gene‐I (RIG‐I) and melanoma differentiation‐associated gene 5 (MDA5) mediate responses to cytosolic dsDNA or dsRNA, respectively. TLR‐induced responses are more robust than those induced by cytosolic DNA‐ or RNA‐ sensors, the later usually being limited to interferon regulatory factor 3 (IRF3)‐dependent type I interferon (IFN) induction and nuclear factor (NF)‐κB activation. Interestingly, AIM2 is not capable of inducing type I IFN, but rather plays a role in caspase I activation. DNA‐ or RNA‐like synthetic inhibitory oligonucleotides (INH‐ODN) have been developed that antagonize TLR‐7‐ and/or TLR‐9‐induced activation in autoimmune B cells and in type I IFN‐producing dendritic cells at low nanomolar concentrations. It is not known whether these INH‐ODNs have any agonistic or antagonistic effects on cytosolic DNA or RNA sensors. While this remains to be determined in the future, in vivo studies have already shown their potential for preventing spontaneous lupus in various animal models of lupus. Several groups are exploring the possibility of translating these INH‐ODNs into human therapeutics for treating SLE and bacterial DNA‐induced sepsis.