Discrepant Perception of Lupus Disease Activity

Background:Systemic lupus erythematous (SLE) is a systemic autoimmune disease with diverse etiological factors. It was recognized that interferon (IFN) signature involved in the progress of SLE. NLRP12 (NOD-like receptor family (NLR) pyrin domain containing 12) is a pyrin containing NLR protein that we had linked its new biological function to the cross-regulation of Toll like receptor (TLRs) and Rig-I like receptor (RIG-I) pathways. NLPR12 acts as an innate immune check-point in regulating type I IFNs expression during TLRs and RIG-I activation. The importance of NLRP12 in lupus disease activity remained to be elucidated.Objectives:To clarify the role of NLRP12 in regulating the interferon signature.Methods:Peripheral blood mononuclear cells (PBMCs) were collected from SLE patients and healthy donors for analysis of NLRP12 and IFN-α gene expression by RT-QPCR. PBMCs were applied for Chromatin immuneprecipitation (ChIP) assay and electrical mobility shift assay (EMSA) to determine the putative transcription factor that regulates NLRP12 expression. An involvement of epigenetic regulation of NLRP12 expression in SLE patients was also analyzed. Bone marrow derived dendritic cells (BMDCs) were collected from wild type mouse and Nlrp12 knocked-out mice. Another CD14+ monocytes were isolated from 10 cases of lupus patients and 8 cases of healthy control, following by stimulating different type of nucleic acids, and IFN-α and IL-6 were measured with ELISA assay. CD14+ monocytes in lupus patients were also pre-treated with IFNAR2 antibody for further nucleic acid stimulation. Two mice models were applied for evaluation the role of Nlrp12: intraperitoneal injection of TMPD (2,6,10,14-tetramethylpentadecane, or pristane) in C57BL/6 mice and Faslpr mice. Both models were conducted with and without Nlrp12 knockout.Results:NLRP12 expression was significantly lower in PBMC isolated from SLE patients compared to healthy donors. The inverse correlation was observed in NLRP12 and IFNA gene expression as well as NLRP12 expression and amount of double-stranded DNA autoantibody in SLE patients. NLRP12 expression showed negative correlations with IFN-α treatment, as well as herpes simplex virus-1 (HSV-1) infection. Results from ChIP and EMSA analysis indicated a potential transcription factor 1 (TF-1) regulating NLRP12 promoter activity. TF-1 lead to transcriptional suppression of NLRP12 in SLE PBMC, and it was gradually induced after IFN treatment. Recruitment of TF-1 to NLRP12 promoter in SLE PBMC compared to the healthy PBMC was detected, and increased when treating with IFN. Human CD14+ monocytes collected from lupus and healthy control stimulating with different type of nucleic acids revealing significant increasing level of IFN-α and IL-6 in lupus patients. Among animal models, both pristine induced mice and Faslpr mice revealed increasing autoantibodies production and severity of glomerulonephritis in Nlrp12-/- group in comparison with Nlrp12+/+ ones, indicating the role of NLRP12 in maintaining positive interferon signature as well as disease activity.Conclusion:Expression level of NLRP1.2 has been demonstrated to be a biomarker of disease activity in SLE patients. The NLRP12 was involved in the interferon signature, which was also negatively regulated by TF-1. Both clinical samples and animal models revealed NLRP12 in maintaining the positive interferon signature, indicating the possible role of exacerbating factor for lupus disease activity.Disclosure of Interests:None declared

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Optimal Frequency of Visits for Patients with Systemic Lupus Erythematosus to Measure Disease Activity Over Time

The Journal of Rheumatology ◽

10.3899/jrheum.100575 ◽

2010 ◽

Vol 38 (1) ◽

pp. 60-63 ◽

Cited By ~ 11

Author(s):

DOMINIQUE IBAÑEZ ◽

DAFNA D. GLADMAN ◽

ZAHI TOUMA ◽

MANDANA NIKPOUR ◽

MURRAY B. UROWITZ

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Activity Index ◽

Disease Activity Index ◽

Systemic Lupus ◽

The Mean ◽

Over Time ◽

Measure Disease Activity ◽

Lupus Disease Activity

Objective.Adjusted mean Systemic Lupus Erythematosus Disease Activity Index (SLEDAI; AMS) measures lupus disease activity over time. Our aim was to determine optimal visit frequency for calculating AMS.Methods.Patients followed monthly for 12 consecutive visits were included. AMS was calculated using all of the SLEDAI 2000 (AMSGOLD using all 12 visits), only quarterly visits (AMS3, using visits 3 months apart), semiannual visits (AMS6, using first, middle, and last visits only), and annual visits (AMS12, using only the first and last visits). Comparisons of AMS3, AMS6, and AMS12 with AMSGOLD are made using descriptive statistics.Results.Seventy-eight patients were included (92% women, mean age at SLE diagnosis 30.1 yrs and at study start 46.2 yrs). The mean (SD) AMSGOLD for the entire year was 2.05 (1.66), for AMS3 1.99 (1.65), for AMS6 2.12 (1.87), and for AMS12 2.08 (1.83). Mean (SD) of the absolute differences with AMSGOLD: for AMS3 0.29 (0.33), for AMS6 0.45 (0.59), and for AMS12 0.61 (0.58). Differences that were < 0.5 were considered minimal while those ≥ 1 were deemed important. Comparing AMSGOLD to AMS3, 82% of the differences were minimal and 3% were important. When comparing to AMS6, 68% were minimal and 10% were important, while comparing to AMS12, 50% were minimal and 21% were important.Conclusion.Usual clinic visits occurring quarterly offer a good estimation of disease activity over a 1-year period and are preferred over semiannual and annual visits.

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Inverse Association Between Antiviral Immunity and Lupus Disease Activity

Viral Immunology ◽

10.1089/vim.2018.0087 ◽

2018 ◽

Vol 31 (10) ◽

pp. 689-694

Author(s):

Yu-Jih Su ◽

Wen-Chan Chiu ◽

Ho-Chang Kuo

Keyword(s):

Disease Activity ◽

Antiviral Immunity ◽

Inverse Association ◽

Lupus Disease Activity

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FRI0353 A Longitudinal Analysis of Change in Lupus Disease Activity Pattern in Hopkins Lupus Cohort Using A Multistate Markov Model Approach: Table 1.

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2016-eular.4493 ◽

2016 ◽

Vol 75 (Suppl 2) ◽

pp. 562.3-562

Author(s):

W. Fu ◽

M. Petri

Keyword(s):

Markov Model ◽

Disease Activity ◽

Longitudinal Analysis ◽

Activity Pattern ◽

Analysis Of Change ◽

Lupus Disease Activity ◽

Model Approach

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Understanding patient-provider discordance in adolescents with lupus: The role of pain and antidepressant medication use

Health Psychology Open ◽

10.1177/2055102920977714 ◽

2020 ◽

Vol 7 (2) ◽

pp. 205510292097771

Author(s):

Kathleen Kenney-Riley ◽

Shari Salzhauer Berkowitz ◽

Kimberly Rapoza

Keyword(s):

Disease Activity ◽

Secondary Analysis ◽

Medication Use ◽

Antidepressant Medication ◽

Childhood Arthritis ◽

Pain Scores ◽

Pediatric Lupus ◽

Research Alliance ◽

Lupus Disease Activity

The current study examines depression and pain as potential contributors to patient-provider discordance in the assessment of lupus disease activity. The study conducted a secondary analysis of data obtained from the Childhood Arthritis and Rheumatology Research Alliance registry, with N = 859 adolescent participants. Assessments of pain, disease activity, and antidepressant medication use were collected from the patient and provider. Results indicated that depression might be underdiagnosed in pediatric lupus patients. While psychotropic medication and pain scores were independently related to greater patient-provider discordance regarding health status, pain mediated this relationship. Implications for treatment outcomes are discussed.

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