Risk Factor For Lupus Nephritis Research Articles

Serum DNase1, sTNFR1 and sTNFR2 as Risk Factors for Lupus Nephritis in Systemic Lupus Erythematosus Patients

BACKGROUND: Early detection and management of lupus nephritis (LN) in systemic lupus erythematosus (SLE) are essential to prevent irreversible kidney damage and improve patient outcomes; therefore, identifying reliable biomarkers to predict LN is paramount. However, there are still relatively few studies examining the potential biomarkers for LN in SLE patients. This study was conducted to investigate serum deoxyribonuclease I (DNase), soluble tumor necrosing factor 1 (sTNFR1) and soluble tumor necrosing factor 2 (sTNFR2) as a risk factor for LN in SLE patients.METHODS: A case-control study involving SLE patients aged 20-60 years was conducted. Blood was withdrawn from each subject for the measurement of serum level of DNase1, sTNFR1, and sTNFR2 that was performed using enzyme-linked immunoassay (ELISA) methods. Data was then analyzed using Chi-Square test and logistic regression tests.RESULTS: A total of 22 patients with LN and 22 without LN were included. The cut-off value for DNase1, sTNFR1, and sTNFR2 were 5.05 ng/mL, 6.52 ng/mL, and 7.02 ng/mL, respectively. The risk factors of LN in SLE patients were the low level of serum DNase1 (aOR=6.64; 95%CI: 1.25-35.29; p=0.026), low level of serum sTNFR1 (aOR=8.12; 95% CI: 1.56-42.10; p=0.013), and low level of serum sTNFR2 (aOR=5.57; 95%CI: 1.03-30.11; p=0.046).CONCLUSION: Serum DNase1 lower than 5.05 ng/mL, sTNFR1 lower than 6.52 ng/mL, and sTNFR2 lower than 7.02 ng/mL were risk factors for lupus nephritis in SLE patients. Hence, serum DNase1, sTNFR1 and sTNFR2 could be used as risk factors predictors for LN in SLE patients.KEYWORDS: DNase1, sTNFR1, sTNFR2, SLE, lupus nephritis

Association of anti-C1q antibodies, adiponectin and HLA II genotype in Colombian patients with systemic lupus erythematosus with lupus nephritis

ObjectiveTo establish associations between the development of lupus nephritis (LN) and the expression of antibodies against C1q (anti-C1q) and serum adiponectin as these biomarkers have been previously postulated to be associated with the presence of LN. Materials and methodsA case–control study nested in a cohort was chosen. Patients with SLE with renal involvement were included. Measurement of antibodies against C1q, levels of adiponectin, and HLA expression DRB1 and DQB1 were evaluated. We searched for possible associations between the measured biomarkers and allelic HLA types found. ResultsOne hundred and six patients were recruited with LN with a mean age of 35 years. Mean adiponectin levels were 16.9μg/mL, and 60% of patients presented anti-C1q positivity. HLA DRB1*0404 and DRB1*1101 are protective factors for LN (OR: .42, p=.0030 and OR: 0.49, p=.046 respectively). HLA DRB1*0701 (OR: 3.15, p=.0452) and DRB1*0802 (OR: 8.3, p=.020) are susceptibility factors for LN. There was a tendency for association between anti-C1q positivity and high levels of adiponectin with type IV LN (OR 2.3 [95% CI: 0.68–8.2] and (OR: 2.67 [95% CI: .76–9.9] respectively). There was a tendency for association between anti-C1q positivity and HLA expression DRB1*0701 (OR 2.7 [95% CI: .81–11.5]), as well as high levels of adiponectin and HLA expression DRB1*0404 (OR 3.03 [95% CI: .92–12.8]). No association was found between anti-C1q and adiponectin with the expression of HLA DRB1*1501. There was positive correlation between levels of anti-C1q and the activity index in renal biopsy. ConclusionsIn the Colombian population there is a tendency for association of anti-C1q with the expression of HLA DRB1*07; however, the expression of other HLA II genes known as risk factors for LN, was not associated with the expression of anti-C1q, adiponectin or any specific type of LN.

Serum 25(OH)D levels are associated with disease activity and renal involvement in initial-onset childhood systemic lupus erythematosus.

Vitamin D deficiency is common in patients with systemic lupus erythematosus (SLE) and may affect their disease activity and severity. This study aims to assess the vitamin D status in patients with initial-onset SLE during childhood and its association with the clinical and laboratory markers of disease activity. This is a retrospective study that includes 168 patients with initial-onset SLE during childhood and 109 healthy children as controls. Clinical and laboratory data were recorded. The area under the curve (AUC) method was used to evaluate the efficacy of double-stranded deoxyribonucleic acid (dsDNA), lower 25(OH)D and complement 3 (C3) alone and in combination to diagnose the presence of renal damage in children with SLE. Compared with the controls (25.53 ± 7.02 ng/ml), patients with initial-onset SLE during childhood have lower serum 25(OH)D levels (18.63 ± 5.32 ng/ml) (P < 0.05). Among patients with initial-onset SLE during childhood, SLEDAI-2K scores are significantly higher in the vitamin D insufficiency (median = 14.5) and vitamin D deficiency (median = 14.0) groups than in the vitamin D sufficiency group (median = 9.0) (P < 0.05). Patients with initial-onset SLE during childhood with lower 25(OH)D levels are more likely to have lupus nephritis (LN) and a higher SDI score (P < 0.05). Compared with patients with other types of LN (16.69 ± 3.90 ng/ml), patients with type V LN have lower levels of 25(OH)D (12.27 ± 3.53 ng/ml) (P < 0.05). The AUC was 0.803 when dsDNA antibody, 25(OH)D level and C3 were used in combination to diagnose LN in patients with SLE. Vitamin D deficiency and insufficiency are closely related to an increase in SLEDAI and SDI scores. Significant decrease in vitamin D level is a risk factor for LN.

Analysis of risk factors and development of a nomogram prediction model for lupus nephritis in systemic lupus erythematosus patients

Background This study aimed to explore risk factors for lupus nephritis (LN) in systemic lupus erythematosus (SLE) patients and establish a Nomogram prediction model based on LASSO-logistic regression. Methods The clinical and laboratory data of SLE patients in Meishan People’s Hospital from July 2012 to December 2021 were analyzed retrospectively. All SLE patients were divided into two groups with or without LN. Risk factors were screened based on LASSO-logistic regression analysis, and a Nomogram prediction model was established. The receiver operating characteristic curve, calibration curves, and decision curve analysis were adopted to evaluate the performance of the Nomogram model. Results A total of 555 SLE patients were enrolled, including 303 SLE patients with LN and 252 SLE patients without LN. LASSO regression and multivariate logistic regression analyses showed that ESR, mucosal ulcer, proteinuria, and hematuria were independent risk factors for LN in SLE patients. The four clinical features were incorporated into the Nomogram prediction model. Results showed that calibration curve was basically close to the diagonal dotted line with slope 1 (ideal prediction case), which proved that the prediction ability of the model was acceptable. In addition, the decision curve analysis showed that the Nomogram prediction model could bring net clinical benefits to patients when the threshold probability was 0.12–0.54. Conclusion Four clinical indicators of ESR, mucosal ulcer, proteinuria, and hematuria were independent risk factors for LN in SLE patients. The predictive power of the Nomogram model based on LASSO-logistic regression was acceptable and could be used to guide clinical work.

Association of anti-C1q antibodies, adiponectin and HLA II genotype in Colombian patients with systemic lupus erythematosus with lupus nephritis

ObjectiveTo establish associations between the development of lupus nephritis (LN) and the expression of antibodies against C1q (anti-C1q) and serum adiponectin as these biomarkers have been previously postulated to be associated with the presence of LN. MethodologyA case–control study nested in a cohort was chosen. Patients with SLE with renal involvement were included. Measurement of antibodies against C1q, levels of adiponectin, and HLA expression DRB1 and DQB1 were evaluated. We searched for possible associations between the measured biomarkers and allelic HLA types found. ResultsOne hundred and six patients were recruited with LN with a mean age of 35 years. Mean adiponectin levels were 16.9μg/mL, and 60% of patients presented anti-C1q positivity. HLA DRB1*0404 and DRB1*1101 are protective factors for LN (OR: .42, p=.0030 and OR: 0.49, p=.046 respectively). HLA DRB1*0701 (OR: 3.15, p=.0452) and DRB1*0802 (OR: 8.3, p=.020) are susceptibility factors for LN. There was a tendency for association between anti-C1q positivity and high levels of adiponectin with type IV LN (OR 2.3 [95% CI: 0.68–8.2] and (OR: 2.67 [95% CI: .76–9.9] respectively). There was a tendency for association between anti-C1q positivity and HLA expression DRB1*0701 (OR 2.7 [95% CI: .81–11.5]), as well as high levels of adiponectin and HLA expression DRB1*0404 (OR 3.03 [95% CI: .92–12.8]). No association was found between anti-C1q and adiponectin with the expression of HLA DRB1*1501. There was positive correlation between levels of anti-C1q and the activity index in renal biopsy. ConclusionsIn the Colombian population there is a tendency for association of anti-C1q with the expression of HLA DRB1*07; however, the expression of other HLA II genes known as risk factors for LN, was not associated with the expression of anti-C1q, adiponectin or any specific type of LN.

The Influence of an Elastase-Sensitive Complement C5 Variant on Lupus Nephritis and Its Flare

IntroductionA C5 polymorphism (rs17611, 2404G>A) exists where the G allele associates with enhanced C5a-like production by neutrophil elastase. This cohort study investigated the influence of this polymorphism as a risk factor for lupus nephritis (LN), and on C5a and membrane attack complex (MAC) levels in LN during flare.MethodsA cohort of lupus patients (n = 155) was genotyped for the 2404G>A polymorphism. A longitudinal LN subset (n = 66) was tested for plasma and urine levels of C5a and MAC 4 and/or 2 months before and at nonrenal or LN flare.ResultsThe 2404G allele and 2404-GG genotype were associated with LN in black, but not white, lupus patients. In the longitudinal cohort, neither urine nor plasma C5a levels changed at nonrenal flare regardless of 2404G>A genotype or race. Urine (but not plasma) C5a levels increased at LN flare independent of race, more so in 2404-GG patients where 8 of 30 LN flares exhibited very high C5a levels. Higher proteinuria and serum creatinine levels also occurred in these eight flares. Urine (but not plasma) MAC levels also increased at LN flare in 2404-GG patients and correlated with urine C5a levels.ConclusionsThe C5 2404-G allele/GG genotype is a potential risk factor for LN uniquely in black lupus patients. The GG genotype is associated with sharp increases in urine C5a and MAC levels in a subset of LN flares that correspond to higher LN disease indices. The lack of corresponding changes in plasma suggests these increases reflect intrarenal complement activation.

Acute effects of air pollution on lupus nephritis in patients with systemic lupus erythematosus: A multicenter panel study in China

Air pollution may trigger systemic lupus erythematosus (SLE). However, few studies have investigated the associations between air pollution and complications of SLE, such as lupus nephritis (LN). In this study, multicenter longitudinal data from 13 hospitals in China, including 8552 SLE patients with 24,762 visits, were used. Based on the generalized estimating equation (GEE) model, we assessed the associations of LN occurrence with short-term exposures to different air pollutants including particulate matter with an aerodynamic diameter < 2.5 μm (PM2.5), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3). We identified 2672 LN patients, and about half of them were from east China. Our results based on the entire data set showed that PM2.5 and NO2 were risk factors for LN within one month after exposure, with odds ratio of 1.16 (95% confidence interval (CI), 1.08–1.19) at lag 18 day and 1.19 (95% CI, 1.12–1.26) at lag 16 day relative to an interquartile range (IQR) increase in PM2.5 and NO2, respectively. This positive association between LN and NO2 was also observed for south, west, and east China. In addition, we found that the short term exposure to CO and O3 was not generally associated with LN. Finally, the negative associations of LN with SO2 were found for the entire region and east China. Our results implied that SLE patients may gain the health benefits of air quality improvement in China. Our work also provided evidence that short-term variations in air pollution may trigger LN, and further studies are needed to confirm these findings and the potential pathogenic mechanisms should be explored.

Interferon regulatory factor (5) Gene Variants (rs2004640) as Genetic Risk Factor for Systemic Lupus Erythematosus but not Lupus Nephritis in Egyptian adults

Systemic lupus erythematosus (SLE) is an autoimmune disease with complex etiology. Systemic lupus erythematosus (SLE) is an autoimmune disease with complex etiology. Genetic aberrations disrupting the immune regulatory mechanisms may initiate autoimmune disease development. Recent studies have proved that the interferon regulatory factor 5 (IRF5) gene is an important risk factor for SLE. We aimed to investigate the association of the rs2004640 polymorphism within the IRF5 gene with SLE and lupus Nephritis and SLE activity in a sample of adult Egyptian population. 199 individuals were classified into: group I: included 118 patients who were further subdivided into 57 patients with and 61 patients without lupus nephritis respectively and group II: 81 healthy subjects as controls. Genotyping of the SNP rs2004640 at IRF5 gene was analyzed via allele discrimination assay using Real-Time PCR. TT genotype was the most abundant among SLE patients (p=0.001), but GG genotype was the most abundant in controls (p=0.001) while, genotype frequency showed no significant statistical difference between lupus patients with and without nephritis (p= 0.2, 0.1 respectively). The multivariate analysis of prediction of SLE activity [assessed by systemic lupus erythematosus disease activity index (SLEDAI) scoring] showed that the protein/creatinine ratio (95% CI, 0.001 to 0.002) and anti-dsDNA (95% CI, 0.005 to 0.1) were independent factors of SLE activity (OR=0.001 and 0.008 respectively). IRF5 gene polymorphism (rs2004640) might be candidate risk factor for developing SLE but not risk factor for lupus nephritis or the disease activity in a sample of adult Egyptian population.

Association of ficolin-2 gene polymorphisms and susceptibility to systemic lupus erythematosus in Egyptian children and adolescents: a multicenter study.

Pediatric-onset SLE (pSLE) is a multisystem autoimmune disease. Recently, the ficolin-2 (FCN2) gene has emerged as a potential candidate gene for susceptibility to SLE. The objective of this study was to evaluate the association of the FCN2 gene polymorphisms at positions -986 (G/A), -602 (G/A), -4 (A/G) and SNP C/T (rs3124954) located in intron 1, with susceptibility to pSLE in Egyptian children and adolescents. This was a multicenter study of 280 patients diagnosed with pSLE, and 280 well-matched healthy controls. The FCN2 promoter polymorphisms at -986 G/A (rs3124952), -602 G/A (rs3124953), -4 A/G (rs17514136) and SNP C/T (rs3124954) located in intron 1 were genotyped by polymerase chain reaction, while serum ficolin-2 levels were assessed using enzyme-linked immunosorbent assay. The frequencies of the FCN2 GG genotype and G allele at -986 and -602 positions were significantly more represented in patients with pSLE than in controls (p < 0.001). Conversely, the FCN2 AA genotype and A allele at position -4 were more common in patients than in controls (p < 0.001). Moreover, patients carrying the FCN2 GG genotype in -986 position were more likely to develop lupus nephritis (odds ratio: 2.6 (95% confidence interval: 1.4-4.78); p = 0.006). The FCN2 AA genotype at position -4 was also identified as a possible risk factor for lupus nephritis (odds ratio: 3.12 (95% confidence interval: 1.25-7.84); p = 0.024). The FCN2 promoter polymorphisms may contribute to susceptibility to pSLE in Egyptian children and adolescents. Moreover, the FCN2 GG genotype at position -986 and AA genotype at position -4 were associated with low serum ficolin-2 levels and may constitute risk factors for lupus nephritis in pSLE.

GATA3 rs3824662 gene polymorphism as possible risk factor for systemic lupus erythematosus.

There is no report about the association between GATA3 rs3824662 polymorphism and systemic lupus erythematosus (SLE). To investigate the possible role of GATA3 rs3824662 polymorphism as a susceptibility risk factor for either adult SLE (aSLE) or pediatric SLE (pSLE) and to evaluate its role in the development of lupus nephritis (LN) in pSLE. Typing of GATA3 rs3824662 polymorphism was done using real-time polymerase chain reaction for three groups; 104 pSLE patients, 140 aSLE patients and 436 age- and sex-matched healthy controls. Non-significant differences were found between SLE patients and healthy controls for the allele and genotype frequencies of GATA3 rs3824662 ( p > 0.05). In pSLE; the AC genotype was associated with LN ( p = 0.04); the A allele and AC genotype were associated with persistent proteinuria ( p = 0.036 and 0.01, respectively) and both the A allele and AA genotype were associated with higher chronicity index ( p = 0.031 and 0.04, respectively). In aSLE; the C allele was associated with cellular cast ( p = 0.03) and thrombocytopenia ( p = 0.01). Logistic regression analysis revealed significant association between the AC+AA genotypes and the prediction of LN and renal active disease in pSLE ( p = 0.04 and 0.01, respectively). GATA3 rs3824662 is not associated with susceptibility to SLE either in adult or in pediatric patients; however, in pSLE patients, the heterozygous AC genotype could be considered a risk factor for LN. At the same time, the AC and AA genotypes could be considered as predictors for LN and active renal disease. However, the small sample size is a limiting factor of the present study when interpreting the positive association.

Interferon-\u03bb3/4 genetic variants and interferon-\u03bb3 serum levels are biomarkers of lupus nephritis and disease activity in Taiwanese

BackgroundType III interferons (IFNs) or IFN-λs are the newly discovered cytokines that primarily target the cells of epithelial and myeloid lineages, which are major components of kidneys. The current study aimed to investigate whether IFN-λs are involved in the pathogenesis of systemic lupus erythematosus (SLE) and lupus nephritis.MethodsTaqMan allele discrimination assays were used to determine IFNL3/4 SNP genotypes of 1620 healthy controls and 1013 SLE patients (two independent cohorts consisting of 831 and 182 subjects, respectively) from Taiwan. The distributions of IFNL3/4 SNP genotypes and allele frequencies were compared between SLE patients and healthy controls and among SLE patients stratified by clinical phenotypes. ELISA was used to determine the serum IFN-λ3 concentrations of SLE patients.ResultsAll major IFN3/4 SNP alleles were significantly associated with the risk for lupus nephritis (rs8099917T, PFDR = 0.0021, OR 1.75, 95% CI 1.24–2.47; rs12979860C, PFDR = 0.0034, OR 1.65, 95% CI 1.18–2.30; rs4803217C, PFDR = 0.0021, OR 1.76, 95% CI 1.25–2.48; and ss469415590TT, PFDR = 0.0021, OR 1.73, 95% CI 1.23–2.42) among SLE patients. Similarly, the major IFNL3/4 SNP haplotype rs8099917T-ss469415590TT-rs12979860C-rs4803217C (or T-TT-C-C) was a significant risk factor for lupus nephritis (P = 0.0015, OR 1.68, 95% CI 1.22–2.32). Additionally, all minor IFN3/4 SNP alleles were significantly associated with SLE susceptibility in nephritis-negative SLE patients as compared to normal healthy controls (rs8099917G, PFDR = 0.00177, OR 1.68, 95% CI 1.24–2.28; rs12979860T, PFDR = 0.00299, OR 1.58, 95% CI 1.18–2.32; rs4803217A, PFDR = 0.00176, OR 1.65, 95% CI 1.22–2.23; and ss469415590ΔG, PFDR = 0.00176, OR 1.70, 95% CI 1.26–2.29). Furthermore, the elevated serum levels of IFN-λ3 were significantly correlated with the complement depression and the high SLE disease activities in SLE patients.ConclusionsIFN-λ3/4 genetic variants play a unique role in the development of lupus nephritis and SLE.

Low copy number of FCGR3B is associated with lupus nephritis in a Chinese population.

Lupus nephritis (LN) is a polygenic disease caused by an interaction between hereditary and environmental factors. Numerous gene copy number variations have been identified to contribute to this disease. Previously, immunoglobulin (Ig)G Fcγ receptor 3B (FCGR3B) copy number variation (CNV) was reported to be associated with LN in the Caucasian population. However, the effect of FCGR3B CNV on LN in the Chinese population remains unknown. The present study aimed to investigate whether CNVs of FCGR3B are associated with LN in the Henan Chinese population. FCGR3B CNVs were determined in 142 LN patients and 328 healthy controls. A modified methodology based on competitive polymerase chain reaction, a Multiplex AccuCopy™ kit was used to detect FCGR3B copy number. Clinical and laboratory data was collected retrospectively from medical records. To evaluate associations between FCGR3B CNVs and LN susceptibility, the present study calculated the odds ratios using a logistic regression analysis. The current study identified that the distribution of FCGR3B copy number was significantly different between LN and healthy controls (P=0.031). A low copy number (<2) of FCGR3B was significantly enriched in LN patients (P=0.042), and was a risk factor for LN (odds ratio=2.059; 95% confidence interval, 1.081-3.921; P=0.028). However, a high copy number (>2) had no effect on LN. There were no associations between FCGR3B CNV and clinical phenotypes of LN. The results from the present study demonstrate that a low copy number of FCGR3B is a risk factor for LN in a Chinese population.

Association of the osteopontin rs1126616 polymorphism and a higher serum osteopontin level with lupus nephritis.

Osteopontin (OPN) is a chemokine-like glycoprotein that has a prominent role in regulating inflammation and immunity. OPN polymorphisms and elevated OPN levels are associated with systemic lupus erythematosus (SLE) in several populations. The aim of present study was to evaluate the association between the OPN rs1126616 polymorphism and OPN level with SLE susceptibility. A total of 163 SLE patients and 180 age-, gender- and ethnically matched controls were genotyped for the rs1126616 polymorphism by the polymerase chain reaction-restriction fragment length polymorphism method. Serum OPN levels were assayed by the enzyme-linked immunosorbent assay. There was no association between the OPN rs1126616 C/T polymorphism and SLE. The frequency of the OPN rs1126616 CT genotype was significantly higher in SLE patients with nephritis compared to SLE patients without nephritis and controls. Additionally, the frequency of TT genotypes was higher in SLE patients with nephritis compared to controls. The serum OPN levels were significantly higher in SLE patients compared to controls (50.6±22 vs. 35.6±15.8 ng/ml, P<0.001). Increased serum OPN levels were observed in SLE patients with lupus nephritis and joint symptoms. There was no correlation between OPN levels and the OPN rs1126616 polymorphism. The present data suggest that the CT and TT genotypes of the OPN rs1126616 polymorphism could be a risk factor for lupus nephritis. The OPN level is associated with SLE and certain SLE manifestations. However, there was no association between the OPN rs1126616 C/T polymorphism and SLE susceptibility.

Association of rs172378 C1q gene cluster polymorphism with lupus nephritis in Bulgarian patients.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that can affect substantially any organ in the body. One of its most severe manifestations is lupus nephritis. Hereditary C1q deficiency is strongly related to SLE but there are very few and inconsistent studies exploring the single nucleotide polymorphisms (SNPs) of the C1q gene cluster in relation to the pathogenesis of SLE. In the present study we evaluated the possible association of gene variants in complement C1q gene cluster with susceptibility to lupus nephritis in a Bulgarian population, focusing on five previously associated with SLE SNPs in other populations. Thirty-eight patients with lupus nephritis and 185 healthy controls, all from Bulgaria, were genotyped for the five C1q SNPs, rs587585, rs292001, rs172378, rs294179 and rs631090, by quantitive real-time PCR methods. We also determined C1q serum levels of C1q and haemolytic activity of C1q in relation to C1q genotypes. Lupus nephritis patients and healthy controls had statistically similar frequencies of genotypes and alleles of rs587585, rs292001, rs294179 and rs631090 SNPs. Nevertheless, minor G allele in rs172378 was significantly overrepresented in lupus nephritis patients when compared with healthy controls (36% vs. 23%, odds ratio = 1.80, 95% confidence interval = 1.06-3.06, p = 0.029). The SNP rs292001 showed a trend towards lower serum C1q levels in healthy controls. Two SNPs - rs294179 and rs292001 - were in a linkage disequilibrium in patients and healthy controls with different power (healthy controls: r (2 )= 0.6526, D' = 0.842; lupus nephritis patients: r (2 )= 0.491, D' = 0.686). The haplotype C-A-A-T-T in the patient group was associated with lupus nephritis: 7.7% vs. 0.8%, odds ratio = 10.81, 95% confidence interval = 1.45-80.57, p = 0.002. These results support the implication of the G allele in rs172378 as a risk factor for lupus nephritis in a homozygous status, at least for a Bulgarian population.

Association of programmed cell death 1 polymorphisms and systemic lupus erythematosus: a meta-analysis

Programmed cell death 1 (PDCD1 or PD1) polymorphisms have been inconsistently reported to be associated with systemic lupus erythematosus (SLE). The aim of this study was to explore whether the PDCD1 polymorphisms confer a susceptibility to SLE and lupus nephritis (LN). We conducted a meta-analysis on the association of PDCD1 polymorphisms with SLE in overall and specific ethnic populations. A total of 15 separate comparisons were included in this meta-analysis consisting of nine Europeans, two Latin Americans, two Africans, one Asian and one unknown participant. In subgroup analysis, the PD1.3A allele was significantly associated with SLE in Latin Americans (OR = 3.073, 95% CI = 1.416-6.461, P = 0.003), but not in patients of European and African decent. The PD1.3A allele was a risk factor for LN in European descendants (OR = 2.207, 95% CI = 1.488-3.467, P < 0.001). The PD1.5C allele was a risk factor for SLE in Europeans (OR = 1.297, 95% CI = 1.024-1.643, P = 0.031). In conclusion, this meta-analysis demonstrated an association of the PD1.3A allele with LN in European and SLE in Latin-American populations. Furthermore, the PD1.5C allele was associated with SLE susceptibility in Europeans.

Ethnic, clinical and immunological factors in systemic lupus erythematosus and the development of lupus nephritis: results from a multi-ethnic New Zealand cohort

The aim of this study was to identify risk factors for lupus nephritis including clinical, laboratory, and ethnic factors in a cohort of lupus patients in New Zealand. A retrospective study of patients from two teaching hospitals in Auckland, New Zealand. Patients were selected if they had attended as either an inpatient, or a rheumatology outpatient between 2000 and 2005. 170 patients had SLE according to ACR classification. Lupus nephritis (LN) was diagnosed according to ACR criteria. Clinical, laboratory, and ethnic data were gathered from the patient notes. Twenty-four patients had LN at diagnosis and 32 patients developed LN after diagnosis. LN was associated with serositis (P = 0.008), cutaneous vasculitis (P = 0.026), anaemia (P = 0.005), CRP elevation >6 months (P < 0.001), hypocomplementaemia >6 months (P < 0.0001). Patients with elevated doublestranded DNA (dsDNA) (>5 x normal) were more likely to develop type IV LN (P = 0.0096). Forty-one percent of patients were Caucasian, 12% Maori, 23% Pacific People, 16% Asian, 6% Indian. Maori patients with SLE (odds ratio (OR) = 8.47, 95% confidence interval (CI) = 2.11-33.96, P = 0.002), and Pacific People (OR = 3.11, 95% CI = 1.29-11.48, P = 0.014) had increased risk for developing LN. Anaemia at presentation (hazard ratio (HR) 3.2, 95% CI = 1.4-7.1, P = 0.004), and low complement >6 months (HR = 3.4, 95% CI = 1.4-8.7, P = 0.008) were independent risk factors for developing LN after SLE diagnosis. In New Zealand, Pacific People and Maori patients with SLE have a higher incidence of LN, and patients with anaemia and hypocomplementaemia are more likely to develop LN after diagnosis. Patients with high dsDNA levels are more likely to develop Type IV lupus nephritis.

Systemic lupus erythematosus in three ethnic groups. XII. Risk factors for lupus nephritis after diagnosis.

The purpose of this study was to determine the cumulative incidence of lupus nephritis (LN) and the factors predictive of its occurrence in a multiethnic systemic lupus erythematosus (SLE) cohort. We studied 353 SLE patients as defined by the American College of Rheumatology (ACR) criteria (65 Hispanics, 93 African-Americans and 91 Caucasians). First, we determined the cumulative incidence of LN in all patients. Next, we determined the predictors for LN in those with nephritis occurring after diagnosis. The dependent variable, LN, was defined by: (1) A renal biopsy demonstrating World Health Organization (WHO), class II-V histopathology; and/or (2) proteinuria > or = 0.5 g/24 h or 3+ proteinuria attributable to SLE; and/or (3) one of the following features also attributable to SLE and present on two or more visits, which were performed at least 6 months apart--proteinuria > or = 2+, serum creatinine > or = 1.4 mg/dl, creatinine clearance < or = 79 ml/min, > or = 10 RBCs or WBCs per high power field (hpf), or > or = 3 granular or cellular casts per hpf. Independent variables assessed at diagnosis, and if absent, at baseline, were from four domains: sociodemographic, clinical, immunologic and immunogenetic (including the complete antibody profile and MHC class II alleles), and health habits. Variables with P < 0.05 by chi square analyses were entered into domain-specific stepwise logistic regression analyses controlling for disease duration, with LN as the dependent variable. Significant domain-specific regression variables (P < or = 0.1) were then entered into an overall model. The cumulative incidence of LN was 54.3% in all patients, and 35.3% for those developing LN after diagnosis. LN after diagnosis occurred in 43.1% of 65 Hispanics, 50.5% of 93 African-Americans, and 14.3% of 91 Caucasians, P < 0.0001. The duration of follow-up for those with LN after diagnosis was 5.5+/-2.4 vs 4.0+/-2.9 years for those without LN. Hispanic (odds ratio (OR) = 2.71, 95% confidence limits (CL) = 1.07-6.87, P < 0.04) and African-American ethnicities (OR = 3.13, 95% CL = 1.21-8.09, P < 0.02), not married or living together (OR = 3.45, 95% CL = 1.69-7.69, P < 0.0003), higher SLAM score (OR = 1.11, 95% CL = 1.02-1.19, P < 0.007), anti-dsDNA (OR = 3.14, 95% CL = 1.50-6.57, P < 0.0001) and anti-RNP (OR = 4.24, CL = 1.98-9.07, P < 0.0001) antibodies were shown to be significant predictors of the occurrence of LN. Repeated analyses excluding the patients with missing HLA data showed that absence of HLA-DQB1*0201 was also a significant predictor for the occurrence of LN (OR = 2.34, CL = 1.13-5.26, P < 0.04). In conclusion, LN occurred significantly more often in Hispanics and African-Americans with SLE. Sociodemographic, clinical and immunologic/immunogenetic factors seem to be predictive of LN occurring after the diagnosis of SLE has been made.

Fc gamma RIIA alleles are heritable risk factors for lupus nephritis in African Americans.

Allelic variants of Fc gamma R confer distinct phagocytic capacities providing a mechanism for heritable susceptibility to immune complex disease. Human Fc gamma RIIa has two codominantly expressed alleles, R131 and H131, which differ substantially in their ability to ligate human IgG2. The Fc gamma RIIa-H131 is the only human Fc gamma R which recognizes IgG2 efficiently and optimal IgG2 handling occurs only in the homozygous state. Therefore, since immune complex clearance is essential in SLE, we hypothesized that Fc gamma RIIA genes are important disease susceptibility factors for SLE, particularly lupus nephritis. In a two-stage cross-sectional study, we compared the distribution of Fc gamma RIIA alleles in African Americans with SLE to that in African American non-SLE controls. A pilot study of 43 SLE patients and 39 controls demonstrated a skewed distribution of Fc gamma RIIA alleles, with only 9% of SLE patients homozygous for Fc gamma RIIa-H131 compared with 36% of controls (odds ratio, 0.18; 95% CI, 0.05-0.69, P = 0.009). This was confirmed with a multicenter study of 214 SLE patients and 100 non-SLE controls. The altered distribution of Fc gamma RIIA alleles was most striking in lupus nephritis. Trend analysis of the genotype distribution showed a highly significant decrease in Fc gamma RIIA-H131 as the likelihood for lupus nephritis increased (P = 0.0004) consistent with a protective effect of the Fc gamma RIIA-H131 gene. The skewing in the distribution of Fc gamma RIIA alleles identifies this gene as a risk factor with pathophysiologic importance for the SLE diathesis in African Americans.