Development Of Antinuclear Antibodies Research Articles

The Expression Levels of TREX1 and IFN-α Are Associated with Immune Reconstitution in HIV-1-Infected Individuals.

TREX1 acts in the initial prevention of an autoimmune response, but it may contribute to the permissiveness of retrovirus infections. This study investigated the association between the levels of TREX1 gene expression with the polymorphisms TREX1 rs3135941 (T/C) and TREX1 rs3135945 (G/A), and the presence of antinuclear antibodies (ANA) in antiretroviral therapy (ART)-naïve individuals and after 1 year of treatment. Blood samples from 119 individuals with HIV-1 were subjected to genotyping of polymorphisms and quantification of TREX1 gene expression and HIV-1 viral load by qPCR. The concentration of IFN-α and the number of CD4+/CD8+ T lymphocytes were determined by ELISA and flow cytometry, respectively; ANA was investigated by immunofluorescence. A control group of 167 seronegative individuals was used for the comparison of genotypic frequencies. The frequency of the polymorphisms were not associated with HIV infection or with variations in the expression of TREX1 and IFN-α (p > 0.05). ART-naïve individuals exhibited higher TREX1 expression and lower IFN-α expression. After 1 year of ART, TREX1 levels were reduced, while IFN-α and CD4+ T lymphocytes were elevated (p < 0.05). Some individuals on ART presented ANA. These results suggest that ART-mediated restoration of immune competence is associated with a reduction in TREX1 expression, which may induce the development of ANA, regardless of the polymorphism investigated.

Significane of determining antinuclear antibodies in systemic connective tissue disorders in children

Systemic connective tissue diseases (SCTD) are characterized by systemic autoimmune inflammation and are accompanied by development of antinuclear antibodies (ANA). Our aim was a comparative analysis of ANA in blood serum in children with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). The study included 50 patients with SLE, 50 patients with RA who were treated at the National Medical Research Center of Childrens Health. Median age was 12,2 y. o. (9-15.5). The titers of ANA and the cell fluorescence type were determined with the indirect immunofluorescence reaction (IFR) using the HEp-2 cell line (Immco Diagnostics, Inc, USA), as well as the concentration of antibodies to double-stranded DNA (adsDNA) in blood serum samples of the children detected by immunochemiluminescence (ICM) woth Elia dsDNA (Thermo Fisher Scientific, USA). A positive ANA titer and adsDNA were found, respectively, in 98% and in 48% in children with SLE. A positive ANA titer and adsDNA was detected in 100% and in 4% of children with RA, respectively. Highly positive ANA titers ( 1/1280) have been detected in 68% of children with SLE, and in 30% of children with RA. None of the RA patients with highly positive ANA titers had adsDNA. But, in patients with SLE, highly positive ANA titers and a positive dsDNA level were simultaneously detected in 16% of cases. There are both single types of cell fluorescence and their combinations in children with SLE and RA. Nuclear dot-like fluorescence was more common in children with SLE, cytoplasmic type, in children with RA, nucleolar type of glow was found only in children with RA. The revealed combinations of ANA and adsDNA titers in children with SLE and RA confirm the need for simultaneous use of RNIF and ICM.

Mild-to-moderate COVID-19 does not predispose to the development of autoimmune rheumatic diseases or autoimmune-based thrombosis.

An infection with severe acute respiratory syndrome coronavirus (SARS-CoV-2) may have a significant impact on the human immune system. Interactions between the virus and defence mechanisms may promote the development of autoimmune processes which manifest as antinuclear antibody (ANA) synthesis. Since many different viruses are suspected to take part in the pathogenesis of different systemic autoimmune rheumatic diseases (SARDs), we examined whether coronavirus disease 2019 convalescents who suffer from mild to moderate disease have a higher risk of developing ANA and anti-β2-glicoprotein I IgG antibodies (β2 GPI). In a retrospective study, we examined 294 adults among volunteer blood donors divided into convalescents (N = 215) and healthy controls (N = 79). For ANA detection, we used line-blotting, a type of indirect immunofluorescence assay (IF), to determine antigenic specificity and ELISA for β2 GPI. We found a lower incidence of ANA in convalescents than in healthy controls, with the majority of these antibodies directed to antigens with no known clinical significance. Additionally, no participants were positive for β2 GPI in either group. Our results show that COVID-19 with mild to moderate symptoms in the generally healthy population does not induce the development of ANA or anti-β2 GPI antibodies for at least 6 months following the disease.

Deep sequencing reveals a DAP1 regulatory haplotype that potentiates autoimmunity in systemic lupus erythematosus

BackgroundSystemic lupus erythematosus (SLE) is a clinically heterogeneous autoimmune disease characterized by the development of anti-nuclear antibodies. Susceptibility to SLE is multifactorial, with a combination of genetic and environmental risk factors contributing to disease development. Like other polygenic diseases, a significant proportion of estimated SLE heritability is not accounted for by common disease alleles analyzed by SNP array-based GWASs. Death-associated protein 1 (DAP1) was implicated as a candidate gene in a previous familial linkage study of SLE and rheumatoid arthritis, but the association has not been explored further.ResultsWe perform deep sequencing across the DAP1 genomic segment in 2032 SLE patients, and healthy controls, and discover a low-frequency functional haplotype strongly associated with SLE risk in multiple ethnicities. We find multiple cis-eQTLs embedded in a risk haplotype that progressively downregulates DAP1 transcription in immune cells. Decreased DAP1 transcription results in reduced DAP1 protein in peripheral blood mononuclear cells, monocytes, and lymphoblastoid cell lines, leading to enhanced autophagic flux in immune cells expressing the DAP1 risk haplotype. Patients with DAP1 risk allele exhibit significantly higher autoantibody titers and altered expression of the immune system, autophagy, and apoptosis pathway transcripts, indicating that the DAP1 risk allele mediates enhanced autophagy, leading to the survival of autoreactive lymphocytes and increased autoantibody.ConclusionsWe demonstrate how targeted sequencing captures low-frequency functional risk alleles that are missed by SNP array-based studies. SLE patients with the DAP1 genotype have distinct autoantibody and transcription profiles, supporting the dissection of SLE heterogeneity by genetic analysis.

P137 Growing up on biologics: a case report of development of NMDAr encephalitis in a young person with JIA on abatacept

Abstract Background A 12-year-old female with JIA on biologic medication (IV abatacept every three weeks) presented with a first generalised tonic-clonic seizure on background of preceding headache and fatigue. The seizure self-terminated but disorientation and encephalopathy ensued. MRI brain demonstrated lesions with high signal intensity in the left periventricular and right occipital regions. The clinical picture and radiological imaging suggested a broad differential diagnosis including CNS infection, JC virus associated progressive multifocal leucoencephalomalacia (PML), acute disseminated encephalomyelitis (ADEM) and Anti-N-methyl-d-aspartate receptor (NMDAr) encephalitis. She was commenced on IV ceftriaxone, acyclovir and clarithromycin. All bloods including inflammatory markers and infection serology were unremarkable. CSF was acellular and JC virus PCR negative. NMDAr encephalitis was initially considered unlikely (pre-existing immunosuppression, abnormal MRI brain and no evidence of ovarian teratoma on abdominal MRI pelvis). However more classical clinical features developed including further seizures, significant movement disorder, cognitive dysfunction, sleep and speech dysfunction. Anti-NMDAr antibodies in both serum and CSF were positive. She made a good recovery following IV steroids, plasmapheresis and rituximab and was discharged home after a 10-week admission. NMDAr encephalitis developed three years after commencing abatacept treatment. Previous immune modulating treatment included methotrexate (since age 2 years), Etanercept (age 5-8 years) and Tocilizumab (aged 8-10 years). Flares of disease following a period of control necessitated the changes in therapy. Methods A literature review was conducted to explore the relationship between NMDAr encephalitis and biologic medication. A yellow card report and information request to abatacept manufacturer were also submitted. Results No previous cases of NMDAr encephalitis in patients on abatacept or paediatric cases related to biologic therapy are described. There are reports of adults developing NMDAr encephalitis on Adalumimab for Crohn’s disease and etanercept for rheumatoid arthritis. NMDAr encephalitis has also been described in patients on immune checkpoint inhibitors for malignant melanoma (nivolumab and ipilimumab). Known triggers of production of anti-NMDA receptor antibodies include tumours (ovarian teratoma; rarely associated in patients under 12 years) and viral infections. Developing autoimmune disorders on biologic medication is well reported, most notably psoriasis and inflammatory bowel disease. In relation to abatacept specifically, the development of anti-nuclear antibodies (ANA) and psoriasis have been described. However, patients with autoimmune disorders are known to be of increased risk for additional immune disease. A new cohort of patients are emerging who have received multiple biologic medications and the development of autoimmune conditions despite immunosuppression needs to be considered. Conclusion We describe the first case of NMDAr encephalitis occurring in a child on abatacept therapy, and the first case in JIA. We are unable to determine what contribution a history of autoimmune disease or immunomodulating therapy has made on its development in this case. Disclosures R. Close: None. P. Bale: None. K. Gallagher: None. G. Ambegaonkar: None. T. Rossor: None. N. Abbassi: None. K. Armon: None.

Anti-nuclear antibody development is associated with poor treatment response to biological disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis

BackgroundIt has been well known that TNF-α inhibitor (TNFi) treatment for patients with rheumatoid arthritis (RA) is associated with anti-nuclear antibody (ANA) development. We previously reported that ANA development was associated with poor outcomes of infliximab (IFX) treatment (1). However, no replication studies have been reported to date. In addition, whether the findings are true to general biological disease-modifying anti-rheumatic drugs (bDMARDs) is uncertain. MethodsTo evaluate an association between treatment response and ANA development during bDMARDs treatment in RA and to analyze correlates of ANA development, Japanese RA patients treated with (n = 657) or without (n = 211) bDMARDs as a first line bDMARD were enrolled from a single center cohort. ANA was measured by an indirect immunofluorescence assay at multiple time points of treatment. We analyzed associations between ANA development and insufficient response to treatment. Correlates of ANA development were also analyzed. ResultsANA development (≥2 times baseline levels) at 3 months and at 6–12 months after bDMARDs initiation were significantly associated with insufficient response at 3–12 months (odds ratio (OR)=3.51, p = 0.020) and at 12–24 months (OR = 3.16, p = 0.038), respectively. The associations remained significant after conditioning on the use of each bDMARD. The use of IFX (OR = 6.24, p < 0.001) was a risk for ANA development, and other TNFi showed the same tends as infliximab. On the other hand, non-TNFi bDMARDs were not associated with ANA development. ConclusionsANA development could be a marker of poor treatment response in RA patients undergoing bDMARDs treatment. Undefined factors might influence ANA development and subsequent poor bDMARDs outcome in RA.

Prescription medication use and antinuclear antibodies in the United States, 1999–2004

BackgroundClinical reports link specific medications with the development of antinuclear antibodies (ANA), but population-based evidence is limited. ObjectiveThe present study investigated associations between prescription medication use and ANA in a representative sample of the adult noninstitutionalized US population, first focusing on medications previously related to ANA and then considering all medications reported in the National Health and Nutrition Examination Survey (NHANES). MethodsBased on NHANES data (1999–2004) for 3608 adults (ages ≥18 years), we estimated odds ratios (ORs) and 95% confidence intervals (CIs) to assess associations between recent medication use and ANA (overall and in sex and age subgroups), adjusted for potential confounders and the survey sampling design. ResultsWe found no evidence that most medications previously associated with ANA in specific individuals were risk factors for ANA in the general population, although statistical power was limited for some medications. Overall, ANA were less prevalent in adults who recently used any prescription medications compared with those who did not (OR = 0.73; CI = 0.57,0.93), and likewise several classes of medications were inversely associated with ANA, including hormones (OR = 0.73; CI = 0.55,0.98), thiazide diuretics (OR = 0.43; CI = 0.24,0.79), sulfonylureas (OR = 0.41; CI = 0.19,0.89), and selective serotonin reuptake inhibitor antidepressants (OR = 0.65; CI = 0.42,0.98). Positive associations with ANA were seen for loop diuretics (OR = 1.72; CI = 1.03,2.88) in all adults, and for benzodiazepines (OR = 2.11; CI = 1.09,4.10) and bronchodilators (OR = 1.83; CI = 1.00,3.38) in older (ages ≥60) adults. Estrogens were positively associated with ANA in older women (OR = 1.80; CI = 1.00,3.23) but inversely associated with ANA in younger (ages 18–59) women (OR = 0.43; CI = 0.20,0.93). Regarding individual medications, ANA were positively associated with ciprofloxacin (OR = 4.23; CI = 1.21,14.8), furosemide (OR = 1.79; CI = 1.09,2.93), and omeprazole (OR = 2.05; CI = 1.03,4.10) in all adults, and with salmeterol (OR = 3.76; CI = 1.66,8.52), tolterodine (OR = 6.64; CI = 1.45,30.5), and triamterene (OR = 3.10; CI = 1.08,8.88) in older adults. Also, in younger adults, hydrochlorothiazide was inversely associated with ANA (OR = 0.44; CI = 0.20,0.98). ConclusionsOur findings in the general population do not confirm most clinically reported positive associations between specific medications and ANA in some individuals. However, novel positive ANA associations with other medications, as well as unexplained inverse associations with certain classes of medications and overall medication use, deserve further research to clarify the possible roles of medications as risk and protective factors in the development of autoantibodies and autoimmune disease.

Article Tools Print this article Indexing metadata How to cite item Email this article Email the author About The Authors Wisnu Barlianto Department of Pediatrics, Faculty of Medicine Brawijaya University/Dr. Saiful Anwar General Hospital, Malang, Indonesia Indonesia Hani Susianti Department of Clinical Pathology, Faculty of Medicine Brawijaya University/Dr. Saiful Anwar General Hospital, Malang, East Java, Indonesia Indonesia Singgih Wahono Department

Systemic Lupus Erythematosus (LES) is an autoimmune inflammatory disease characterized by the formation of anti-nuclear antibodies (ANA) and anti-double stranded DNA (anti-dsDNA) antibodies as diagnostic markers. Detection of such autoantibodies requires advanced equipment and trained personnel . This study was conducted to acquire candidate antigens that can be used for rapid test kit for practical and accurate detection of ANA and anti-dsDNA to speed up SLE diagnosis. Nuclear proteins and DNA derived from cell lines, hair follicles, and leukocytes of SLE patients and healthy individuals were isolated using QiaGEN kit and modified-manual procedure. Antigen-antibody bonds were tested by dot blot assay. The strongest binding between DNA antigens of a healthy individual and antibodies occurred at dilution factors of 1:5,120 for the antigen and 1:2,560 for the antibody. The strongest binding between nuclear protein antigens from the cell line and antibodies occurred at dilution factors of 1:512 for the antigen and 1:1,600 for the antibody. Nuclear antigens derived from cell line and DNA antigens of healthy individuals were antigen candidates for the development of ANA and anti-dsDNA rapid detection tests.

Aging-dependent decline of IL-10 producing B cells coincides with production of antinuclear antibodies but not rheumatoid factors

Aging is associated with development of autoimmunity. Loss of B cell tolerance in the elderly is suggested by an increased prevalence of anti-nuclear antibodies (ANAs) and rheumatoid factors (RFs). Accumulating evidence indicates that B cells also impact autoimmunity via secretion of cytokines. So far, few studies have directly assessed the effect of aging on the latter B cell function. Here, we determined if and how human aging influences the production of cytokines by B cells. In a cross-sectional study, we found that absolute numbers of circulating B cells were similar in 31 young (ages 19–39) and 73 old (age≥60) individuals. Numbers of transitional B cells (CD19+CD27−CD38HighCD24High) were decreased in old individuals, whereas numbers of naive and memory B cell subsets were comparable in young and old individuals. Short-term in vitro stimulation of whole blood samples revealed that numbers of B cells capable of producing TNF-α were similar in young and old individuals. In contrast, B cells capable of IL-10 production were decreased in old subjects. This decline of IL-10+ B cells was observed in old individuals that were ANA positive, and in those that were negative for both ANAs and RFs. However, IL-10+ B cells were remarkably well retained in the circulation of old subjects that were RF positive. Thus, pro-inflammatory TNF-α+ B cells are retained in the elderly, whereas IL-10+ B cells generally decline. In addition, our findings indicate that IL-10+ B cells may differentially impact the development of ANAs and RFs in the elderly.

Drug-like analogues of the parasitic worm-derived immunomodulator ES-62 are therapeutic in the MRL/Lpr model of systemic lupus erythematosus.

IntroductionES-62, a phosphorylcholine (PC)-containing immunomodulator secreted by the parasitic worm Acanthocheilonema viteae, protects against nephritis in the MRL/Lpr mouse model of systemic lupus erythematosus (SLE). However, ES-62 is not suitable for development as a therapy and thus we have designed drug-like small molecule analogues (SMAs) based around its active PC-moiety. To provide proof of concept that ES-62-based SMAs exhibit therapeutic potential in SLE, we have investigated the capacity of two SMAs to protect against nephritis when administered to MRL/Lpr mice after onset of kidney damage.MethodsSMAs 11a and 12b were evaluated for their ability to suppress antinuclear antibody (ANA) generation and consequent kidney pathology in MRL/Lpr mice when administered after the onset of proteinuria.ResultsSMAs 11a and 12b suppressed development of ANA and proteinuria. Protection reflected downregulation of MyD88 expression by kidney cells and this was associated with reduced production of IL-6, a cytokine that exhibits promise as a therapeutic target for this condition.ConclusionsSMAs 11a and 12b provide proof of principle that synthetic compounds based on the safe immunomodulatory mechanisms of parasitic worms can exhibit therapeutic potential as a novel class of drugs for SLE, a disease for which current therapies remain inadequate.

Frequency of antinuclear antibody positivity in patients with pattern hair loss.

Frequency of antinuclear antibody positivity in patients with pattern hair loss.

SAT0107 Antinuclear Antibody Positivity in RA Patients and Its Impact on Persistency of TNF Inhibitors

BackgroundRecently, it was reported that the antinuclear antibody (ANA) before starting anti-TNF treatment or development of ANA might be related with clinical response of TNF inhibitors or side effect of...

A case report of a lichenoid eruption in a young lady with Crohn’s disease

Background Crohn’s disease is the most frequent inflammatory bowel disease. The use of the TNFa inhibitors has completely revolutionized the therapeutical management of recalcitrant cases of Crohn’s disease [1]. Unfortunately many side effects have been described in association with the use of the TNFa inhibitors[2]. The development of antinuclear antibodies is frequently described but is not always associated with a pathological condition [3]. The occurrence of lupus like syndrome after initiating the TNFa inhibitors therapy is rare and estimated with a prevalence of 0,5% to 1% [4]. We described a case of a lupus-like syndrome induced by the infliximab in a patient treated for Crohn’s disease. Case report We report a case of a young woman suffering from Crohn’s disease since 2001. She was treated by infliximab at the dose of 5 mg/kg every 8 weeks since 2009. She developed in 2011 an extensive lichenoid eruption in her arms and legs [Figure 1]. She developed at the same time an important anemia. Her blood analyses showed the presence of antinuclear antibodies at a title of 1/640 and anti double strand DNA at a title of 25 UI that were negative before the initiation of the infliximab. Skin biopsies were performed and showed an histological picture of lupus. Six weeks after the withdrawal of the infliximab therapy the skin lesions were completely healed

Anticorps anti-médicament, auto-anticorps et traitements biologiques du psoriasis

The approval of substantial numbers of targeted biologic therapies (e.g., monoclonal antibodies, fusion proteins) for treatment of inflammatory diseases has positioned these drugs as important to fight chronic disorders such as psoriasis, rheumatoid arthritis and Crohn's disease. One of the concerns raised with the administration of biologic therapies is that because most of them are immunogenic glycoproteins they induce undesirable immune response leading to the generation of specific anti-drug antibodies (ADA). The development of "self" derived protein therapeutics (comprised of human germline sequence), such as recombinant "human" antibodies, helped to reduce the production of ADA but did not avoid all immunogenicity. Reduced efficacy and safety issues such as anaphylaxis or vasculitis accompany the development of ADA. In addition to immune reactions directed against the biologic therapies as a whole, some of them such as anti-TNFα are able to induce auto-immune response, notably antinuclear antibody (ANA). ANA development was associated with induced lupus and in psoriasis it was suggested that it may act as a marker of treatment failure to anti-TNFα. With a focus on psoriasis, this paper makes a current point on the consequences and challenges of the development of anti-drug antibodies and auto-immunity in patients who receive biologic therapies.

Formation of antinuclear and double-strand DNA antibodies and frequency of lupus-like syndrome in anti-TNF-α antibody-treated patients with inflammatory bowel disease

Anti-tumor necrosis factor (TNF) therapy used in patients with inflammatory bowel disease (IBD) has been associated with induction of autoantibodies including antinuclear antibodies (ANA), double-strand (ds) DNA antibodies, and the occurrence of lupus-like syndrome (LLS). However, the clinical relevance of autoantibody formation and predictive factors are unclear. 180 IBD patients treated with anti-TNF antibodies (infliximab or adalimumab, or infliximab and adalimumab consecutively) were analyzed regarding ANA and dsDNA antibody values and the development of LLS, including factors predicting the development of LLS. In all, 44.4% of anti-TNF-treated patients had ANA titers ≥1:240, while 15.6% had dsDNA serum levels ≥9 U/mL. However, only a minority of these patients experienced clinical symptoms of LLS; 8.9% presented with mild lupus-like symptoms with no need for intervention; 1.1% had severe symptoms consistent with LLS requiring immediate stop of anti-TNF therapy. Multivariate logistic regression analyses identified age as an independent risk factor for developing ANA ≥1:240 (P < 0.001) and LLS (P = 0.002), while concomitant immunosuppressive therapy was protective against autoantibody formation (ANA: P = 0.05) and LLS development (P = 0.04). There was a significant association between dsDNA antibody values ≥9 U/mL and LLS (P = 0.02) but not between ANA titers and LLS. dsDNA antibody levels ≥9 U/mL, but not ANA titers ≥1:240, are associated with clinical symptoms of LLS. IBD patients of higher age treated with anti-TNF-α antibodies are at increased risk for development of ANA and LLS, while concomitant immunosuppressive therapy may have a protective effect.

Somatic hypermutation as a generator of antinuclear antibodies in a murine model of systemic autoimmunity

Systemic lupus erythematosus (SLE) is characterized by high-avidity IgG antinuclear antibodies (ANAs) that are almost certainly products of T cell–dependent immune responses. Whether critical amino acids in the third complementarity-determining region (CDR3) of the ANA originate from V(D)J recombination or somatic hypermutation (SHM) is not known. We studied a mouse model of SLE in which all somatic mutations within ANA V regions, including those in CDR3, could be unequivocally identified. Mutation reversion analyses revealed that ANA arose predominantly from nonautoreactive B cells that diversified immunoglobulin genes via SHM. The resolution afforded by this model allowed us to demonstrate that one ANA clone was generated by SHM after a VH gene replacement event. Mutations producing arginine substitutions were frequent and arose largely (66%) from base changes in just two codons: AGC and AGT. These codons are abundant in the repertoires of mouse and human V genes. Our findings reveal the predominant role of SHM in the development of ANA and underscore the importance of self-tolerance checkpoints at the postmutational stage of B cell differentiation.

Increased disease activity is associated with altered sleep architecture in an experimental model of systemic lupus erythematosus

SLEEP IS VITAL TO HEALTH AND QUALITY OF LIFE, WHEREAS POOR SLEEP IS ASSOCIATED WITH ADVERSE HEALTH CONSEQUENCES. THIS IS AN IMPORTANT issue in its own right because sleep deprivation is becoming a more frequent and more accepted occurrence in modern society. In addition, sleep disorders have been observed in a number of chronic inflammatory conditions such as autoimmune diseases. Some of the clinical states associated with sleep disturbances include rheumatoid arthritis, fibromyalgia, and systemic lupus erythematosus (SLE).1 Nevertheless, it is unclear whether the sleep disruption that is observed in patients with these diseases is a result of factors associated with the disease—such as pain, depression, and stress2—or the result of dysregulation of the relationship between sleep and the immune system. Sleep disturbances are often reported by patients with SLE, and this may be associated with fatigue,3 a symptom that affects up to 80% of patients with SLE.4 According to Valencia-Flores and colleagues,5 these patients are sleepier during the day by virtue of sleep fragmentation due to more arousals and sleep-stage transitions (SST). In addition, the disease is exacerbated by sleep disruption, resulting in decreased sleep efficiency and less delta sleep. Additional polysomnographic findings associated with disease activity include an increased percentage of stage 1 sleep and alpha intrusions into non-rapid eye movement sleep. Furthermore, sleep apnea, periodic leg movements during sleep and narcolepsy have been associated with SLE.6 Much of our current knowledge of the pathogenesis of SLE is based on inference from a murine model, the New Zealand Black/New Zealand White (NZB/NZW)F1 hybrid strain. These mice spontaneously develop an autoimmune disease that closely resembles the immunologic and clinical characteristics of human SLE, such as high titer levels of antinuclear antibodies (ANA) associated with the development of rapidly progressive and lethal glomerulonephritis. Similar to its characteristics in humans, the disease is most common in female mice. However, there is no evidence about sleep patterns in this experimental model of SLE. Recent data from our laboratory indicate the importance of adequate sleep in (NZB/NZW)F1 mice. We observed that mice submitted to sleep deprivation exhibited an earlier onset of the disease, as reflected by the increased ANA titer levels.7 The purpose of the present study was, therefore, to evaluate the sleep patterns in a spontaneous experimental model of SLE, which offers a great opportunity to study the interaction between sleep and autoimmune disease. The disease course in (NZB/NZW)F1 mice was also assessed by following the development of ANA and pain sensitivity. A characterization of the sleep architecture that is associated with the onset, progress, and severe phases of this disease is presented in this article.

Antinuclear antibodies associate with loss of response to antitumour necrosis factor-α therapy in psoriasis: a retrospective, observational study

An increasing number of patients with severe psoriasis are failing to respond to antitumour necrosis factor (TNF)-alpha therapy (etanercept, infliximab and adalimumab).We observed that many of these patients developed antinuclear antibodies (ANA) and antidouble-stranded DNA (anti-dsDNA) antibodies while on treatment prompting us to investigate whether their development is associated with anti-TNF treatment failure.All patients with psoriasis who had received anti-TNF therapies were identified and their blood results and treatment histories were obtained from electronic patient records and case notes.A total of 97 patients had been treated with anti-TNF agents (60 were on their first agent, 22 had been on and stopped one agent, nine had been on and stopped two agents and six had been on and stopped all three agents). ANA developed in 17% of patients on their first treatment, 54% of patients who had failed one treatment, 78% of patients who had failed two treatments and 83% of patients who had failed all three treatments. Anti-dsDNA antibodies developed in 2%, 27%, 33% and 83% of patients from the same respective groups. Significantly, the antibodies developed before treatment had failed with all three agents and their development was not related to the total time that patients had been on anti-TNF therapy.This study suggests that the development of ANA and anti-dsDNA antibodies on anti-TNF treatment may act as a marker of forthcoming treatment failure. Large-scale prospective studies are required to assess the importance of this observation.

Drug‐induced Lupus Associated With Infliximab and Adalimumab in an Adolescent With Crohn Disease

Drug‐induced Lupus Associated With Infliximab and Adalimumab in an Adolescent With Crohn Disease

Traitement du lupus érythémateux chronique par sulfasalazine (18 cas)

To evaluate the efficacy and the tolerance of sulfasalazine in the treatment of chronic lupus erythematosus (CLE).We prescribed sulfasalazine (2 g/d) for 18 patients with severe CLE, all of whom had contraindications for or treatment failure with antimalarial drugs and thalidomide. This study analyses their response to treatment, duration of therapy, reasons for stopping, adverse effects, and the influence of the N-acetyltransferase 2 (NAT2) phenotype.We observed 10 complete and 3 partial responses, and 4 patients maintained complete response for at least 7 years. Eight patients experienced adverse effects, and 2 needed to stop treatment (because of photosensitization and development of antinuclear antibodies). All side effects occurred in the first 3 months of treatment. None of the 18 patients developed systemic lupus erythematosus. Of the 10 complete responders, 9 were rapid acetylators (RA), while 4 of the 5 who failed to respond were slow acetylators (SA). Leukopenia and photosensitization were observed in SA patients, while different side effects occurred in RA patients (headaches, diarrhea, moderate increase in liver enzymes and antinuclear antibodies).These findings confirm our earlier reports and demonstrate that sulfasalazine can be used successfully to treat severe CLE. NAT2 genotyping before initiating treatment helps to identify potential responders and avoid side effects. In RA patients, sulfasalazine can be an alternative to thalidomide after antimalarial drugs, whereas in SA patients, it should remain a third-line treatment, to be used only after antimalarials and thalidomide.