Isoniazid disposition, comparison of isoniazid phenotyping methods in and acetylator distribution of Japanese patients with idiopathic systemic lupus erythematosus and control subjects.

Objective.MicroRNA (miRNA) are short noncoding RNA that regulate genes and are both biomarkers and mediators of disease. We used small RNA (sRNA) sequencing and machine learning methodology to develop an miRNA panel to reliably differentiate between rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) and control subjects.Methods.Plasma samples from 167 RA and 91 control subjects who frequency-matched for age, race, and sex were used for sRNA sequencing. TIGER was used to analyze miRNA. DESeq2 and random forest analyses were used to identify a prioritized list of miRNA differentially expressed in patients with RA. Prioritized miRNA were validated by quantitative PCR, and lasso and logistic regression were used to select the final panel of 6 miRNA that best differentiated RA from controls. The panel was validated in a separate cohort of 12 SLE, 32 RA, and 32 control subjects. Panel efficacy was assessed by area under the receiver operative characteristic curve (AUC) analyses.Results.The final panel included miR-22-3p, miR-24-3p, miR-96-5p, miR-134-5p, miR-140-3p, and miR-627-5p. The panel differentiated RA from control subjects in discovery (AUC = 0.81) and validation cohorts (AUC = 0.71), seronegative RA (AUC = 0.84), RA remission (AUC = 0.85), and patients with SLE (AUC = 0.80) versus controls. Pathway analysis showed upstream regulators and targets of panel miRNA are associated with pathways implicated in RA pathogenesis.Conclusion.An miRNA panel identified by a bioinformatic approach differentiated between RA or SLE patients and control subjects. The panel may represent an autoimmunity signature, perhaps related to inflammatory arthritis, which is not dependent on active disease or seropositivity.

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Prognostic Impact of Genetic Variants of MECP2 and TIRAP on Clinical Outcomes of Systemic Lupus Erythematosus with and without Nephritis

Biomolecules ◽

10.3390/biom11091378 ◽

2021 ◽

Vol 11 (9) ◽

pp. 1378

Author(s):

Safaa I. Tayel ◽

Nashwa M. Muharram ◽

Dina S. Fotoh ◽

Hany S. Elbarbary ◽

Huda I. Abd-Elhafiz ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Vitamin A ◽

Lupus Erythematosus ◽

Clinical Impact ◽

Prognostic Impact ◽

Laboratory Measurements ◽

Systemic Lupus ◽

Control Subjects ◽

And Control ◽

Personalize Medicine

Systemic lupus erythematosus (SLE) is a chronic autoimmune illness with a growing prevalence in many populations. Few studies have examined genetic predisposition to SLE, so we aimed to examine the clinical impact of the genetic polymorphisms MECP2 rs2734647and TIRAP rs8177374 on the outcomes and therapeutic precision of SLE with and without nephritis. This study included 110 SLE patients—divided into 63 with lupus nephritis (LN), and 47 without nephritis—and 100 controls. Laboratory measurements including CRP, ESR, ACR, CBC, anti-ds-DNA, vitamin A, C3, and C4 were carried out, along with genotyping of MECP2 rs2734647and TIRAP rs8177374 by real-time PCR and sequencing. Treg %, vitamin A, C3, and C4 were lower, whereas Th17 % was higher, in patients vs. controls (p < 0.001). The T allele of MECP2 rs2734647 was higher in LN than in non-nephritis and control subjects. Moreover, the T allele of TIRAP rs8177374 was higher in LN than in non-nephritis and control subjects. The MECP2 and TIRAP genes could play a role in predisposition to SLE, and can also predict disease progress to nephritis, helping to personalize medicine.

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Reliability of the SF-36 in Japanese patients with systemic lupus erythematosus and its associations with disease activity and damage: a two-consecutive year prospective study

Lupus ◽

10.1177/0961203317725586 ◽

2017 ◽

Vol 27 (3) ◽

pp. 407-416 ◽

Cited By ~ 8

Author(s):

S Baba ◽

Y Katsumata ◽

Y Okamoto ◽

Y Kawaguchi ◽

M Hanaoka ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Mental Component Summary ◽

Short Form ◽

Bodily Pain ◽

Damage Index ◽

Japanese Patients ◽

Systemic Lupus ◽

Sf 36

We aimed to validate the reliability of the Medical Outcomes Study Short Form-36 (SF-36) among Japanese patients with systemic lupus erythematosus (SLE). Japanese patients with SLE ( n = 233) completed the SF-36 and other related demographic questionnaires, and physicians simultaneously completed the SLE Disease Activity Index 2000 (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics Damage Index (SDI). Patients were prospectively followed for a repeat assessment the following year. The SF-36 subscales demonstrated acceptable internal consistency (Cronbach’s α of 0.85–0.89), and an overall good test–retest reliability (intraclass correlation coefficient >0.70). The average baseline SF-36 subscale/summary scores except for “bodily pain” were significantly lower than those of the Japanese general population ( p < 0.05). The SDI showed an inverse correlation with the SF-36 subscale/summary scores except for “vitality” and “mental component summary” at baseline, whereas the SLEDAI-2K did not. In the second year, “social functioning” and “mental component summary” of the SF-36 deteriorated among patients whose SDI or SLEDAI-2K score increased (effect sizes < −0.20). In conclusion, the SF-36 demonstrated acceptable reliability among Japanese patients with SLE. Health-related quality of life measured by the SF-36 was reduced in Japanese patients with SLE and associated with disease damage, rather than disease activity.

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Screening for Depression in Systemic Lupus Erythematosus with the British Columbia Major Depression Inventory

Psychological Reports ◽

10.1177/003329410209000306.2 ◽

2002 ◽

Vol 90 (3_part_2) ◽

pp. 1091-1096 ◽

Cited By ~ 1

Author(s):

Grant L. Iverson

Keyword(s):

Systemic Lupus Erythematosus ◽

British Columbia ◽

Major Depression ◽

Lupus Erythematosus ◽

Community Control ◽

Control Group ◽

Systemic Lupus ◽

Control Subjects ◽

Major Depression Inventory ◽

Falling Asleep

Accurate identification of depression in patients with systemic lupus erythematosus (SLE) is particularly complicated because the vegetative symptoms of depression also reflect core features of this autoimmune disease. Self-reported symptoms in patients with SLE ( n = 103) and community control subjects ( n = 136) were examined with the British Columbia Major Depression Inventory and the Beck Depression Inventory-II. The patients with lupus obtained higher scores on most items of the former inventory. A logistic regression analysis assessed whether a subset of these items were uniquely related to group membership. Clinically significant fatigue was much more common in patients with lupus than in the control group. Two items relating to sleep disturbance also entered the equation as unique predictors. The three-variable model resulted in 85% of the control subjects and 66% of the patients being correctly classified. A subset of patients with depression, according to the Beck inventory (17 or higher), were selected ( n = 41). Their most frequently endorsed symptoms on the British Columbia Inventory were fatigue (90.2%), trouble falling asleep (70.7%), cognitive difficulty (61%), and psychomotor slowing (58.5%). Only 29.3% reported significant sadness. 15% of these subjects were classified as not depressed, 46% as possibly depressed, and 39% as probably depressed on the British Columbia Inventory. It is advisable to assess whether patients are experiencing significant sadness or loss of interest before concluding that a high score on a screening test corresponds to probable depression.

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Anti-mannose binding lectin antibodies in sera of Japanese patients with systemic lupus erythematosus

Clinical & Experimental Immunology ◽

10.1111/j.1365-2249.2004.02477.x ◽

2004 ◽

Vol 136 (3) ◽

pp. 585-590 ◽

Cited By ~ 26

Author(s):

R. TAKAHASHI ◽

A. TSUTSUMI ◽

K. OHTANI ◽

D. GOTO ◽

I. MATSUMOTO ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Japanese Patients ◽

Mannose Binding Lectin ◽

Systemic Lupus ◽

Mannose Binding ◽

Binding Lectin

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Abstract 10: Disparate Temporal Regulation of Blood Pressure by Estrogens During Systemic Lupus Erythematosus.

Hypertension ◽

10.1161/hyp.60.suppl_1.a10 ◽

2012 ◽

Vol 60 (suppl_1) ◽

Author(s):

Emily L Gilbert ◽

Keisa W Mathis ◽

Marcia Venegas-Pont ◽

Michael J Ryan

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Progression ◽

Lupus Erythematosus ◽

Population Based ◽

Protective Role ◽

Young Female ◽

Sham Operation ◽

Systemic Lupus ◽

Temporal Regulation ◽

And Control

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that predominantly affects young women. Due to this partiality towards women, estrogen is commonly implicated in disease development. The potential for estrogens to promote SLE disease progression stems from data showing that removal of estrogens in young female mice with SLE (6-8 week old NZBWF1 mice) delays the development of renal injury and mortality. The primary cause of mortality in women with SLE is cardiovascular disease, and hypertension, a major cardiovascular risk factor, is highly prevalent in this patient population. Based on the presumed role of estrogen to promote SLE, we hypothesized that estrogen promotes hypertension during SLE. To test this, 30 week old SLE mice (NZBWF1) and control mice (NZW/LacJ) were subjected to either ovariectomy (OVX) or a sham operation and a subset of these mice were replete with 17β-estradiol (E2, 5μg/mouse, s.c., 2x/week). At 34 weeks of age, mean arterial pressure (MAP in mmHg) was measured by carotid catheter in conscious freely moving mice. MAP was higher in SLE sham mice compared to control shams (133±3, n=17 vs. 120±3, n=13, p<0.05). Contrary to our hypothesis, OVX at 30 weeks exacerbated the hypertension (154±3, n=9, p<0.05 vs. SLE sham) and prevalence of albuminuria in mice with SLE (83%, 10 of 12 vs 36%, 5 of 14 measured by dipstick > 100 mg/dL). OVX did not alter MAP (115±3, n=9) or albuminuria in control mice. The hypertensive response to OVX was prevented in OVX SLE mice replete with E2 (133±4, n=3) suggesting a protective role for E2 against SLE-associated hypertension. Because previous studies showed that estrogen removal in young mice delayed SLE disease progression, we tested whether OVX starting at 8 weeks of age delayed the development of hypertension. OVX in young SLE mice did not significantly alter the progression of SLE-associated hypertension (141±4, n=4 measured at 34 weeks of age). Consistent with previous work of others, OVX in young SLE mice reduced the prevalence of albuminuria (20%, 1 of 5 vs 33%, 1 of 3). These data suggest that estrogen has a complex temporal role in the pathogenesis of SLE with the potential to promote disease early in life, but protect against the progression of SLE associated hypertension later in the course of the disease.

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Expansion of regulatory T cells using low-dose interleukin-2 attenuates hypertension in an experimental model of systemic lupus erythematosus

AJP Renal Physiology ◽

10.1152/ajprenal.00616.2018 ◽

2019 ◽

Vol 317 (5) ◽

pp. F1274-F1284 ◽

Cited By ~ 2

Author(s):

Erin B. Taylor ◽

Jennifer M. Sasser ◽

Kenji J. Maeda ◽

Michael J. Ryan

Keyword(s):

Systemic Lupus Erythematosus ◽

Mean Arterial Pressure ◽

Arterial Pressure ◽

Lupus Erythematosus ◽

Renal Injury ◽

Low Dose ◽

Interleukin 2 ◽

Autoimmune Disorder ◽

Systemic Lupus ◽

And Control

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disorder that is characterized by prevalent hypertension, renal injury, and cardiovascular disease. Numerous studies have reported a low prevalence and/or impaired function of regulatory T (TREG) cells in both patients with SLE and murine models of the disease. Evidence suggests that TREG cell dysfunction in SLE results from a deficiency in IL-2. Recent studies have reported that low-dose IL-2 therapy expands TREG cells in mouse models of SLE, but whether expanding TREG cells protects against hypertension and renal injury during SLE is unclear. To examine this question, female SLE (NZBWF1) and control (NZW) mice were injected with vehicle or recombinant mouse IL-2 three times in 24 h followed by single maintenance doses every 5 days for 4 wk. Treatment with IL-2 effectively expanded TREG cell populations in the peripheral blood, spleen, and kidneys. Circulating levels of anti-dsDNA IgG autoantibodies, a marker of SLE disease activity, were higher in SLE mice compared with control mice but were unaffected by IL-2 treatment. As previously reported by our laboratory, mean arterial pressure, measured in conscious mice by a carotid catheter, was higher in SLE mice than in control mice. Mean arterial pressure was significantly lower in IL-2-treated SLE mice compared with vehicle-treated SLE mice, suggesting that expanding TREG cells using low-dose IL-2 attenuates the development of hypertension. While the mechanism for the protection against hypertension is unclear, it does not appear to be related to the delay of SLE disease progression.

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