[Variables associated with mortality in 103 patients with anti-neutrophil cytoplasmic antibodies associated vasculitis]. / Comportamiento clínico y factores asociados a mortalidad temprana en una cohorte de pacientes chilenos con vasculitis asociadas a anticuerpos anti citoplasma de neutrófilos (VAA).

BACKGROUND: Cumulative survival in patients with anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis (VAA) is 88 and 78% at 1 and 5 years, respectively. Despite this, mortality continues to be 2.7 times higher than the general population. Differences in the clinical profile of VAA in different ethnicities have been observed. AIM: To identify factors at the time of diagnosis, associated with mortality at one year of follow-up and to describe the clinical characteristics of these patients. MATERIAL AND METHODS: We identified in local databases and reviewed clinical records of patients with VAA with at least one year of follow up in a clinical hospital. Demographic and laboratory parameters and clinical activity scores were analyzed. RESULTS: Of 103 patients with VAA identified, 65 met the inclusion criteria and were analyzed. Their age ranged from 45 to 63 years and 56% were women. Thirty-five patients (54%) were diagnosed as granulomatosis with Polyangiitis (GPA) and 30 patients (46%) with Microscopic Polyangiitis (MPA). The frequency of renal disease was 53% and pulmonary involvement occurred in 72%. At one year of follow-up 11 patients died resulting in a mortality of 17%. Seven patients died within three months after diagnosis. MPO ANCA were more common than PR3 ANCA. In the multivariate analysis, the presence of ophthalmological involvement, lung kidney syndrome and a Five Factor Score (FFS) of 1 or more were independent factors associated with mortality at one year. CONCLUSIONS: In these patients, pulmonary manifestations predominate. Lung kidney syndrome, ophthalmological involvement and a FFS score ≥ 1 were associated with mortality.

Septic serum induces glucocorticoid resistance and modifies the expression of glucocorticoid isoforms receptors: a prospective cohort study and in vitro experimental assay.

BACKGROUND: A protective role for glucocorticoid therapy in animal models of sepsis was shown many decades ago. In human sepsis, there is new interest in glucocorticoid therapy at a physiological dose after reports of improved response to vasopressor drugs and decreased mortality in a selected group of patients. However, other reports have not confirmed these results. Cellular glucocorticoid resistance could explain a possible cause of that. To evaluate this hypothesis, we evaluated the expression of glucocorticoid receptor beta, the dominant negative isoform of glucocorticoid receptor, in peripheral mononuclear cells of septic patients and the effect of serum septic patients over glucocorticoid receptor expression and glucocorticoid sensitivity in immune cells culture. METHODS: A prospective cohort study and an in vitro experimental study with matched controls were developed. Nine patients with septic shock and nine healthy controls were prospectively enrolled. Mononuclear cells and serum samples were obtained from the patients with sepsis on admission to the Intensive Care Unit and on the day of discharge from hospital, and from healthy volunteers matched by age and sex with the patients. Glucocorticoid receptor alpha and beta expression from patients and from immune cell lines cultured in the presence of serum from septic patients were studied by western blot. Glucocorticoid sensitivity was studied in control mononuclear cells cultured in the presence of serum from normal or septic patients. A statistical analysis was performed using a Mann-Whitney test for non-parametric data and analysis of variance for multiple comparison; P<0.05 was considered significant. RESULTS: The patients' glucocorticoid receptor beta expression was significantly higher on admission than on discharge, whereas the alpha receptor was not significantly different. In vitro, septic serum induced increased expression of both receptors in T and B cells in culture, with a greater effect on receptor beta than the control serum. Septic serum induced glucocorticoid resistance in control mononuclear cells. CONCLUSION: There is a transient increased expression of glucocorticoid receptor beta in mononuclear cells from septic patients. Serum from septic patients induces cell glucocorticoid resistance in vitro. Our findings support a possible cell glucocorticoid resistance in sepsis.

Effects of methotrexate on the expression of the translational isoforms of glucocorticoid receptors α and ß: correlation with methotrexate efficacy in rheumatoid arthritis patients.

OBJECTIVES: To test the effect of MTX on the expression of glucocorticoid receptor (GR) α and ß isoforms AB, C and D in peripheral blood mononuclear cells (PBMCs) in culture, from newly diagnosed RA patients and to evaluate whether the test results correlate with patients' subsequent response to MTX treatment. METHODS: Twenty patients with early active RA were enrolled. Patients who had previously received any DMARD or cytotoxic agent, or who had received CSs in the 6 months before enrolment were excluded. PBMCs from all patients were obtained and cultured in the presence and absence of MTX (10(-4), 10(-6) and 10(-8) M). The expression of GR isoforms was evaluated by western blot. After blood samples were taken, patients entered a 24-week study receiving MTX, diclofenac and prednisone (10 mg/day). At Week 24, the ACR core set of disease activity measures was calculated and a correlation between the MTX effect on patients' PBMC GR expression in vitro and the ACR response was evaluated. RESULTS: MTX 10(-6) M in the culture medium induced the expression of the PBMC isoform AB of GRα (P = 0.009). Other GR isoforms were unaffected. The magnitude of the induced expression correlated with the ACR response to treatment at Week 24 of therapy (r = 0.92, P = 0.00003). CONCLUSION: MTX in vitro induces greater expression of GRαAB isoform in PBMC from RA patients who later respond to MTX treatment than in non-responding patients. This may have clinical applications for predicting MTX efficacy in RA patients.

Motion correction and myocardial perfusion SPECT using manufacturer provided software. Does it affect image interpretation?

PURPOSE: Myocardial perfusion SPECT is an excellent tool for the assessment of coronary artery disease (CAD); however, it is affected by several artifacts, such as patient motion during acquisition, which increases false-positive rates. Therefore, the purpose of this work is to analyze changes in perfusion scores after motion-correction software application. METHODS: The population included 160 (99m)Tc-sestamibi CAD studies, divided into two groups: with and without perfusion defects, equally divided into subgroups according to movement during standard acquisition. A Siemens ECAM 180 was used for processing without correction and with automatic and manual e.soft 2.5 modalities. Visual interpretation as well as QPS software was compared using Pearson correlation and kappa agreement statistics. RESULTS: Moderate agreement was observed between SPECT interpretations after motion correction versus the original report, according to the presence of perfusion defects. Manual correction using the software obtained the lowest agreements. Perfusion summed stress scores (SSS) correlation from different processing modalities versus non-corrected studies differed significantly independent of the degree of motion. Mean SSS in 40 patients with no motion was 3.9 + or - 3.9 when no correction was applied; with automatic correction was 8.8 + or - 10 (p = 0.03) and with manual correction was 3.1 + or - 3.5 (p = ns versus non-corrected). Automatic correction was better when applied to patients with mild to moderate motion. In those with mild or no motion, software overestimated or created new perfusion defects. CONCLUSION: Motion-correction software must be used with caution when trying to optimize myocardial perfusion SPECT based on individual analysis. Acquisition should be always repeated in cases with severe motion and in no or mild motion it seems preferable to avoid correction.

Interstitial lung disease and microscopic polyangiitis in chilean patients.

OBJECTIVE: To describe the clinical and serological patients characteristics with Microscopic Polyangiitis (MPA) and Interstitial lung disease (ILD). METHODS: Of all the patients with AAV diagnosed between 2007-2017 at the Hospital Clinico Universidad de Chile, those with MPA and ILD were selected and studied retrospectively. RESULTS: All patients were Hispanic; median age at diagnosis 65 years (32-84). 59% were female. All were positive for p-ANCA, 16 patients for MPO. Most common manifestations were constitutional symptoms, weight loss and fever. CT-Scans patterns were Usual Interstitial Pneumonia (UIP) in 10 patients, Nonspecific Interstitial Pneumonia (NSIP) in 6 and fibrosis not UIP or NSIP pattern in 1. In 6 cases, ILD was diagnosed 0.5-14 years before MPA and concomitantly in 11. CONCLUSIONS: Although infrequent, Microscopic Polyangiitis should be suspected in patients with ILD particularly if extra-pulmonary manifestations that rise the possibility of a systemic illness are present, regardless of the time elapsed between the latter and the diagnosis of this type of lung involvement. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (1): 37-42).

Methotrexate regulates the expression of glucocorticoid receptor alpha and beta isoforms in normal human peripheral mononuclear cells and human lymphocyte cell lines in vitro.

MTX is an effective therapy for autoimmune-inflammatory diseases. The mechanisms that mediate these actions are not completely clear. It is accepted that many of these effects are mediated through the release of adenosine with the activation of the adenosine receptor A2. MTX is used as a steroid sparing agent. An improved in vitro GC cell sensitivity in GC insensitive asthma patients has been demonstrated after MTX treatment. Most GC actions are mediated by the GCR. The effect of MTX on GCRs expression has not been previously evaluated. Therefore, we evaluate if MTX regulates the expression of glucocorticoid receptors, increasing the expression of the active receptor (GCR alpha) and/or decreasing the expression of the dominant negative receptor (GCR beta). We show that MTX increases the mRNA and protein levels of GCR alpha and decreases or leaves unchanged the protein expression of the GCR beta in CEM cells in culture. This effect was also observed in other lymphocytes (Jurkat and Raji) and in PBMNC from healthy volunteers. We also show that upon MTX treatment PBMC from normal volunteers exhibit a higher sensitivity to DEX inhibition on LPS-induced TNF alpha release. To explore if these actions are mediated by adenosine through the adenosine receptor A2 we evaluate the effect of adenosine on the GCRs expression and the effect of an A2 receptor blocker (DMPX) on MTX effects on GCRs expression. Our results show that adenosine does not mimic and DMPX can enhance MTX effects on these receptors. We conclude that MTX increases the GCR alpha/GCR beta ratio of expression in lymphocytes which could mediate its previously reported effects in improving cell glucocorticoid sensitivity. These actions are not mediated by the adenosine receptor A2.

Evaluation of the Glucocorticoid Receptor as a Biomarker of Treatment Response in Vogt-Koyanagi-Harada Disease.

Purpose: This study is aimed to investigate the role of glucocorticoid receptor (GR) isoforms in peripheral blood mononuclear cells (PBMC) as biomarkers of glucocorticoid (GC) resistance and to validate a set of clinical predictive factors in patients with Vogt-Koyanagi-Harada (VKH) disease. Methods: This was a prospective cohort study that included a total of 21 patients with VKH. A complete ophthalmologic evaluation was carried out at baseline that recorded the presence of any clinical predictive factors (visual acuity ≤ 20/200, tinnitus, chronic disease, and fundus depigmentation). Real-time quantitative PCR was performed to measure the mRNA levels of GR alpha (GRα) and beta (GRß) isoforms at baseline and at 2 weeks after prednisone therapy initiation. Results: There were no differences between GRα and GRß levels in GC-sensitive and GC-resistant patients at baseline before treatment initiation. After 2 weeks of prednisone treatment, GC-sensitive patients had a median 5.5-fold increase in levels of GRα, whereas GC-resistant patients had a median 0.7-fold decrease in levels of this isoform (P = 0.003). Similarly, GRß increased in GC-sensitive patients, in comparison with GR-resistant patients (6.49-fold versus 1.01 fold, respectively, I = 0.04). The mRNA levels of GR isoforms were independent of disease activity. Fundus depigmentation and chronic disease at diagnosis were associated with GC resistance (P = 0.03, odds ratio = 21.0; and P = 0.008, odds ratio = 37.8, respectively). However, associations with visual acuity or tinnitus were not confirmed in this study. Conclusions: The evaluation of clinical predictive factors and determination of the change in expression of GR isoforms as potential biomarkers can contribute to the early identification of GC-resistant patients with VKH.

LPS regulates the expression of glucocorticoid receptor α and ß isoforms and induces a selective glucocorticoid resistance in vitro.

BACKGROUND: This study was aimed to evaluate the effect of LPS in glucocorticoid receptor (GR) isoforms expression on different cell lines and PBMC from healthy donors in vitro and glucocorticoid sensitivity of PBMC in vitro. METHODS: U-2 OS cell lines expressing GR isoforms, different cell lines (CEM, RAJI, K562 and HeLa) or PBMC from healthy donors, were cultured or not with LPS. The expression of GRα and GRß was evaluated by Western blot. Glucocorticoid sensitivity was evaluated in PBMC treated with LPS, testing genes which are transactivated or transrepressed by glucocorticoid. For transactivated genes (MKP1, FKBP5) PBMC were treated with Dexamethasone 100 nM for 6 h. The mRNA expression was measured by RT-PCR. For transrepressed genes (IL-8, GM-CSF), PBMC were cultured in Dexamethasone 100 nM and LPS 10 µg/ml for 6 h and protein expression was measure by ELISA. RESULTS: GR isoforms were induced in U-2 OS cells with a greater effect on GRα expression. Both isoforms were also induced in CEM cells with a tendency to a greater effect on GRß. LPS induced only the expression of GRα in Raji and HeLa cells, and in PBMC, with no effect in K562 cells. LPS induced a loss of glucocorticoid inhibitory effect only on the secretion of GM-CSF. CONCLUSION: LPS in vitro differentially modulates the expression of GR isoforms in a cell specific manner. In PBMC from healthy donors LPS induces an approximately two times increase in the expression of GRα and a loss of the glucocorticoid inhibitory effect on the secretion of GM-CSF, without affecting other glucocorticoid responses evaluated.

Comportamiento clínico y factores asociados a mortalidad temprana en una cohorte de pacientes chilenos con vasculitis asociadas a anticuerpos anti citoplasma de neutrófilos (VAA) / Variables associated with mortality in 103 patients with anti-neutrophil cytoplasmic antibodies associated vasculitis

Background: Cumulative survival in patients with anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis (VAA) is 88 and 78% at 1 and 5 years, respectively. Despite this, mortality continues to be 2.7 times higher than the general population. Differences in the clinical profile of VAA in different ethnicities have been observed. Aim: To identify factors at the time of diagnosis, associated with mortality at one year of follow-up and to describe the clinical characteristics of these patients. Material and Methods: We identified in local databases and reviewed clinical records of patients with VAA with at least one year of follow up in a clinical hospital. Demographic and laboratory parameters and clinical activity scores were analyzed. Results: Of 103 patients with VAA identified, 65 met the inclusion criteria and were analyzed. Their age ranged from 45 to 63 years and 56% were women. Thirty-five patients (54%) were diagnosed as granulomatosis with Polyangiitis (GPA) and 30 patients (46%) with Microscopic Polyangiitis (MPA). The frequency of renal disease was 53% and pulmonary involvement occurred in 72%. At one year of follow-up 11 patients died resulting in a mortality of 17%. Seven patients died within three months after diagnosis. MPO ANCA were more common than PR3 ANCA. In the multivariate analysis, the presence of ophthalmological involvement, lung kidney syndrome and a Five Factor Score (FFS) of 1 or more were independent factors associated with mortality at one year. Conclusions: In these patients, pulmonary manifestations predominate. Lung kidney syndrome, ophthalmological involvement and a FFS score ≥ 1 were associated with mortality.

Earlier immunomodulatory treatment is associated with better visual outcomes in a subset of patients with Vogt-Koyanagi-Harada disease.

PURPOSE: To evaluate clinical outcomes of first-line immunomodulatory therapy (IMT) and prednisone alone or late IMT in Vogt-Koyanagi-Harada disease. METHODS: Retrospective cohort study of 152 patients with Vogt-Koyanagi-Harada disease evaluated in a referral uveitis clinic in Chile from 1985 to 2011. Medical records of these patients were reviewed. Demographic data, clinical evaluation, type of treatment, functional outcomes, glucocorticoid (GC) dose and complications were recorded. Multivariate logistic regression was used to identify prognostic factors of poor response to GC. RESULTS: There were no significant differences between first-line IMT group and prednisone alone/late IMT group in terms of visual acuity (VA) improvement, complications and GC sparing effect. There was a trend for a higher frequency of systemic adverse effects leading to discontinuation of treatment in patients receiving IMT than in those receiving prednisone (14.6% and 6.5%, respectively). The subgroup of patients with poor response to GC who showed functional improvement had a significantly earlier time to IMT initiation than the patients who had no improvement. We identified following prognostic factors of poor response to GC: VA ≤ 20/200, fundus depigmentation, chronic disease and tinnitus at diagnosis. Patients with a prognostic factor (excluding tinnitus) and VA improvement had an earlier IMT initiation than those who had worse functional outcome. CONCLUSION: There were no differences in outcomes between first-line IMT and prednisone alone/late IMT in the entire VKH group. However, in a subset of patients, there was a significant better functional outcome with earlier IMT initiation.

The presence of anti-citrullinated protein antibodies (ACPA) does not affect the clinical response to adalimumab in a group of RA patients with the tumor necrosis factor (TNF) α-308 G/G promoter polymorphism.

The introduction of antitumor necrosis factor (TNF) agents has improved the outcome for many patients with rheumatoid arthritis (RA). To date, the only replicated genetic predictor of anti-TNF response is the -308 G > A single-nucleotide polymorphism in the TNF promoter region. The presence of the -308 TNF G/G genotype appears to be a marker of good response to anti-TNF treatment. Anti-citrullinated protein antibodies (ACPA) have been linked with erosive disease, and have been established as the single most reliable prognostic factor in clinical practice. To test the hypothesis that the ACPA status may affect the -308 G/G patients rate of response to TNF blockade, we prospectively investigated a group of 52 RA patients with the -308 G/G genotype who were ACPA (+) or ACPA (-). All patients were treated with adalimumab, and the clinical response was studied using the Disease Activity Score in 28 joints (DAS28) at 24 weeks of treatment. Over 85% of patients were DAS28 responders in both groups. No significant differences were found between patients from both groups, according to the DAS28 criteria of response at week 24 (p = 0.79). In conclusion, our findings suggest that the ACPA status does not affect the clinical response to anti-TNF therapy in -308 TNF G/G patients.

L-type calcium channels in growth plate chondrocytes participate in endochondral ossification.

Longitudinal bone growth occurs by a process called endochondral ossification that includes chondrocyte proliferation, differentiation, and apoptosis. Recent studies have suggested a regulatory role for intracellular Ca(2+) (Ca(i) (2+)) in this process. Indirect studies, using Ca(2+) channel blockers and measurement of Ca(i) (2+), have provided evidence for the existence of Ca(2+) channels in growth plate chondrocytes. Furthermore, voltage-gated Ca(2+) channels (VGCC), and specifically L- and T-type VGCCs, have been recently described in murine embryonic growth plates. Our aim was to assess the effect of L-type Ca(2+) channel blockers on endochondral ossification in an organ culture. We used cultures of fetal rat metatarsal rudiments at 20 days post gestational age, with the addition of the L-type Ca(2+) channel blockers verapamil (10-100 microM) or diltiazem (10-200 microM) to the culture medium. Longitudinal bone growth, chondrocyte differentiation (number of hypertrophic chondrocytes), and cell proliferation (incorporation of tritiated thymidine) were measured. Verapamil dose-dependently decreased growth, the number of hypertrophic chondrocytes, and cell proliferation, at concentrations of 10-100 microM. Growth and the number of hypertrophic chondrocytes decreased significantly with diltiazem at 50-100 microM, and proliferation decreased significantly at concentrations of 10-200 microM. Additionally, there was no increase in apoptosis over physiological levels with either drug. We confirmed the presence of L-type VGCCs in rat rudiments using immunohistochemistry, and showed that the antagonists did not alter the pattern of VGCC expression. In conclusion, our data suggest that L-type Ca(2+) channel activity in growth plate chondrocytes is necessary for normal longitudinal growth, participating in chondrocyte proliferation and differentiation.

Comparison of radionuclide ventriculography using SPECT and planar techniques in different cardiac conditions.

PURPOSE: Accurate assessment of ventricular function is required to optimize therapeutic management of cardiac diseases. The aim of this study was to correlate planar equilibrium multigated acquisition (MUGA) with tomographic ventriculography (SPECT) in patients with diverse volumes and wall motion abnormalities. METHODS: Eighty-three studies in 80 patients (56+/-14 years; 56% women) were classified according to ventricular dilation, wall motion abnormalities and systolic dysfunction. Left and right ventricular ejection fraction (LVEF and RVEF) and end-diastolic and end-systolic left ventricular volumes (EDV and ESV) were obtained using a commercial QBS program for SPECT. On planar acquisition, LVEF and RVEF were obtained using standard techniques and volumes were determined using the count-based method, without blood sampling. RESULTS: A. Total group: With the planar method, LVEF was 44+/-17%, RVEF 42+/-13%, left EDV 147+/-97 ml (range 31-487 ml) and left ESV 93+/-85 ml (range 15-423 ml); with SPECT the corresponding values were 40+/-20%, 49+/-16%,131+/-95 ml and 91+/-89 ml, respectively (p=NS for all but RVEF). Linear correlation was 0.845 for LVEF, 0.688 for RVEF, 0.927 for left EDV and 0.94 for left ESV, with good intra-class correlation. B. Subgroups: Global and intra-class correlations between planar imaging and SPECT were high for volumes, RVEF and LVEF in all subgroups, except in patients with normal wall motion and function, who showed smaller volumes with SPECT. The group with diffuse wall motion abnormalities had a lower EDV on SPECT. In the abnormal left ventricle, RVEF was higher with SPECT. CONCLUSION: Good correlation and agreement exist between SPECT and planar MUGA with respect to LVEF and left ventricular volumes. SPECT is useful in patients with functional abnormalities, but less reliable in those with normal small cavities. A combined technique is still necessary, and RVEF should be interpreted cautiously.

Anti-tumor necrosis factor-alpha therapy augments dipeptidyl peptidase IV activity and decreases autoantibodies to GRP78/BIP and phosphoglucose isomerase in patients with rheumatoid arthritis.

OBJECTIVE: To assess the enzymatic activity and biochemical status of dipeptidyl peptidase IV (DPP IV), an enzyme that participates in the degradation of proinflammatory molecules, in sera from a group of patients with rheumatoid arthritis (RA; n = 15) treated with a human anti-tumor necrosis factor-a (anti-TNF-alpha) antibody (adalimumab) for 32 weeks. IgG antibody titers against chaperone Bip (GRP78), phosphoglucose isomerase (PGI), lactate dehydrogenase (LDH), fibronectin (FN), and actin were also studied. METHODS: DPP IV activity was measured in sera using Gly-Pro-p-nitroanilide as substrate. The biochemical profile of circulating DPP IV glycoforms was assessed by isoelectric focusing gel electrophoresis. All IgG autoantibody titers and their sialylation levels were determined by ELISA. RESULTS: Patients showed significant increases in serum DPP IV enzymatic activity from basal values (3.554 +/- 1.096) with respect to those obtained at 32 weeks (4.787 +/- 0.953; p < 0.05). Changes in the biochemical profile of circulating DPP IV from acidic to more neutral isoelectric point glycoforms were also seen during treatment. The elevated titers of anti-GRP78 and anti-PGI IgG observed at the beginning of treatment decreased significantly during therapy, whereas those of anti-LDH, anti-FN, and anti-actin IgG remained unchanged. At the end of treatment, sialylation levels of anti-GRP78 and anti-PGI IgG antibodies increased to nearly normal levels. The DPP IV biochemical changes were accompanied by a significant improvement of the Disease Activity Score (DAS28). CONCLUSION: The reduced activity of DPP IV along with increased titers of circulating antibodies to GRP78 and PGI may play a role in the pathogenesis of RA and can be successfully modified by administration of adalimumab.

[Intestinal necrosis as clinical presentation of Takayasu arteritis]. / Necrosis intestinal como presentación de enfermedad de Takayasu.

A 32 years old female was admitted to hospital due to acute abdominal pain, nausea, vomiting and liquid stools. Physical examination was normal except for pain on her left inferior abdominal quadrant without peritoneal irritation signs. An abdominal CAT-scan suggested thrombosis at celiac trunk, although the echo Doppler showed no alterations except for signs of ischemia in the distal branch of the superior mesenteric artery. An exploratory laparotomy was performed disclosing a necrosis of the distal ileum and cecum, diffuse peritonitis and thrombosis of the ileocecoapendiculocolic artery. No vasculitis lesions were found in the arteries of medium size examined. A history of intermittent claudication for the past 3 years as well as acrocyanosis, asymmetry of pulses and blood pressure in the superior extremities was ascertained after the surgery. A MRI angiogram showed multiple stenoses and irregularities at the celiac trunk, hepatic, superior mesenteric and fibular arteries. No abnormalities at the aortic arch and its main branches were documented. A sepsis due to Candida sp complicated her postoperative period. After recovery, prednisone 1 mg/kg/day was started and the anticoagulation continued. The abdominal pain, intermittent claudication and superior limb acrocyanosis disappeared. This is an unusual case of type IV Takayasu's arteritis with acute abdominal signs as the first manifestation.

[Antibodies against recombinant Ro 60 Kd, Ro 52 and La 48 Kd proteins in primary Sjogren's Syndrome. Utility of analytic methods combination to detect antibodies anti Ro and La]. / Anticuerpos a proteínas recombinantes Ro60 Kd, Ro52 Kd y La48 Kd, en el síndrome de Sjögren primario. Utilidad de la combinación de métodos analíticos para detectar anticuerpos anti Ro y anti La.

BACKGROUND: The use of new recombinant antigens may increase the sensitivity and specificity of the detection of anti Ro and anti La antibodies in Sjögren's syndrome. AIM: To determine the immune reactivity of sera from patients with Sjögren's syndrome, against fusion recombinant proteins (prf) Ro60 Kd, Ro52 Kd and La48 Kd expressed in E coli and recombinant protein Ro52 Kd, expressed in baculovirus (prb). MATERIAL AND METHODS: Serum samples from 46 patients with a diagnosis of Sjögren's syndrome, according to the European criteria of 1997, were studied. Using conventional ELISA assays, 32 patients had positive anti Ro antibodies (group A) and 16 patients had negative anti Ro and anti La antibodies, but had positive antinuclear antibodies or rheumatoid factors (group B). Antibodies against recombinant proteins were measured by ELISA or Western Blot. RESULTS: Reactivity against prf Ro60 was present in 69% of samples from group A patients and in 36% of samples from group B. Reactivity against prf Ro52 was present in 94% of samples from group A and 50% of samples from group B. Reactivity against prb Ro52 was present in 75% of samples from group A and 40% of samples from group B. Reactivity against prf La was present in 78% of samples by ELISA and 97% of samples by Western Blot. In 10 of 14 serum samples from group B patients, there was reactivity against at least one recombinant protein. CONCLUSIONS: A high prevalence of reactivity against recombinant Ro and La proteins was detected in serum samples from patients with Sjögren syndrome.

Streptokinase promotes development of dipeptidyl peptidase IV (CD26) autoantibodies after fibrinolytic therapy in myocardial infarction patients.

Dipeptidyl peptidase IV (DPP IV) (CD26) plays a critical role in the modulation and expression of autoimmune and inflammatory diseases. We recently reported that sera from patients with rheumatoid arthritis and systemic lupus erythematosus contained low levels of DPP IV and high titers of anti-DPP IV autoantibodies of the immunoglobulin A (IgA) and IgG classes and found a correlation between the low circulating levels of DPP IV and the high titers of anti-DPP IV autoantibodies of the IgA class. Since streptokinase (SK) is a potent immunogen and binds to DPP IV, we speculated that patients with autoimmune diseases showed higher DPP IV autoantibody levels than healthy controls as a consequence of an abnormal immune stimulation triggered by SK released during streptococcal infections. We assessed this hypothesis in a group of patients suffering from acute myocardial infarction, without a chronic autoimmune disease, who received SK as part of therapeutic thrombolysis. Concomitant with the appearance of anti-SK antibodies, these patients developed anti-DPP IV autoantibodies. These autoantibodies bind to DPP IV in the region which is also recognized by SK, suggesting that an SK-induced immune response is responsible for the appearance of DPP IV autoantibodies. Furthermore, we determined a correlation between high titers of DPP IV autoantibodies and an augmented clearance of the enzyme from the circulation. Serum levels of the inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) increased significantly after 30 days of SK administration, while the levels of soluble IL-2 receptor remained unchanged during the same period, suggesting a correlation between the lower levels of circulating DPP IV and higher levels of TNF-alpha and IL-6 in serum in these patients.

Arteritis de celulas gigantes: clásicos y novedades que vale la pena recordar / Giant cells arteritis: classics and innovations for remember

La Arteritis de Células Gigantes (ACG) es una vasculitis frecuente que ocurre en personas mayores y que afecta principalmente vasos craneanos. Generalmente se acompaña de síntomas sistémicos, claudicación mandibular y alteraciones visuales. La Polimialgia Reumática (PMR) se caracteriza por dolor y rigidez de cintura escapular y pelviana que presenta síntomas constitucionales y reacciones sistémicas. En los últimos años, ha aparecido evidencia que relaciona ambas entidades como componentes de una misma enfermedad. En este artículo se revisan aspectos nuevos en diagnóstico, terapia y etiopatogenia de la ACG y sus relaciones con PMR.

The Giant cell arteritis (GCA) is a common vasculitic syndrome occurring in older persons and it preferentially affects cranial arteries. Generally accompanied by constitutional symptoms and typical findings like jaw claudication and vision disorder.Polymyalgia Rheumatica (PMR) is caracterized by pain and stiffness involving shoulder and pelvic girdless with constitutional symptoms and findings of a systemic reaction. In recents years, evidence linking both conditions as components of asingle disease process has been accumulated. In the present article, we review new aspects of the diagnosis, therapy and pathogenesis of the GCA, and their relationship.