Lupus Severity Index Research Articles

Molecular Taxonomy of Systemic Lupus Erythematosus Through Data-Driven Patient Stratification: Molecular Endotypes and Cluster-Tailored Drugs.

ObjectivesTreatment of Systemic Lupus Erythematosus (SLE) is characterized by a largely empirical approach and relative paucity of novel compound development. We sought to stratify SLE patients based on their molecular phenotype and identify putative therapeutic compounds for each molecular fingerprint.MethodsBy the use of whole blood RNA-seq data from 120 SLE patients, and in a data-driven, clinically unbiased manner, we established modules of commonly regulated genes (molecular endotypes) and re-stratified patients through hierarchical clustering. Disease activity and severity were assessed using SLEDAI-2K and Lupus Severity Index, respectively. Through an in silico drug prediction pipeline, we investigated drugs currently in use, tested in lupus clinical trials, and listed in the iLINCS prediction databases, for their ability to reverse the gene expression signatures in each molecular endotype. Drug repurposing analysis was also performed to identify perturbagens that counteract group-specific SLE signatures.ResultsMolecular taxonomy identified five lupus endotypes, each characterized by a unique gene module enrichment pattern. Neutrophilic signature group consisted primarily of patients with active lupus nephritis, while the B-cell expression group included patients with constitutional features. Patients with moderate severity and serologic activity exhibited a signature enriched for metabolic processes. Mild disease was distributed in two groups, exhibiting enhanced basic cellular functions, myelopoiesis, and autophagy. Bortezomib was predicted to reverse disturbances in the “neutrophilic” cluster, azathioprine and ixazomib in the “B-cell” cluster, and fostamatinib in the “metabolic” patient subgroup.ConclusionThe clinical spectrum of SLE encompasses distinct molecular endotypes, each defined by unique pathophysiologic aberrancies potentially reversible by distinct compounds.

High Disease Severity Among Asian Patients in a US Multiethnic Cohort of Individuals With Systemic Lupus Erythematosus.

Knowledge about systemic lupus erythematosus (SLE) outcomes among US Asian patients is lacking. The present study was undertaken to examine SLE disease activity, severity, and damage among Asian patients of primarily Chinese and Filipino descent in a multiethnic cohort. California Lupus Epidemiology Study (n = 328) data were analyzed. Data were collected in English, Cantonese, Mandarin, or Spanish using validated instruments for disease activity (Systemic Lupus Erythematosus Disease Activity Index), disease severity (Lupus Severity Index [LSI]), and disease damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index). We assessed differences in SLE outcomes among racial/ethnic groups using multivariable linear regression including interaction terms for age at diagnosis and race/ethnicity. Asian was the largest racial/ethnic group (38% [Chinese = 22%; Filipino = 9%; Other = 7%]). Average age at diagnosis was younger among Asian patients (27.9 years), particularly Filipino patients (22.2 years), compared with White (29.4 years) and Black patients (34.0 years). After adjustment, disease activity and damage were not significantly different across groups. Disease severity among Asian patients was significantly higher than among White patients (LSI score 7.1 versus 6.5; P < 0.05) but similar among Black and Hispanic patients. Early age at diagnosis was associated with greater organ damage among Asian, Black, and Hispanic patients, but not White patients. SLE was more severe among US Asian patients compared to White patients. Filipinos were affected at strikingly young ages. Asian patients and non-White groups with younger age at diagnosis had greater organ damage than White patients. Such racial/ethnic distinctions suggest the need for heightened clinical awareness to improve health outcomes among Asian patients with SLE. Further study of SLE outcomes across a range of US Asian subgroups is important.

Autoimmune Regulator Gene Polymorphisms in Egyptian Systemic Lupus Erythematosus Patients: Preliminary Results.

Background Systemic lupus erythematosus (SLE) is a systemic autoimmune disease. The autoimmune regulator (AIRE) is a master regulator of self-tolerance development. AIRE mutations lead to the development of autoimmune polyglandular syndrome type 1 while AIRE polymorphisms have been linked to organ-specific autoimmunity. The study is aimed at addressing the association between AIRE polymorphisms, rs2075876 (G > A) and rs760426 (A > G), and SLE susceptibility and expression in Egyptian patients. Methods Ninety-nine patients were included. One hundred and ten, and 123 control subjects were genotyped for rs2075876 and rs760426, respectively. Lupus severity was assessed using the Lupus Severity of Disease Index and Lupus Severity Index (LSI). Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) damage index was considered. Genotyping was done using StepOne Real-Time PCR. Results. AIRE rs760426 GG was more frequent in the patients under the genotype level (14.1% vs. 4.9%, p = 0.032) and recessive model (14.1% vs. 4.9%, p = 0.017, OR = 3.2 (1.2-8.7)). Musculoskeletal involvement and nephritis were associated with AIRE rs2075876 under the dominant (97.9% vs. 80.8%, p = 0.009, OR = 11 (1.3-89.2)) and recessive models (100% vs. 69.3%, p = 0.032), respectively; and both were linked to AIRE rs2075876 at the allelic level: 98.3% vs. 85%, p = 0.005, OR = 10.1 (1.3-76.6) and 82.8% vs. 68.6, p = 0.041, OR = 2.2 (1-4.7), respectively. Patients with AIRE rs2075876 A alleles had a higher damage index ( 1 ± 1.3 vs. 0.6 ± 1.1, p = 0.045) while the LSI was greater in patients with AIRE rs2075876 (8.5 ± 0.5 vs. 7.8 ± 1.3, p = 0.002) and rs760426 (8.6 ± 11 vs. 7.8 ± 1.2, p = 0.031) under the recessive models. Conclusion. AIRE rs760426 could share in SLE susceptibility while AIRE rs2075876 could influence the disease expression and burden in Egyptian patients.

Cell-bound complement activation products associate with lupus severity in SLE

ObjectivesTo evaluate the association between lupus severity and cell-bound complement activation products (CB-CAPs) or low complement proteins C3 and C4.MethodsAll subjects (n=495) fulfilled the American College of Rheumatology (ACR) classification...

Spectrum of cutaneous lupus erythematosus in South Africans with systemic lupus erythematosus.

Cutaneous involvement is very common in systemic lupus erythematosus. We describe the prevalence and spectrum of lupus-specific (cutaneous lupus erythematosus) and non-specific cutaneous features amongst mostly black South Africans with systemic lupus erythematosus. A retrospective record review of 298 South Africans (262 blacks and 36 non-blacks) with systemic lupus erythematosus was carried out. Cutaneous features were classified according to the Gilliam and Sontheimer classification of cutaneous lupus. Most (81.5%) patients were black African females. The mean (SD) age at diagnosis and follow-up duration were 35.0 (11.8) and 8.0 (5.9) years, respectively. Cutaneous lupus erythematosus was seen in 76.1% of patients, mainly chronic cutaneous lupus erythematosus with the discoid lupus erythematosus subtype seen in 52.1% of patients. Acute cutaneous lupus erythematosus was seen in 30.2% of patients and was more common in non-blacks than blacks (odds ratio = 3.8 (1.9-7.9)); localized acute cutaneous lupus erythematosus was more common than generalized acute cutaneous lupus erythematosus (odds ratio = 2.6 (1.6-4.4)). Non-specific cutaneous features occurred in 77.2%, with oral/nasal ulcers and Raynaud's phenomenon each occurring in approximately 40% of patients. Diffuse melanonychia at initial diagnosis was present in 37.4% of patients and was more common in blacks than non-blacks (odds ratio = 3.1 (1.3-7.3)). Acute cutaneous lupus erythematosus was associated with renal disease (odds ratio = 2.8 (1.6-4.7)) and chronic cutaneous lupus erythematosus with arthritis (odds ratio = 2.02 (1.24-3.29)). Diffuse melanonychia was associated with less renal disease and anti-dsDNA antibody positivity (odds ratio = 0.4 (0.3-0.7) and 0.4 (0.2-0.6), respectively) and significantly lower lupus severity index scores (mean (SD) = 5.99 (1.11) vs 6.56 (1.36) in patients with no melanonychia, p < 0.05)). In this study of South Africans with systemic lupus erythematosus, the skin was the most commonly affected organ. In general, cutaneous lupus erythematosus was associated with less severe systemic disease. Acute cutaneous lupus erythematosus was less common in blacks, whereas discoid lupus erythematosus was more common than reported in Caucasians. Diffuse melanonychia was a distinctive finding and was associated with milder systemic disease.

Burden of comorbidities in South Africans with systemic lupus erythematosus.

To investigate the prevalence and spectrum of comorbidities in South Africans with systemic lupus erythematosus (SLE). A nested case-control study of a known alive group (AG) and deceased group (DG) of 200 and 40 patients, respectively, matched for age and sex, attending a tertiary Lupus Clinic. Comorbidities that were documented included, but not restricted to, those listed in the Charlson comorbidity index (CCI). Lupus disease severity was assessed using the lupus severity index (LSI). Patients were mainly black female (94%), and the median age (IQR) and median disease duration (IQR) were 33 (25-42) and 6 (3-11) years, respectively. Overall, 191 (79.5%) patients experienced ≥ 1 comorbidities. The median (IQR) LSI and CCI scores were significantly higher in the DG than the AG (8.5 (6.7-9.1) vs 6.3 (5.2-8.3), p < 0.001 and 1 (1-3) vs 0 (0-2), p = 0.002, respectively). The commonest comorbidities were hypertension (42%), serious infections (36.6%) and tuberculosis (TB) (18.8%), the latter two being significantly more common in the DG (OR = 7.34, p < 0.0001 and OR = 3.40, p = 0.001, respectively). Of the CCI comorbidities, congestive cardiac failure (OR = 10.39, p = 0.0003), cerebrovascular disease (OR = 7.29, p = 0.01) and chronic kidney disease (OR = 3.08, p = 0.02) were more common in the DG. Both serious infections and TB were independent predictors of death. In this study of predominantly black South African SLE patients, comorbidities were common, with serious infections and TB amongst the commonest comorbidities. Unlike in industrialised Caucasian populations, cardiovascular comorbidities were rare in spite of a high prevalence of HPT.

Development and validation of a simple lupus severity index using ACR criteria for classification of SLE

ObjectiveTo develop a simple systemic lupus erythematosus (SLE) severity index that requires knowledge of only American College of Rheumatology (ACR) criteria and subcriteria.MethodsThis study used demographic, mortality and medical records...