To evaluate the expression of Th1, Th2, and Th17 cytokines in patients with systemic lupus erythe... more To evaluate the expression of Th1, Th2, and Th17 cytokines in patients with systemic lupus erythematosus (SLE), and verify the association between serum cytokine levels and vitamin D concentration. The sample consisted of 172 patients with SLE. 25-Hydroxyvitamin D (25(OH)D) levels were measured by chemiluminescence and 25(OH)D levels <20 ng/mL were considered to reflect vitamin D deficiency. Serum cytokine levels were measured in once-thawed samples, using a Th1/Th2/Th17 CBA (cytometric beads array) kit. One hundred and sixty-one (93.6%) patients were women and 128 (74.4%) were of European descent. Mean patient age was 40.5 ± 13.8 years, and mean age at diagnosis was 31.5 ± 13.4 years. At the time of study entry, patients had a median (IQR) SLEDAI of 2 (1-4) and SLICC of 0 (0-1). Mean 25(OH)D concentration was 25.4 ± 11.04 ng/mL. Fifty-nine (34.3%) patients had a vitamin D deficiency. No statistically significant associations were identified between cytokine and vitamin D levels. The most significant finding was a positive correlation between INF-α levels and SLEDAI (rs = 0.22, p = 0.04). Although vitamin D deficiencies are highly prevalent in patients with SLE, vitamin D levels were not significantly associated with patient cytokine profiles. The positive correlation between IFN-α levels and SLEDAI showed in this study corroborates other findings in the literature. The present results did not replicate those of in vitro studies of the effect of vitamin D levels on cytokine profiles. Placebo-controlled intervention trials of the effect of vitamin D on cytokine profiles are still required before any definitive conclusions can be drawn regarding the association between these variables.
Background: FM increases DAS28, SDAI and CDAI, misleading DMARD use and increasing costs and adve... more Background: FM increases DAS28, SDAI and CDAI, misleading DMARD use and increasing costs and adverse events. (1,2) Seven-joint PDUS score is an objective measure of RA activity and, therefore, should not be influenced by FM.
ABSTRACT Background Systemic lupus erythematosus (SLE) is a multisystem inflammatory autoimmune d... more ABSTRACT Background Systemic lupus erythematosus (SLE) is a multisystem inflammatory autoimmune disease with higher prevalence among women [1]. The first manifestation of SLE occurs most commonly at childbearing age, but can appear at any age [2]. Previous studies demonstrated heterogeneous clinical presentation, medication use and disease severity among different onset age groups [3]. The influence of age at disease onset on the clinical presentation and prognosis remains not well recognized. Objectives The present study aims to evaluate differences in clinical and laboratory manifestations and medication use in each SLE patient group according age of onset disease. Methods This cross-sectional study consisted of 549 patients with SLE who attended the Rheumatology Clinic of the Hospital de Clínicas de Porto Alegre between 2003 and 2013. Interview during medical consultation and medical chart review were used to collect demographic, clinical and laboratory data. The patients were classified into three groups according to their ages at disease diagnosis. Results Among the 549 patients studied, 54 (9.8%) were Juvenile-onset (≤16 years), 427 (77.8%) were Adult-onset (>16 and <50 years) and 68 (12.4%) were Late-onset (≥50 years). The frequency of women was higher in Adult-onset (93.9%) than in Juvenile-onset (83.3%) (p=0.003). Arthritis was predominantly found in Adult-onset group (79.1%) when compared with Late-onset (61.8%) (p=0.006). Nephritis was more common in Juvenile-onset (66.7%) than in Late-onset (27.9%) (p<0.001), as also occurred with positive results for anti-DNA (64.2% vs. 38.1%, respectively). A non-significantly difference of Sjögren's syndrome, antiphospholipid syndrome, concomitant autoimmune disease and family history of SLE was observed among the groups. Disease activity index and damage scores were similar among the groups. The Juvenile-onset was more likely to require oral corticosteroids (p=0.01), pulse methylprednisolone (p<0.001), cyclophosphamide (p<0.001), azathioprine (p<0.001) and mycophenolate mofetil (p<0.001) in the treatment and maintenance of SLE than the other two groups. In contrast, the Late-onset had used more commonly hydroxychloroquine than the Juvenile-onset (98.5% vs. 90.6%, respectively) (p=0.04). Conclusions Our findings confirm most of the data previously published. The juvenile-onset group showed a more severe disease due to the higher incidence of nephritis and the need of a more aggressive treatment with immunosuppressive drugs. The rate of women is bigger in the adult-onset group, which can be explained by the hormonal effect of estrogen. References Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.4193
The mannose-binding lectin gene (MBL-2) has emerged as a candidate for systemic lupus erythematos... more The mannose-binding lectin gene (MBL-2) has emerged as a candidate for systemic lupus erythematosus susceptibility, but studies in Brazilian population have not been conducted. To examine potential associations of mannose-binding lectin alleles G57E, G54D, IVSnt5, R52C and R52H with susceptibility to and clinical expression of systemic lupus erythematosus in southern Brazilian patients, we conducted a case-control study with 327 consecutive patients with diagnosis of systemic lupus erythematosus and 345 healthy controls. Genotyping was performed by restriction fragment length polymorphism-polymerase chain reaction assay. A statistically significant difference in the frequencies of allele R52C was observed in European-derived systemic lupus erythematosus patients when compared with controls (9.6% vs. 3.3%, p < 0.001, odds ratio: 3.15, 95% confidence interval: 1.76-5.62, p < 0.05). The frequencies of alleles G54D and G57E were not different between European-derived systemic lupus erythematosus patients and controls. There were no differences between clinical and laboratory features in systemic lupus erythematosus patients according to the presence or absence of mannose-binding lectin allelic variants. These results support an increased risk of systemic lupus erythematosus in European-derived individuals carrying allele R52C. Patients carrying this allele have an approximately three-fold higher odds ratio of developing systemic lupus erythematosus when compared with controls. Our data do not support associations between the mannose-binding lectin allelic variants studied and clinical expression of systemic lupus erythematosus. Lupus (2010) 19, 280-287.
Human leukocyte antigen-G (HLA-G) is a nonclassical class I major histocompatibility complex mole... more Human leukocyte antigen-G (HLA-G) is a nonclassical class I major histocompatibility complex molecule which is induced at the course of inflammatory pathologies, and its expression has been suggested as a possible mechanism of tissue protection against autoimmune inflammatory responses, therefore acting as a mechanism of immune surveillance. We investigated the influence of the 14 bp polymorphism of the HLA-G gene on systemic lupus erythematosus (SLE) by analyzing 293 patients with SLE and 460 healthy controls. The patient's group was not in Hardy-Weinberg equilibrium, presenting an excess of heterozygotes (P = 0.014). The heterozygote group exhibited lower systemic lupus erythematosus disease activity indexes than the homozygous deletion group and the homozygous insertion group (mean value = 2.29 against 2.97 and 3.4, respectively, P = 0.035). Photosensitive patients showed a higher frequency of heterozygotes and an equivalent lower frequency of homozygotes for deletion; on the other hand, patients without arthritis presented a higher frequency of heterozygotes than the arthritis group and also a lower frequency of the del/del genotype. Overall, our results support the idea of a role of the HLA-G insertion/deletion polymorphism and therefore a role for the HLA-G molecule, on the pathology of SLE. Lupus (2009) 18, 424-430.
To evaluate the expression of Th1, Th2, and Th17 cytokines in patients with systemic lupus erythe... more To evaluate the expression of Th1, Th2, and Th17 cytokines in patients with systemic lupus erythematosus (SLE), and verify the association between serum cytokine levels and vitamin D concentration. The sample consisted of 172 patients with SLE. 25-Hydroxyvitamin D (25(OH)D) levels were measured by chemiluminescence and 25(OH)D levels &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;20 ng/mL were considered to reflect vitamin D deficiency. Serum cytokine levels were measured in once-thawed samples, using a Th1/Th2/Th17 CBA (cytometric beads array) kit. One hundred and sixty-one (93.6%) patients were women and 128 (74.4%) were of European descent. Mean patient age was 40.5 ± 13.8 years, and mean age at diagnosis was 31.5 ± 13.4 years. At the time of study entry, patients had a median (IQR) SLEDAI of 2 (1-4) and SLICC of 0 (0-1). Mean 25(OH)D concentration was 25.4 ± 11.04 ng/mL. Fifty-nine (34.3%) patients had a vitamin D deficiency. No statistically significant associations were identified between cytokine and vitamin D levels. The most significant finding was a positive correlation between INF-α levels and SLEDAI (rs = 0.22, p = 0.04). Although vitamin D deficiencies are highly prevalent in patients with SLE, vitamin D levels were not significantly associated with patient cytokine profiles. The positive correlation between IFN-α levels and SLEDAI showed in this study corroborates other findings in the literature. The present results did not replicate those of in vitro studies of the effect of vitamin D levels on cytokine profiles. Placebo-controlled intervention trials of the effect of vitamin D on cytokine profiles are still required before any definitive conclusions can be drawn regarding the association between these variables.
Background: FM increases DAS28, SDAI and CDAI, misleading DMARD use and increasing costs and adve... more Background: FM increases DAS28, SDAI and CDAI, misleading DMARD use and increasing costs and adverse events. (1,2) Seven-joint PDUS score is an objective measure of RA activity and, therefore, should not be influenced by FM.
ABSTRACT Background Systemic lupus erythematosus (SLE) is a multisystem inflammatory autoimmune d... more ABSTRACT Background Systemic lupus erythematosus (SLE) is a multisystem inflammatory autoimmune disease with higher prevalence among women [1]. The first manifestation of SLE occurs most commonly at childbearing age, but can appear at any age [2]. Previous studies demonstrated heterogeneous clinical presentation, medication use and disease severity among different onset age groups [3]. The influence of age at disease onset on the clinical presentation and prognosis remains not well recognized. Objectives The present study aims to evaluate differences in clinical and laboratory manifestations and medication use in each SLE patient group according age of onset disease. Methods This cross-sectional study consisted of 549 patients with SLE who attended the Rheumatology Clinic of the Hospital de Clínicas de Porto Alegre between 2003 and 2013. Interview during medical consultation and medical chart review were used to collect demographic, clinical and laboratory data. The patients were classified into three groups according to their ages at disease diagnosis. Results Among the 549 patients studied, 54 (9.8%) were Juvenile-onset (≤16 years), 427 (77.8%) were Adult-onset (&gt;16 and &lt;50 years) and 68 (12.4%) were Late-onset (≥50 years). The frequency of women was higher in Adult-onset (93.9%) than in Juvenile-onset (83.3%) (p=0.003). Arthritis was predominantly found in Adult-onset group (79.1%) when compared with Late-onset (61.8%) (p=0.006). Nephritis was more common in Juvenile-onset (66.7%) than in Late-onset (27.9%) (p&lt;0.001), as also occurred with positive results for anti-DNA (64.2% vs. 38.1%, respectively). A non-significantly difference of Sjögren&#39;s syndrome, antiphospholipid syndrome, concomitant autoimmune disease and family history of SLE was observed among the groups. Disease activity index and damage scores were similar among the groups. The Juvenile-onset was more likely to require oral corticosteroids (p=0.01), pulse methylprednisolone (p&lt;0.001), cyclophosphamide (p&lt;0.001), azathioprine (p&lt;0.001) and mycophenolate mofetil (p&lt;0.001) in the treatment and maintenance of SLE than the other two groups. In contrast, the Late-onset had used more commonly hydroxychloroquine than the Juvenile-onset (98.5% vs. 90.6%, respectively) (p=0.04). Conclusions Our findings confirm most of the data previously published. The juvenile-onset group showed a more severe disease due to the higher incidence of nephritis and the need of a more aggressive treatment with immunosuppressive drugs. The rate of women is bigger in the adult-onset group, which can be explained by the hormonal effect of estrogen. References Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.4193
The mannose-binding lectin gene (MBL-2) has emerged as a candidate for systemic lupus erythematos... more The mannose-binding lectin gene (MBL-2) has emerged as a candidate for systemic lupus erythematosus susceptibility, but studies in Brazilian population have not been conducted. To examine potential associations of mannose-binding lectin alleles G57E, G54D, IVSnt5, R52C and R52H with susceptibility to and clinical expression of systemic lupus erythematosus in southern Brazilian patients, we conducted a case-control study with 327 consecutive patients with diagnosis of systemic lupus erythematosus and 345 healthy controls. Genotyping was performed by restriction fragment length polymorphism-polymerase chain reaction assay. A statistically significant difference in the frequencies of allele R52C was observed in European-derived systemic lupus erythematosus patients when compared with controls (9.6% vs. 3.3%, p < 0.001, odds ratio: 3.15, 95% confidence interval: 1.76-5.62, p < 0.05). The frequencies of alleles G54D and G57E were not different between European-derived systemic lupus erythematosus patients and controls. There were no differences between clinical and laboratory features in systemic lupus erythematosus patients according to the presence or absence of mannose-binding lectin allelic variants. These results support an increased risk of systemic lupus erythematosus in European-derived individuals carrying allele R52C. Patients carrying this allele have an approximately three-fold higher odds ratio of developing systemic lupus erythematosus when compared with controls. Our data do not support associations between the mannose-binding lectin allelic variants studied and clinical expression of systemic lupus erythematosus. Lupus (2010) 19, 280-287.
Human leukocyte antigen-G (HLA-G) is a nonclassical class I major histocompatibility complex mole... more Human leukocyte antigen-G (HLA-G) is a nonclassical class I major histocompatibility complex molecule which is induced at the course of inflammatory pathologies, and its expression has been suggested as a possible mechanism of tissue protection against autoimmune inflammatory responses, therefore acting as a mechanism of immune surveillance. We investigated the influence of the 14 bp polymorphism of the HLA-G gene on systemic lupus erythematosus (SLE) by analyzing 293 patients with SLE and 460 healthy controls. The patient's group was not in Hardy-Weinberg equilibrium, presenting an excess of heterozygotes (P = 0.014). The heterozygote group exhibited lower systemic lupus erythematosus disease activity indexes than the homozygous deletion group and the homozygous insertion group (mean value = 2.29 against 2.97 and 3.4, respectively, P = 0.035). Photosensitive patients showed a higher frequency of heterozygotes and an equivalent lower frequency of homozygotes for deletion; on the other hand, patients without arthritis presented a higher frequency of heterozygotes than the arthritis group and also a lower frequency of the del/del genotype. Overall, our results support the idea of a role of the HLA-G insertion/deletion polymorphism and therefore a role for the HLA-G molecule, on the pathology of SLE. Lupus (2009) 18, 424-430.
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