Increased myeloperoxidase plasma levels in rheumatoid arthritis.

High myeloperoxidase (MPO) serum levels have been shown in several inflammatory diseases, including rheumatoid arthritis (RA). However, the correlation between MPO levels and disease activity in RA patients is still controversial. The aim of the study was to determine MPO plasma levels in RA patients and to investigate potential correlations between MPO levels and disease activity and treatment. MPO plasma levels were measured by ELISA according the manufacturer's instructions. Disease activity was measured by DAS28 ESR and DAS28 CRP scores, and patients were classified into 4 groups: group 1 DAS28 < 2.6; group 2: 2.6 ≤ DAS28 ≤ 3.2; group 3: 3.2 < DAS28 ≤ 5.1 and group 4: DAS28 > 5.1. Rheumatoid factor (RF) was measured by latex agglutination test, and anti-cyclic citrullinated peptide (anti-CCP) antibodies were detected by ELISA with a commercial kit. Fifty-seven female RA patients (mean age: 46.02 ± 13.47 years, mean disease duration: 115.77 ± 99.44 months) and sixty gender- and age-paired healthy controls were included. Mean MPO plasma levels were significantly higher in patients than in controls (72.27 pM vs. 40.78 pM, P = 0.007). RF was found in 59.6% and anti-CCP in 80.7% of the RA patients. No significant difference in MPO levels was seen among the four RA disease activity groups. We did not find significant correlation between MPO levels and disease activity as measured by DAS28 score. In conclusion, we observed significantly higher MPO plasma levels in RA patients when compared to healthy controls. However, we did not find correlation between MPO plasma level and disease activity.

Increased plasma myeloperoxidase levels in systemic lupus erythematosus.

The objective of the study was to quantify plasma myeloperoxidase (MPO) levels in systemic lupus erythematosus (SLE) patients and to evaluate a correlation between MPO levels and disease activity. 71 female SLE patients and 70 controls were studied. Patients were divided into two groups: Group I (n = 48) with SLEDAI-2K score 0-5 and Group II (n = 23) with SLEDAI-2K score > or = 6. Mann-Whitney test and Spearman rank correlation were used. Two-sided P values < 0.05 were considered significant and P values > or = 0.05 and < 0.08 were considered as a tendency. The median age of patients and controls were comparable and the mean disease duration was 99.2 +/- 61.7 months. MPO levels were higher in patients than controls [5.99 (4.38-8.64) vs. 5.00 (3.33-7.08) ng/ml, P = 0.02]. We did not find correlation between MPO levels and SLEDAI-2k (r = 0.07, P = 0.58). MPO levels were not affected by treatment with prednisone, cyclophosphamide or azathioprine, however, a tendency of lower levels was observed among patients under antimalarial drugs. There was no significant difference in MPO plasma levels between Group I and Group II (5.83 vs. 6.02 ng/ml, P = 0.99). MPO levels were higher in patients with arthritis than in those without arthritis (8.15 vs. 5.56 ng/ml, P = 0.010). No difference was observed among patients with and without other organs/systems involvement. SLE patients presented increased MPO plasma levels than healthy controls. Despite the lack of correlation between MPO plasma levels and disease activity, the higher MPO levels in patients with articular involvement suggests MPO may play a different role in the inflammatory process of some SLE manifestations.

Redefining the Scl-70 indirect immunofluorescence pattern: autoantibodies to DNA topoisomerase I yield a specific compound immunofluorescence pattern.

OBJECTIVES: To report on a novel IIF pattern specifically associated with antibodies to DNA topo I. METHODS: A novel compound IF pattern, designated Scl-70 pattern, was characterized in routine ANA-HEp-2 IIF screening. Within the last 3 years, all serum samples presenting the Scl-70 pattern at the ANA-HEp2 IIF screening were tested for anti-topo I reactivity. Conversely, 16 serum samples with known anti-topo I reactivity and affinity-purified anti-topo I antibody preparations were tested for the Scl-70 pattern. RESULTS: The Scl-70 pattern comprised the staining of five cellular regions: nucleus, nucleolus and cytoplasm in interphase cells; nucleolar organizing region (NOR) and chromosomes in mitotic cells. All 81 serum samples selected as Scl-70 pattern reacted with topo I. All 16 anti-topo I samples and antibody preparations reproduced the Scl-70 pattern. This compound IF pattern was consistently observed in different commercial HEp-2 cell slides and in home-made slides with HEp-2 cells and human fibroblasts fixed with alternative protocols. Double IIF experiments demonstrated the co-localization of topo I and human upstream binding factor at the NOR. CONCLUSIONS: The Scl-70 pattern belongs to the group of compound IF patterns that hold strong association with the respective autoantibody specificities, such as that observed with centromere protein F (CENP-F) and nuclear mitotic apparatus-1 (NuMA-1) protein. The identification of the Scl-70 pattern at routine ANA-HEp-2 IIF screening may lead to implementation of specific tests for the identification of anti-topo I antibodies. In addition, the Scl-70 pattern outlines cellular domains other than those previously reported for topo I, which is of interest for further understanding the roles of this enzyme in cell biology.

Impact of C4, C4A and C4B gene copy number variation in the susceptibility, phenotype and progression of systemic lupus erythematosus.

BACKGROUND: Complement component 4 (C4) gene copy number (GCN) affects the susceptibility to systemic lupus erythematosus (SLE) in different populations, however the possible phenotype significance remains to be determined. This study aimed to associate C4A, C4B and total C4 GCN and SLE, focusing on the clinical phenotype and disease progression. METHODS: C4, C4A and C4B GCN were determined by real-time PCR in 427 SLE patients and 301 healthy controls, which underwent a detailed clinical evaluation according to a pre-established protocol. RESULTS: The risk of developing SLE was 2.62 times higher in subjects with low total C4 GCN (< 4 copies, OR = 2.62, CI = 1.77 to 3.87, p < 0.001) and 3.59 times higher in subjects with low C4A GCN (< 2 copies; OR = 3.59, CI = 2.15 to 5.99, p < 0.001) compared to those subjects with normal or high GCN of total C4 (≥4) and C4A (≥2), respectively. An increased risk was also observed regarding low C4B GCN, albeit to a lesser degree (OR = 1.46, CI = 1.03 to 2.08, p = 0.03). Furthermore, subjects with low C4A GCN had higher permanent disease damage as assessed by the Systemic Lupus International Collaborating Clinics - Damage Index (SLICC-DI; median = 1.5, 95% CI = 1.2-1.9) than patients with normal or high copy number of C4A (median = 1.0, 95% CI = 0.8-1.1; p = 0.004). There was a negative association between low C4A GCN and serositis (p = 0.02) as well as between low C4B GCN and arthritis (p = 0.02). CONCLUSIONS: This study confirms the association between low C4 GCN and SLE susceptibility, and originally demonstrates an association between low C4A GCN and disease severity.

Primary immunodeficiency association with systemic lupus erythematosus: review of literature and lessons learned by the Rheumatology Division of a tertiary university hospital at São Paulo, Brazil.

Primary immunodeficiency disorders (PID) represent a heterogeneous group of diseases resulting from inherited defects in the development, maturation and normal function of immune cells; thus, turning individuals susceptible to recurrent infections, allergy, autoimmunity, and malignancies. In this retrospective study, autoimmune diseases (AIDs), in special systemic lupus erythematosus (SLE) which arose associated to the course of PID, are described. Classically, the literature describes three groups of PID associated with SLE: (1) deficiency of Complement pathway components, (2) defects in immunoglobulin synthesis, and (3) chronic granulomatous disease (CGD). Currently, other PID have been described with clinical manifestation of SLE, such as Wiskott-Aldrich syndrome (WAS), autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), autoimmune lymphoproliferative syndrome (ALPS) and idiopathic CD4(+) lymphocytopenia. Also we present findings from an adult cohort from the outpatient clinic of the Rheumatology Division of Universidade Federal de São Paulo. The PID manifestations found by our study group were considered mild in terms of severity of infections and mortality in early life. Thus, it is possible that some immunodeficiency states are compatible with survival regarding infectious susceptibility; however these states might represent a strong predisposing factor for the development of immune disorders like those observed in SLE.

Antinucleosome antibodies and primary antiphospholipid syndrome: an observational study.

OBJECTIVE: To study the association of anti-nucleosome (anti-NCS) antibodies in primary antiphospholipid syndrome (APS) and the development of systemic lupus erythematosus (SLE) during follow-up. MATERIALS AND METHODS: Thirty-six women with primary APS were evaluated prospectively for clinical features of systemic autoimmune diseases and for the presence of antiphospholipid antibodies, antinuclear antibodies and anti-NCS/chromatin antibodies. RESULTS: After a mean follow-up period of 45.7 months, anti-NCS/chromatin antibodies were detected in only one patient (2.8%), who developed features of SLE including polyarthritis, lymphopenia, optic neuritis, multiple sclerosis-like lesions, and an autoantibody profile suggestive of SLE. CONCLUSION: The frequency of anti-NCS/chromatin antibodies in primary APS patients is very low, and they may be associated with the development of SLE manifestations.

Diagnostic performance and clinical associations of antibodies to the chromatin antigenic system in juvenile systemic lupus erythematosus.

OBJECTIVES: To determine the frequency of antibodies to chromatin components in juvenile systemic lupus erythematosus (JSLE), and to correlate the presence of these autoantibodies with clinical manifestations and disease activity. METHODS: Anti-chromatin (anti-CHR), anti-nucleosome core particle (anti-NCS) and anti-dsDNA antibodies were measured in 175 individuals, including 37 patients with active JSLE and 41 with inactive disease, 47 non-lupus autoimmune disease patients (non-lupus AD), and 50 healthy children. An in-house ELISA was developed with purified nucleosome core particles from calf thymus to determine IgG and IgG3 anti-NCS antibodies. Anti-CHR and anti-dsDNA antibodies were detected by commercial ELISA kits (INOVA). RESULTS: Anti-NCS and anti-CHR antibodies exhibited high specificity for JSLE and similar frequency in active and inactive JSLE. Anti-CHR and IgG/IgG3 anti-NCS serum levels did not differ between active and inactive JSLE. SLEDAI correlated with anti-dsDNA antibodies but not with antibodies to other chromatin components. There was association of anti-dsDNA, anti-CHR and IgG/IgG3 anti-NCS antibodies with proteinuria and low C4 serum levels. Anti-NCS antibodies in the absence of anti-dsDNA were observed in 14% of the JSLE patients. CONCLUSIONS: Our data indicate that anti-NCS and anti-CHR antibodies are relevant diagnostic markers for JSLE and appear to be correlated with JSLE lupus nephritis activity. IgG3 isotype anti-NCS antibodies do not seem to be more relevant than IgG anti-NCS antibodies as markers of disease activity or active nephritis in JSLE.

Immune system: part III. The delicate balance of the immune system between tolerance and autoimmunity.

The immune system consists of an intricate network of organs, cells, and molecules responsible for maintaining the body's homeostasis and responding to aggression in general. Innate immunity operates in conjunction with adaptive immunity and is characterized by rapid response to aggression, regardless of previous stimulus, being the organism first line of defense. Its mechanisms include physical, chemical and biological barriers, cellular components, as well as soluble molecules. The organism first line of defense against tissue damage involves several steps closely integrated and constituted by different components of this system. The aim of this review is to restore the foundations of this response, which has high complexity and consists of several components that converge to articulate the development of adaptive immune response. We selected some of the following steps to review: perception and molecular recognition of aggressive agents; activation of intracellular pathways, which result in vascular and tissue changes; production of a myriad of mediators with local and systemic effects on cell activation and proliferation, synthesis of new products involved in the chemoattraction and migration of cells specialized in destruction and removal of offending agent; and finally, tissue recovery with restoration of functional tissue or organ.

Immune system - part I. Fundamentals of innate immunity with emphasis on molecular and cellular mechanisms of inflammatory response.

The immune system consists of an intricate network of organs, cells, and molecules responsible for maintaining the body's homeostasis and responding to aggression in general. Innate immunity operates in conjunction with adaptive immunity and is characterized by rapid response to aggression, regardless of previous stimulus, being the organism first line of defense. Its mechanisms include physical, chemical and biological barriers, cellular components, as well as soluble molecules. The organism first line of defense against tissue damage involves several steps closely integrated and constituted by different components of this system. The aim of this review is to restore the foundations of this response, which has high complexity and consists of several components that converge to articulate the development of adaptive immune response. We selected some of the following steps to review: perception and molecular recognition of aggressive agents; activation of intracellular pathways, which result in vascular and tissue changes; production of a myriad of mediators with local and systemic effects on cell activation and proliferation, synthesis of new products involved in the chemoattraction and migration of cells specialized in destruction and removal of offending agent; and finally, tissue recovery with restoration of functional tissue or organ.

Risk factors for cardiovascular disease and endothelin-1 levels in Takayasu arteritis patients.

The objective of this study was to evaluate traditional risk factors for cardiovascular disease (CVD) and endothelin-1 (ET-1) levels in Takayasu arteritis (TA) patients. Twenty-two TA patients and 37 controls were evaluated. TA patients had a higher prevalence of hypertension (63.6% vs. 21.6%, p=0.001) and higher levels of triglycerides (129.5 mg/dL+/-70.8 vs. 88.4 mg/dL+/-60.8, p=0.017) than controls. Mean number of CVD risk factors was 1.64+/-1.22 in TA patients and 1.03+/-1.44 among controls, p=0.030. More TA patients presented at least one CVD risk factor when compared to controls (77.2% vs. 51.3%, p=0.048). ET-1 levels were higher in patients than in controls (1.49 pg/mL+/-0.45 vs. 1.27 pg/mL+/-0.32, p=0.034), however no significant difference was found between patients with active and inactive disease. In this study, TA patients presented a higher prevalence of hypertension, higher levels of triglycerides, and ET-1 than controls.