Clinical features and long-term outcomes of systemic lupus erythematosus: comparative data of childhood, adult and late-onset disease in a national register.

Systemic lupus erythematosus (SLE) affects predominantly women at reproductive age but may present at any age. Age at disease onset has a modulating effect on presentation and course of disease, but controversies persist regarding its impact on long-term outcome. Our aims were to characterize clinical features, co-morbidities and cumulative damage in childhood-onset, adult-onset and late-onset SLE. Patients with childhood-onset SLE fulfilling ACR 1997 criteria were identified in a nationwide register-Reuma.pt/SLE (N = 89) and compared with adult-onset and late-onset counterparts matched 1:1:1 for disease duration. 267 SLE patients with mean disease duration of 11.9 ± 9.3 years were analyzed. Skin (62 %), kidney (58 %), neurological (11 %) and hematologic involvement (76 %) were significantly more common in childhood-onset SLE and disease activity was higher in this subset than in adult- and late-onset disease (SLEDAI-2K 3.4 ± 3.8 vs. 2.2 ± 2.7 vs. 1.6 ± 2.8, respectively; p = 0.004). Also, more childhood-onset patients received cyclophosphamide (10 %) and mycophenolate mofetil (34 %). A greater proportion of women (96 %), prevalence of arthritis (89 %) and anti-SSA antibodies (34 %) were noted in the adult-onset group. There was a significant delay in the diagnosis of SLE in older ages. Co-morbidities such as hypertension, diabetes and thyroid disease were significantly more frequent in late-onset SLE, as well as the presence of irreversible damage evaluated by the SLICC/ACR damage index (20 vs. 26 vs. 40 %; p < 0.001). Greater organ involvement as well as the frequent need for immunosuppressants supports the concept of childhood-onset being a more severe disease. In contrast, disease onset is more indolent but co-morbidity burden and irreversible damage are greater in late-onset SLE, which may have implications for patients' management.

Undifferentiated connective tissue disease: a seven-center cross-sectional study of 184 patients.

The purpose of this study was to characterize the clinical and serological features of a large cohort of patients with antinuclear antibody (ANA) positive undifferentiated connective tissue disease (UCTD). Consecutive patients with UCTD, followed up at the Rheumatology Clinic of the participating centers, were included. Data from these patients were obtained by clinical evaluation and chart review. All patients were diagnosed as having UCTD on basis of the following criteria: positive ANA plus at least one clinical feature of connective tissue disease, but not fulfilling classification criteria for any differentiated connective tissue disease. One hundred eighty-four patients were studied (female patients-94.5%; mean age at time of evaluation-47 years). The most prevalent manifestations were arthralgia (66%), arthritis (32%), Raynaud's phenomenon (30%), sicca symptoms (30%), and leukopenia (19%). The prevalence of ANA was 100%, anti-SSA 20%, anti-dsDNA 14%, and anti-SSB 7%. Patients with anti-dsDNA/anti-Sm, anticentromere/anti-Scl70, or anti-SSA/anti-SSB antibodies more frequently presented a set of manifestations close to systemic lupus erythematosus (SLE), systemic sclerosis, or Sjögren syndrome, respectively. We analyze a large cohort of UCTD. Seventy-two percent of these UCTD patients present lupus-, scleroderma-, or Sjögren-like features but do not fulfill classification criteria and mostly present a mild disease.

[Characterization of a Portuguese population with systemic lupus erytematosus]. / Caracterização de uma população Portuguesa de doentes com lupus eritematoso sistémico.

UNLABELLED: To characterize systemic lupus erythematosus (SLE) in Portuguese patients and to identify differences in diseases expression related to sex and ethnicity. PATIENTS AND METHODS: Retrospective cohort analysis of patients with SLE followed at five Rheumatology Departments between 1976 and 2006. Demographic data, diseases manifestations, medications used, co morbidity and damage scores were recorded. RESULTS: Five hundred forty four patients were studied, 93% female, 89% Caucasians, with an average age at disease diagnosis of 35 years. The most frequent clinical features were musculoskeletal (91%), cutaneous and mucous membrane (90%) and the hematological involvement (58%). Renal diseases and serositis occurred more often in males while myositis was more common in black patients. Immunological features included the presence of anti-nuclear antibodies in 99% of the patients, anti-DNA (76%) anti-SSA (33%), anti-SSB (20%), anti-RNP (26%), anti-Sm (22%), anticardiolipine (31%) and lupus anticoagulant (21%). Anti-SSA, anti-RNP, and anti-Sm antibodies were significantly more prevalent among black patients. The presence and severity of damage measured by SLICC/ACR was similar between sexes and ethnicities. In multivariate analyses diseases duration and the presence of hypertension showed a positive association, while educational and antimalarials were negatively associated with the presence of damage. CONCLUSION: In this cohort of Portuguese patients SLE present clinical features similar to those observed in other predominantly Caucasian populations, albeit a higher prevalence of anti-RNP and anti-Sm antibodies was observed. Some particular features were associated with male sex and African ethnicity. Some socio-demographic and clinical variables were associated with damage accrual.

[Systemic lupus erythematosus and anaemia]. / Lúpus eritematoso sistiémico e anemia.

The authors report the case of a 48-years-old Caucasian women, with a previous diagnosis of systemic lupus erythematosus characterized by asthenia, fever, skin rash, alopecia, Raynaud's phenomenon, arthritis, pericardial effusion, interstitial pulmonary involvement, diffuse proliferative glomerulonephritis with crescents and anemia. The presence of severe anemia refractory to high doses of glucocorticoids (1 mg/ /Kg/day), iron therapy and blood transfusions, associated with a low reticulocyte count determined the execution of a bone marrow aspiration, biopsy and immunophenotyping, which were compatible with the diagnosis of Myelodysplastic Syndrome. The treatment with erythropoietin (5.000U 3x/week) and cyclophosphamide pulses (1 gr/m(2) month) induced complete regression of morphologic bone marrow changes and anemia. The main causes of anemia in lupus patients are discussed.

Influence of human leucocyte antigen-DRB1 on the susceptibility to rheumatoid arthritis and on the production of anti-cyclic citrullinated peptide antibodies in a Portuguese population.

OBJECTIVE: To clarify the influence of the HLA-DRB1 locus on the susceptibility to rheumatoid arthritis and the production of anti-cyclic citrullinated peptide antibodies (anti-CCP) in a Portuguese population. METHODS: 141 patients with rheumatoid arthritis fulfilling the American College of Rheumatology 1987 revised criteria for rheumatoid arthritis were compared with 150 healthy controls. Human leucocyte antigen (HLA)-DRB1 locus genotyping was assessed by polymerase chain reaction reverse probing assays and sequence-specific primers. Anti-CCP antibodies were quantified by ELISA in patients with rheumatoid arthritis. Frequencies between groups were compared by the two-sided Fisher's exact test and considered significant if p<0.05. RESULTS: The HLA-DRB1*04 and HLA-DRB1*10 groups were highly associated with rheumatoid arthritis (p<0.001 and p = 0.031, respectively). High titres of anti-CCP antibodies were largely associated with the presence of HLA-DRB1*04/10. CONCLUSION: The well-recognised susceptibility alleles to rheumatoid arthritis, HLA-DRB1*04, were associated with rheumatoid arthritis in Portuguese patients. The relatively rare DRB1*10 was also associated with rheumatoid arthritis, as was described previously in other southern European countries. Both groups were associated with high anti-CCP titres, reinforcing its relevance to disease onset.

Multiplexed immunoassay for detection of rheumatoid factors by FIDISTM technology.

Our objective was to (i) compare FIDIS Rheuma, a new multiplexed immunoassay designed for simultaneous detection of IgM class rheumatoid factors (RF) directed against Fc determinants of IgG from humans and animals, with agglutination and ELISA (conventional methods) and (ii) evaluate the clinical sensitivity and specificity of biological markers for rheumatoid arthritis (RA). To do this, FIDIS technology was employed using the Luminex system. It consists of distinct color-coded microsphere sets, a flow cytometer, and digital signal processing hardware and software. Agglutination and ELISA tests were performed with commercial kits. The study included 134 samples from RA patients and 105 from healthy blood donors. For human specificity, we compared FIDIS with latex agglutination and ELISA. Relative sensitivities were 98.9% and 88.5% and specificities were 90.2% and 94.6%, respectively. For animal specificity, we compared FIDIS with Waaler-Rose and ELISA. The results were 84.9% and 71.9% for the sensitivities and 97.5% and 98.4% for the specificities, respectively. Detection of IgG anti-CCP by ELISA and IgG antikeratin by immunofluorescence was also determined in order to compare their clinical sensitivity and specificity with IgM-RF, according to the method used. The results were: IgG anti-CCP 72.3%, 97.2%; IgG antikeratin 36.6%, 100%; latex agglutination 66.4%, 97.2%; Waaler-Rose 55.9%, 96.3%; FIDIS human 73.9%, 92.1%; FIDIS animal 49.2%, 97.2%; ELISA human 93.2%, 95.5%; and ELISA animal 74.6%, 91.3%. The results showed the efficiency of FIDIS with analytical performance equivalent to the conventional methods, but having the advantage of giving quantitative results (IU/mL).

Inhibition of hypoxia/reoxygenation-induced apoptosis by an antisense oligonucleotide targeted to JNK1 in human kidney cells.

17-fold) increase in DNA fragmentation. Fluorescence microscopy, using DNA binding dyes, demonstrated that cell death following hypoxia/reoxygenation was due predominantly to apoptosis and not necrosis. Furthermore, reoxygenation, but not hypoxia alone, caused a time-dependent increase in the activation of JNK as monitored by western blot analysis using a phospho-specific JNK antibody. In contrast, p38 mitogen-activated protein kinase was activated following hypoxia, but this activation was not augmented during reoxygenation. Exposure of human kidney cells to a 2'-methoxyethyl mixed backbone antisense oligonucleotide directed against human JNK1 (JNK1 AS) resulted in a potent suppression of JNK mRNA and protein expression, whereas a 6-base mismatch control oligonucleotide was without effect. Moreover, a significant diminution of reoxygenation-induced apoptosis was observed in cells exposed to JNK1 AS but not to the mismatch control oligonucleotide. Taken together, these results strongly indicate that activation of the JNK signaling cascade is a major mechanism whereby hypoxia/reoxygenation induces apoptosis.

The sequence similarity of the Drosophila suppressor of hairless protein to the integrase domain has no functional significance in vivo.

Suppressor of Hairless [Su(H)] plays an essential role in neurogenesis in Drosophila by controlling successive alternative cell fate decisions in the developing adult epidermis. Analysis of the predicted amino acid sequence of the Su(H) protein revealed a weak similarity to the catalytic domain of a family of phage integrases and yeast recombinases. We present here the results of a site-directed mutagenesis of the integrase-related region of Su(H), which indicate that this sequence similarity has no functional significance in vivo. We suggest that the JK-RBP protein, encoded by the mouse homologue of Su(H), does not act as a recombinase, as originally proposed.

[Temporary aspects of aging: a new approach to the problem]. / La temporalità dell'invecchiamento. Note su una possible dimensione progettuale.

Medical, psychologic and social problems are typical of the old age. Usually growing old means organic impair, loneliness and a lower social role; moreover, spatial behavior is completely reduced. The period could be lived and be considered in a different way, although aging is unavoidable. This work suggests that we should consider the passing of time a most comprehensive way. The cyclic, biological time can be replaced by a time which considers and gives expression to everybody's needs and activities. The first aim is to give the elderly a new social role, necessary to avoid a "ecosystemic destabilization". Therefore social workers should supply the aged with a new education at "lived time", as a new therapy form.