Factors predictive of serious infections over time in systemic lupus erythematosus patients: data from a multi-ethnic, multi-national, Latin American lupus cohort.

AIM: The aim of this study was to identify factors predictive of serious infections over time in patients with systemic lupus erythematosus (SLE). METHODS: A multi-ethnic, multi-national Latin American SLE cohort was studied. Serious infection was defined as one that required hospitalization, occurred during a hospitalization or led to death. Potential predictors included were sociodemographic factors, clinical manifestations (per organ involved, lymphopenia and leukopenia, independently) and previous infections at baseline. Disease activity (SLEDAI), damage (SLICC/ACR Damage Index), non-serious infections, glucocorticoids, antimalarials (users and non-users), and immunosuppressive drugs use; the last six variables were examined as time-dependent covariates. Cox regression models were used to evaluate the predictors of serious infections using a backward elimination procedure. Univariable and multivariable analyses were performed. RESULTS: Of the 1243 patients included, 1116 (89.8%) were female. The median (interquartile range) age at diagnosis and follow-up time were 27 (20-37) years and 47.8 (17.9-68.6) months, respectively. The incidence rate of serious infections was 3.8 cases per 100 person-years. Antimalarial use (hazard ratio: 0.69; 95% confidence interval (CI): 0.48-0.99; p = 0.0440) was protective, while doses of prednisone >15 and ≤60 mg/day (hazard ratio: 4.18; 95 %CI: 1.69-10.31; p = 0.0019) and >60 mg/day (hazard ratio: 4.71; 95% CI: 1.35-16.49; p = 0.0153), use of methylprednisolone pulses (hazard ratio: 1.53; 95% CI: 1.10-2.13; p = 0.0124), increase in disease activity (hazard ratio: 1.03; 95% CI: 1.01-1.04; p = 0.0016) and damage accrual (hazard ratio: 1.22; 95% CI: 1.11-1.34; p < 0.0001) were predictive factors of serious infections. CONCLUSIONS: Over time, prednisone doses higher than 15 mg/day, use of methylprednisolone pulses, increase in disease activity and damage accrual were predictive of infections, whereas antimalarial use was protective against them in SLE patients.

Predictive factors of flares in systemic lupus erythematosus patients: data from a multiethnic Latin American cohort.

Purpose The purpose of this paper is to determine the factors predictive of flares in systemic lupus erythematosus (SLE) patients. Methods A case-control study nested within the Grupo Latino Americano De Estudio de Lupus (GLADEL) cohort was conducted. Flare was defined as an increase ≥4 points in the SLEDAI. Cases were defined as patients with at least one flare. Controls were selected by matching cases by length of follow-up. Demographic and clinical manifestations were systematically recorded by a common protocol. Glucocorticoid use was recorded as average daily dose of prednisone and antimalarial use as percentage of time on antimalarial and categorized as never (0%), rarely (>0-25%), occasionally (>25%-50%), commonly (˃50%-75%) and frequently (˃75%). Immunosuppressive drugs were recorded as used or not used. The association between demographic, clinical manifestations, therapy and flares was examined using univariable and multivariable conditional logistic regression models. Results A total of 465 cases and controls were included. Mean age at diagnosis among cases and controls was 27.5 vs 29.9 years, p = 0.003; gender and ethnic distributions were comparable among both groups and so was the baseline SLEDAI. Independent factors protective of flares identified by multivariable analysis were older age at diagnosis (OR = 0.929 per every five years, 95% CI 0.869-0.975; p = 0.004) and antimalarial use (frequently vs never, OR = 0.722, 95% CI 0.522-0.998; p = 0.049) whereas azathioprine use (OR = 1.820, 95% CI 1.309-2.531; p < 0.001) and SLEDAI post-baseline were predictive of them (OR = 1.034, 95% CI 1.005-1.064; p = 0.022). Conclusions In this large, longitudinal Latin American cohort, older age at diagnosis and more frequent antimalarial use were protective whereas azathioprine use and higher disease activity were predictive of flares.

Impact of cognitive impairment, depression, disease activity, and disease damage on quality of life in women with systemic lupus erythematosus.

OBJECTIVES: To define the relative role of cognitive impairment, depression, disease activity, and disease damage in the decreased health-related quality of life (HRQoL) frequently observed in systemic lupus erythematosus (SLE) patients. METHOD: We studied 101 Chilean female SLE patients and applied the 12-item Medical Outcomes Study (MOS) Short Form Health Survey version 2 (SF-12v2) to assess HRQoL and the Cambridge Neuropsychological Test Automated Battery (CANTAB) to assess cognitive function. Analysis of covariance (ANCOVA) models included demographic and disease-related factors and cognitive function tests of sustained attention, memory, and executive function. RESULTS: All measures of HRQoL were lower in the 101 female SLE patients compared to the women from the Chilean general population. HRQoL was associated with the following factors: (i) depression symptoms, which were detrimental to all components of the physical and mental HRQoL scores; (ii) executive dysfunction (spatial planning), which was associated with lower scores on role limitations due to physical health problems and emotional problems, and general health perceptions; (iii) higher activity and organ damage were deleterious to role physical, bodily pain, and physical summary scores; and (iv) higher damage also impacted physical function. Impairments in sustained attention and memory did not decrease the HRQoL. CONCLUSIONS: Our results highlight the relevance of executive dysfunction to poor physical and mental health components of HRQoL in SLE together with depression, while disease activity and disease damage are associated with lower HRQoL physical components. The need for cognitive function evaluation and rehabilitation in SLE is indicated.

Lupus in Latin-American patients: lessons from the GLADEL cohort.

The need for comprehensive published epidemiologic and clinical data from Latin American systemic lupus erythematosus (SLE) patients motivated the late Dr Alarcón-Segovia and other Latin American professionals taking care of these patients to spearhead the creation of the G: rupo L: atino A: mericano D: e E: studio del L: upus (GLADEL) cohort in 1997. This inception cohort recruited a total of 1480 multiethnic (Mestizo, African-Latin American (ALA), Caucasian and other) SLE patients diagnosed within two years from the time of enrollment from 34 Latin American centers with expertise in the diagnosis and management of this disease. In addition to the initial 2004 description of the cohort, GLADEL has contributed to improving our knowledge about the course and outcome of lupus in patients from this part of the Americas. The major findings from this cohort are highlighted in this review. They have had important clinical implications for the adequate care of SLE patients both in Latin America and worldwide where these patients may have emigrated.

Anti-N-methyl-D-aspartate receptor and anti-ribosomal-P autoantibodies contribute to cognitive dysfunction in systemic lupus erythematosus.

OBJECTIVE: Autoantibodies against N-methyl-D-aspartate receptor (anti-NMDAR) and ribosomal-P (anti-P) antigens are potential pathogenic factors in the frequently observed diffuse brain dysfunctions in patients with systemic lupus erythematosus (SLE). Although studies have been conducted in this area, the role of anti-NMDAR antibodies in SLE cognitive dysfunction remains elusive. Moreover, the specific contribution of anti-P antibodies has not been reported yet. The present study attempts to clarify the contribution of anti-NMDAR and anti-P antibodies to cognitive dysfunction in SLE. METHODS: The Cambridge Neuropsychological Test Automated Battery (CANTAB) was used to assess a wide range of cognitive function areas in 133 Chilean women with SLE. ANCOVA models included autoantibodies, patient and disease features. RESULTS: Cognitive deficit was found in 20%. Higher SLEDAI-2K scores were associated with impairment in spatial memory and learning abilities, whereas both anti-NMDAR and anti-P antibodies contributed to deficits in attention and spatial planning abilities, which reflect fronto-parietal cortex dysfunctions. CONCLUSIONS: These results reveal an association of active disease together with specific circulating autoantibodies, such as anti-NMDAR and anti-P, with cognitive dysfunction in SLE patients.

Late-onset systemic lupus erythematosus in Latin Americans: a distinct subgroup?

OBJECTIVE: To examine the characteristics of patients who developed late onset systemic lupus erythematosus (SLE) in the GLADEL (Grupo Latino Americano de Estudio del Lupus) cohort of patients with SLE. METHODS: Patients with SLE of less than two years of disease duration, seen at 34 centers of nine Latin American countries, were included. Late-onset was defined as >50 years of age at time of first SLE-related symptom. Clinical and laboratory manifestations, activity index (SLEDAI), and damage index (SLICC/ACR- DI) were ascertained at time of entry and during the course (cumulative incidence). Features were compared between the two patient groups (<50 and ≥50) using descriptive statistics and hypothesis tests. Logistic regression was performed to examine the association of late-onset lupus, adjusting for other variables. RESULTS: Of the 1480 patients included, 102 patients (6.9 %) had late-onset SLE, 87% of which were female. Patients with late-onset SLE had a shorter follow-up (3.6 vs. 4.4 years, p < 0.002) and a longer time to diagnosis (10.1 vs. 5.8 months, p < 0.001) compared to the younger onset group. Malar rash, photosensitivity, and renal involvement were less prevalent while interstitial lung disease, pleural effusions, and sicca symptoms were more frequent in the older age group (p > 0.05). In multivariable analysis, late onset was independently associated with higher odds of ocular (OR = 3.66, 95% CI = 2.15-6.23), pulmonary (OR = 2.04, 95% CI = 1.01-4.11), and cardiovascular (OR = 1.76, 95% CI = 1.04-2.98) involvement and lower odds of cutaneous involvement (OR = 0.41, 95% CI = 0.21-0.80), number of cumulative SLE criteria (OR = 0.79, 95% CI = 0.64-0.97), use of cyclophosphamide (OR = 0.47, 95% CI = 0.24-0.95), and anti-RNP antibodies (OR = 0.43, 95% CI = 0.20-0.91). A Cox regression model revealed a higher risk of dying in older onset than the younger-onset SLE (OR = 2.61, 95% CI = 1.2-5.6). CONCLUSION: Late-onset SLE in Latin Americans had a distinct disease expression compared to the younger-onset group. The disease seems to be mild with lower cumulative SLE criteria, reduced renal/mucocutaneous involvements, and less use of cyclophosphamide. Nevertheless, these patients have a higher risk of death and of ocular, pulmonary, and cardiovascular involvements.

Systemic lupus erythematosus impairs memory cognitive tests not affected by depression.

OBJECTIVE: Our aim was to assess the contribution of depression to cognitive impairment in patients with systemic lupus erythematosus (SLE). METHODS: Clinical features, education, age, and Hospital Anxiety and Depression Scale (HADS) were evaluated in 82 patients with SLE and 22 healthy controls, all Chilean women. The Cambridge Neuropsychological Test Automated Battery (CANTAB eclipseTM) assessing attention, spatial memory, and learning and executive function domains was applied. Cognitive deficit definition: a cut-off for definite impairment was defined as a score below -2 standard deviations in at least one outcome measure in two or more domains. ANCOVA with stepwise selection evaluated influences of health status (SLE or control), age, education, and HADS depression and anxiety scores on cognitive outcomes. To avoid overfitting, a shrinkage method was performed. Also, adjusted p-values for multiple comparisons were obtained. RESULTS: Cognitive deficit affected 16 (20%) patients, and no controls (p=0.039). Median HADS depression score in SLE patients was 6 (range 0-19) and in controls was 0 (0-19), p<0.001). ANCOVA and shrinkage models showed that worse cognitive performance in sustained attention and spatial working memory tests was explained by the presence of SLE but not depression, whereas depression only affected a measure of executive function (I/ED Stages completed). CONCLUSION: Depression has a limited role in cognitive impairment in SLE. Impairments in sustained attention and spatial working memory are distinctly influenced by yet-unknown disease-intrinsic factors.

Mestizos with systemic lupus erythematosus develop renal disease early while antimalarials retard its appearance: data from a Latin American cohort.

OBJECTIVES: The objective of this paper is to assess the predictors of time-to-lupus renal disease in Latin American patients. METHODS: Systemic lupus erythematosus (SLE) patients (n = 1480) from Grupo Latino Americano De Estudio de Lupus (GLADEL's) longitudinal inception cohort were studied. Endpoint was ACR renal criterion development after SLE diagnosis (prevalent cases excluded). Renal disease predictors were examined by univariable and multivariable Cox proportional hazards regression analyses. Antimalarials were considered time dependent in alternative analyses. RESULTS: Of the entire cohort, 265 patients (17.9%) developed renal disease after entering the cohort. Of them, 88 (33.2%) developed persistent proteinuria, 44 (16.6%) cellular casts and 133 (50.2%) both; 233 patients (87.9%) were women; mean (± SD) age at diagnosis was 28.0 (11.9) years; 12.2% were African-Latin Americans, 42.5% Mestizos, and 45.3% Caucasians (p = 0.0016). Mestizo ethnicity (HR 1.61, 95% CI 1.19-2.17), hypertension (HR 3.99, 95% CI 3.02-5.26) and SLEDAI at diagnosis (HR 1.04, 95% CI 1.01-1.06) were associated with a shorter time-to-renal disease occurrence; antimalarial use (HR 0.57, 95% CI 0.43-0.77), older age at onset (HR 0.90, 95% CI 0.85-0.95, for every five years) and photosensitivity (HR 0.74, 95% CI 0.56-0.98) were associated with a longer time. Alternative model results were consistent with the antimalarial protective effect (HR 0.70, 95% CI 0.50-0.99). CONCLUSIONS: Our data strongly support the fact that Mestizo patients are at increased risk of developing renal disease early while antimalarials seem to delay the appearance of this SLE manifestation. These data have important implications for the treatment of these patients regardless of their geographic location.

The impact of rural residency on the expression and outcome of systemic lupus erythematosus: data from a multiethnic Latin American cohort.

OBJECTIVE: The objective of this paper is to examine the role of place of residency in the expression and outcomes of systemic lupus erythematosus (SLE) in a multi-ethnic Latin American cohort. PATIENTS AND METHODS: SLE patients (< two years of diagnosis) from 34 centers constitute this cohort. Residency was dichotomized into rural and urban, cut-off: 10,000 inhabitants. Socio-demographic, clinical/laboratory and mortality rates were compared between them using descriptive tests. The influence of place of residency on disease activity at diagnosis and renal disease was examined by multivariable regression analyses. RESULTS: Of 1426 patients, 122 (8.6%) were rural residents. Their median ages (onset, diagnosis) were 23.5 and 25.5 years; 85 (69.7%) patients were Mestizos, 28 (22.9%) Caucasians and 9 (7.4%) were African-Latin Americans. Rural residents were more frequently younger at diagnosis, Mestizo and uninsured; they also had fewer years of education and lower socioeconomic status, exhibited hypertension and renal disease more frequently, and had higher levels of disease activity at diagnosis; they used methotrexate, cyclophosphamide pulses and hemodialysis more frequently than urban patients. Disease activity over time, renal damage, overall damage and the proportion of deceased patients were comparable in rural and urban patients. In multivariable analyses, rural residency was associated with high levels of disease activity at diagnosis (OR 1.65, 95% CI 1.06-2.57) and renal disease occurrence (OR 1.77, 95% CI 1.00-3.11). CONCLUSIONS: Rural residency associates with Mestizo ethnicity, lower socioeconomic status and renal disease occurrence. It also plays a role in disease activity at diagnosis and kidney involvement but not on the other end-points examined.

Common mental disorders and psychological distress in systemic lupus erythematosus are not associated with disease activity.

Psychiatric diagnosis in patients with systemic lupus erythematosus (SLE) is controversial: variations have been reported in frequency, diagnostic assays, associations with disease activity, autoantibodies, and contributing social factors. Eighty-three consecutive non-selected Chilean patients with SLE were evaluated for: (i) 26 common mental disorders according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), using the Mini-International Neuropsychiatric Interview (MINI-plus); (ii) psychological suffering measured by Hospital Anxiety and Depression Scale (HADS); (iii) ACR 1999 neuropsychiatric (NP)SLE criteria; (iv) SLE disease activity (SLEDAI-2K); (v) cumulative damage (SLICC/ACR); and (vi) anti-ribosomal P antibodies by enzyme-linked immunoassay and immunoblot. Psychiatric diagnoses occurred in 44.6% of patients; the most frequent (21.7%) was major depressive episode (MDE). No association with lupus activity was observed in patients with a DSM-IV diagnosis or MDE or psychological suffering. ACR 1999 NPSLE criteria were present in 42.2% of patients, the majority corresponding to mood (28.9%) or anxiety disorders (15.6%). Suicidal risk was present in 9.6% of patients. Anti-ribosomal P antibodies (13.3%) were not associated with DSM-IV diagnosis. Severe psychiatric disorders in SLE are common and not associated with disease activity.

Autoantibodies against galectin-8: their specificity, association with lymphopenia in systemic lupus erythematosus and detection in rheumatoid arthritis and acute inflammation.

The role of autoantibodies in the pathogenesis of systemic lupus erythematosus (SLE) has not been completely defined. From more than a hundred autoantibodies described in SLE, relatively few have been associated with clinical manifestations. The glycan-binding proteins of the galectin family can modulate the immune system. Anti-galectin autoantibodies thus could have functional and/or pathogenic implications in inflammatory processes and autoimmunity. We previously reported function-blocking autoantibodies against galectin-8 (Gal-8) in SLE. Here we tested these autoantibodies against a series of other human galectins and demonstrated their specificity for Gal-8, being detectable in 23% of 78 SLE patients. Remarkably, they associated with lymphopenia (50% of 18 anti-Gal-8-positive versus 18% of 60 anti-Gal-8-negative cases, Fisher's Exact test two-tailed: P < 0.012). Lymphopenia is a common clinical manifestation in SLE, yet of unknown mechanism. In addition, six of eight patients with both lymphopenia and malar rash had anti-Gal-8 in their sera. Occurrence of these autoantibodies was not confined to SLE as we also found them in sera of patients with rheumatoid arthritis (16%) and septicemia (20%). This study thus establishes occurrence of specific anti-Gal-8 autoantibodies in autoimmune rheumatic diseases and in acute inflammation, with an apparent association to a clinical subset in SLE.

Evaluación del tratamiento con infliximab en enfermos con artritis inflamatoria refractaria a drogas habituales / Effectiveness of infliximab in patients with inflammatory arthritis refractory to conventional treatment

BACKGROUND: Tumor necrosis factor antagonists are useful in the treatment of several chronic inflammatory immune mediated diseases. AIM: To assess the effects of infliximab in 21 patients with inflammatory arthropaties, refractary to conventional treatment. PATIENTS AND METHODS: Eleven patients with rheumatoid arthritis, seven with psoriatic arthritis and three with spondyloarthritis were treated. The mean duration of the diseases was 10 years. Infliximab was administered intravenously in a dose of 3 mg/kg body weight. A median of 6 doses in 8 months was administered. Effectiveness was assessed in 19 patients that received three or more doses. RESULTS: Infliximab was effective in 16 patients (10 with rheumatoid arthritis, four with psoriasis and two with spondyloarthritis) and ineffective in three. In responsive patients, a reduction in the number of inflammed joints and morning stiffness and an improvement in functional capacity was observed. Fifteen of the 16 patients perceived an improvement in their health status. This answer was concordant with concomitant medical evaluation in 15. Patients that maintained the treatment felt very well, well or regular, whereas five of six patients that discontinued the treatment felt ill. Thirteen patients had adverse effects. Treatment was discontinued in two patients due to drug induced lupus, allergy in 2, hypertension in one, high costs in three and lack of response in three. CONCLUSIONS: Infliximab reduced arthritic activity in 16 of 19 patients with severe treatment refractary arthritis.

Enfermedad de Paget en Chile: una serie de 15 pacientes / Paget disease of bone in Chile: report of 15 cases

BACKGROUND: Paget disease of bone (PD) is a localized disorder of bone remodeling, which leads to bone fragility and deformity. In Chile PD is uncommon. AIM: To study clinical and demographic characteristics of patients with PD seen in the Clinical Hospital of the Catholic University. PATIENTS AND METHODS: Patients with typical radiological and clinical features of PD referred to our institution during the last decade were included in this review. RESULTS: We obtained data from 15 patients with PD (ten males, eight Chilean, six European and one Asian), eleven of them were diagnosed during the last 3 years. The mean age at diagnosis was 68.7 +/- 11.1 years old. No one had first degree relatives with PD. Bone pain was the main complaint in 13 patients and elevated total alkaline phosphatases in the other two. The average duration of the symptoms prior to diagnosis was 38.8 months. Eight patients had monostotic lesions; the most commonly involved sites were the pelvis, spine and femur. Radiological evaluation disclosed sclerotic changes in all patients as well as bone deformity and osteoarthritis in eight patients. Total alkaline phosphatases were elevated in 14 cases (mean: 4 times over the upper normal limit). CONCLUSIONS: When compared to series of the Northern hemisphere, PD in Chile is characterized by an older age at diagnosis, a higher frequency of symptomatic presentation, advanced radiological involvement and greater proportion of complications. PD should be suspected in every patient, Chilean or foreigner, with bone pain or elevated alkaline phosphatases.

Antiribosomal P protein antibodies in Chilean SLE patients: no association with renal disease.

The objective of this work was to determine the frequency and clinical associations of anti-ribosomal P protein antibodies (Anti-P) in a cohort of Chilean patients with systemic lupus erythematosus (SLE). Between 1996 and 1998, 141 consecutive patients with SLE were examined prospectively according with a standard protocol. Disease activity was measured by MEX-SLEDAI in 138 patients. Anti-P positivity was determined by double immune diffusion or Western blot and ELISA. Anti-P was found in 21 (15%) patients. In the Anti-P positive patients recent onset SLE (disease duration of 1 year or less) was more frequent (P = 0.018). Anti-P was found in 23% of 83 patients with active SLE vs 4% of the 55 patients with inactive SLE (Yates corrected P = 0.00479). An association with anti-dsDNA antibodies by Farr assay was observed. Anti-P positive patients had a median Farr of 65 IU/ml (1.4-1240) and Anti-P negative of 12 IU/ml (1.4-992; P-value = 0.0084). During the study only two patients had lupus psychosis and they were Anti-P positive. No association was found with liver disease (six patients, two with Anti-P antibodies) or active glomerulonephritis (22 patients four with Anti-P). Our data shows that the presence of Anti-P antibodies supports the clinical diagnosis of lupus psychosis.

The presence of the HLA-DRB1 shared epitope correlates with erosive disease in Chilean patients with rheumatoid arthritis.

OBJECTIVE: To assess the contribution of the HLA-DRB1 shared epitope (SE) to the radiological outcome of rheumatoid arthritis (RA) after 6 yr of follow-up in a reported series of 129 Chilean patients with established disease. METHODS: A prospective study was conducted between 1992 and 1998 using hand radiographs to assess disease outcome in a published series of patients in whom two doses of the SE were present in 20%, one dose was present in 34% and the SE was absent in 46%. At study entry, 29 of the 92 patients with hand radiographs were at Steinbrocker stages I or II (non-erosive), with a median disease duration of 2.8 yr (0.4-17). RESULTS: In 1998, 113 (87%) of the patients were alive. One hundred and eight patients underwent complete clinical evaluation. Their median age was 57 yr (range 30-81) and the median disease duration was 15 yr (6-50). We were able to study 25 of the 29 patients who had non-erosive disease at study entry in 1992. We found that 10 of 11 patients having one or two doses of the SE developed erosive disease compared with three of 14 without the SE (Yates' corrected P=0.0023, relative risk 4.24, 95% confidence interval 1.53-11.77). CONCLUSIONS: These observations support and extend the notion that the presence of the SE in one or two doses can predict the development of erosions even in RA populations in whom the SE is not as prevalent as in Caucasians.

Prevalence and isotype distribution of antiphospholipid antibodies in Chilean patients with systemic lupus erythematosus (SLE).

Previous studies have demonstrated that ethnicity plays a role in the prevalence, isotype distribution, and clinical significance of anticardiolipin (aCL) and anti-beta2 glycoprotein I (abeta2-GPI) antibodies in systemic lupus erythematosus (SLE) patients. Few studies have been done in Latin American populations. Serum samples from 129 Chilean SLE patients were tested for IgG, IgM and IgA aCL and abeta2-GPI by ELISA. Clinical data were reviewed with the focus on clinical manifestations of antiphospholipid syndrome (APS). Positivity for at least one isotype of aCL was found in 30% of patients, while only 10% were positive for at least one isotype of abeta2-GPI. IgG was the most prevalent isotype for aCL (16%), and the isotype distribution was similar (4%) for abeta2-GPI. In general, the presence of aCL was significantly associated with the presence of abeta2-GPI, but a number of samples were positive for only one antibody, some of them associated with clinical manifestations of APS. ACL antibodies at medium-high titers were significantly correlated with thrombosis (P = 0.0007) and fetal loss (P = 0.009); however, the sensitivity of abeta2-GPI for detecting thrombosis and fetal loss was lower than aCL (19 and 17% vs 56 and 50%, respectively), and the specificity slightly higher (91 and 90% vs 84 and 82%). In Chilean SLE patients, aCL and abeta2-GPI antibodies are important in the evaluation of patients with APS. However, the utility of abeta2-GPI antibodies was limited by the low prevalence of these antibodies in comparison with other ethnic groups. Further studies are needed to define the basis of the observed differences among ethnic groups.

Increased expression of c-rel, from the NF-kappaB/Rel family, in T cells from patients with systemic lupus erythematosus.

OBJECTIVE: To explore the role of the NF-kappaB/Rel transcription factor family in autoimmunity, we investigated whether peripheral blood mononuclear cells (PBMC) and T cells from the blood of patients with systemic lupus erythematosus (SLE) exhibit abnormal expression of c-rel, both when recently isolated and/or during in vitro activation. METHODS: Total RNA and protein extracts were prepared from PBMC and T cells isolated by immunoadsorption with magnetic beads. The relative concentrations of c-rel mRNA and of c-Rel protein were determined by semiquantitative assays of competitive reverse transcriptase-polymerase chain reaction and chemiluminescent immunoblots, respectively. Activity of NF-kappaB/Rel was studied by electrophoretic mobility shift assay of nuclear extracts. RESULTS: Significantly increased levels of c-rel mRNA were found (1) in PBMC from SLE patients (n = 48; p<0.0000001), even during inactive disease (n = 11; p<0.001), compared to controls (n = 54), and (2) in T cells isolated from a subgroup of these patients (n = 11; p<0.00002) and controls (n = 12). c-Rel protein was found increased in the cytosol but not in the nucleus of PBMC of patients with SLE (n = 12; p<0.02) compared to controls (n = 12). No evidence of NF-kappaB/Rel nuclear activity was detected. In vitro stimulation of T cells by incubating PBMC with concanavalin A showed that less c-Rel entered the nucleus in lupus cells than healthy cells, correlating with lower interleukin 2 production. However, the same stimulating conditions provoked an increase in c-rel mRNA to higher levels in lupus cells from 2 patients compared with 2 controls. Increased levels of both IkappaB alpha and IkappaB beta could account for c-Rel cytosolic retention. CONCLUSION: Our data suggest that T cells from patients with SLE possess altered regulatory mechanisms of c-rel expression and nuclear import that might potentially determine conditions for developing autoimmunity. Other cells present in the PBMC could also be affected.

[Capacity to predict a recurrence of lupus erythematosus using double-stranded anti-DNA antibodies and Farr technique]. / Capacidad de predecir una recaída de lupus eritematoso generalizado, mediante anticuerpos anti-DNA de hebra doble, por la técnica de Farr.

BACKGROUND: Patients with inactive systemic lupus erythematosus (SLE) and elevated high affinity double-stranded anti-DNA antibodies (anti-dsDNA), measured using Farr technique, would have a risk of relapse that fluctuates between 40 to 80% according to different series. AIM: To study the association between anti-dsDNA levels measured using Farr technique and disease activity and their predictive capacity for relapses. MATERIAL AND METHODS: Anti-dsDNA antibodies were measured according to Farr method in 60 healthy subjects, 69 patients with other connective tissue diseases and in 120 patients with SLE. Farr positive were considered those individuals with anti-dsDNA levels over 10.4 IU/ml. Disease activity, assessed using MEX-SLEDAI score was related with anti-dsDNA levels in 101 patients. Forty seven patients with inactive disease were followed for 17 +/- 14 months. RESULTS: Anti-dsDNA levels were 3 +/- 2.5 IU/ml (range 1-26) in subjects without LED, and 127 +/- 500 IU/ml (range 1-5280) in patients with LED. Sixty subjects had an active SLE and 43 (72%) were Farr positive; in 41 the disease was inactive and 13 (32%) were Farr positive (p < 0.001), OR 5.45. Twelve of the 47 followed patients had a relapse and 10 (83%) were Farr positive. Of those that did not have a relapse, 13 (37%) were Farr positive (p < 0.02, RR 5.22). Six of 15 patients that were followed for more than on year (40%), were Farr positive. CONCLUSIONS: Elevated anti-dsDNA antibodies measured using Farr technique in patients with inactive generalised lupus erythematosus, predicted the risk of relapse. However less than half of patients with inactive disease and elevated Farr relapsed in a period of one year. The need to treat patients with inactive SLE and positive Farr should therefore be considered debatable.

Influence of the HLA-DR beta shared epitope on susceptibility to and clinical expression of rheumatoid arthritis in Chilean patients.

OBJECTIVE: To analyse the influence of shared epitope positive HLA-DRB1 alleles (QKRAA or QRRAA)) on rheumatoid arthritis (RA) susceptibility and severity in Chileans, a population that exhibits a weak association with HLA-DR4. METHODS: Prevalence of alleles DRB1*01 and DRB1*04 alleles was determined by polymerase chain reaction amplification and sequence specific oligonucleotide hybridisation in 129 RA patients with defined clinical features and in 97 healthy controls. RESULTS: The shared epitope was found in 70 (54%) of the RA patients and in 29 (30%) of controls (odds ratio (OR) = 3; 95% confidence intervals (CI) = 1.5, 5.1; p = 0.0004), and was present in a double dose in 20% of patients versus 4% of controls (OR = 6; 95% CI = 2, 21; p = 0.0009). HLA-DRB1*0403 was the most prevalent DR4 subtype in controls (19%). HLA-DRB1*0403 or *0408 were the alleles most prominently associated with RA, 19% versus 6% in controls (OR = 3; 95% CI = 1.3, 10; p = 0.01). The risk of RA in those carrying a double dose of the shared epitope was 7.5 times that seen in patients lacking the epitope. Disease severity was moderate: 33% had extra-articular manifestations. The double dose was associated with an increased risk of vasculitis or extra-articular manifestations. However, 59 patients (46%) did not carry the shared epitope and 18 of them (31%) had extra-articular manifestations. CONCLUSIONS: The weak association of RA with DR4 in Chileans seems to relate to a relatively high frequency of the DRB1*0403 allele among DR4 subtypes. As in other populations, the shared epitope in double dose is associated with RA development, especially in its more severe forms. However, both development and expression of severe forms of the disease were independent of the shared epitope in a high proportion of patients, thus emphasising the genetic heterogeneity of the disease and the possible involvement of other genetic elements.