Differential expression pattern of microRNAs in CD4+ and CD19+ cells from asymptomatic patients with systemic lupus erythematosus.

OBJECTIVE: The aim of this study was to investigate the pattern of microRNA (miRNA) expression in CD19+ and CD4+ cells from asymptomatic patients with systemic lupus erythematosus (SLE). METHODS: A screening of the expression of 377 miRNAs was performed in human CD4+ and CD19+ cells isolated from the peripheral blood by using a TaqMan Human MicroRNA Array. Validation of differential expression pattern of those was performed using TaqMan assays in these cell populations obtained from a larger cohort of patients and controls. RESULTS: According to the screening assays, three miRNAs were differentially expressed (p value <0.1) in cell populations from both patients and controls: hsa-miR-143, hsa-miR-224 and hsa-miR-576-5p for CD4+ cells, and hsa-miR-10a, hsa-miR-31 and hsa-miR-345 for CD19+ cells. After validation, significant differences (p value <0.05) were confirmed only for hsa-miR-143 and hsa-miR-224 in CD4+ cells and for hsa-miR-10a and hsa-miR-345 in CD19+ cells. In all cases, the miRNAs were over expressed in SLE patients compared with healthy donors. CONCLUSIONS: Our results support a different pattern of miRNA expression in SLE patients.

Screening for PAH in patients with systemic sclerosis: focus on Doppler echocardiography.

It is well established that patients with CTDs such as SSc carry a considerable risk of developing pulmonary arterial hypertension (PAH). Such SSc-PAH patients have an even worse prognosis than patients with only one of these two conditions. In view of the high incidence and prevalence of PAH in SSc, and the available treatment options that improve quality of life, exercise capacity and possibly survival, systematic screening has been recommended. The present article reviews current recommendations from PAH guidelines, focusing on studies that used Doppler echocardiography for screening, and describes limitations associated with the procedure. Furthermore, characteristics and parameters used to identify patients at high risk of developing PAH are summarized.

Registry of the Spanish Network for Systemic Sclerosis: Survival, Prognostic Factors, and Causes of Death.

Systemic sclerosis (SSc) is a rare, multisystem disease showing a large individual variability in disease progression and prognosis. In the present study, we assess survival, causes of death, and risk factors of mortality in a large series of Spanish SSc patients. Consecutive SSc patients fulfilling criteria of the classification by LeRoy were recruited in the survey. Kaplan-Meier and Cox proportional-hazards models were used to analyze survival and to identify predictors of mortality. Among 879 consecutive patients, 138 (15.7%) deaths were registered. Seventy-six out of 138 (55%) deceased patients were due to causes attributed to SSc, and pulmonary hypertension (PH) was the leading cause in 23 (16.6%) patients. Survival rates were 96%, 93%, 83%, and 73% at 5, 10, 20, and 30 years after the first symptom, respectively. Survival rates for diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc were 91%, 86%, 64%, and 39%; and 97%, 95%, 85%, and 81% at 5, 10, 20, and 30 years, respectively (log-rank: 67.63, P < 0.0001). The dcSSc subset, male sex, age at disease onset older than 65 years, digital ulcers, interstitial lung disease (ILD), PH, heart involvement, scleroderma renal crisis (SRC), presence of antitopoisomerase I and absence of anticentromere antibodies, and active capillaroscopic pattern showed reduced survival rate. In a multivariate analysis, older age at disease onset, dcSSc, ILD, PH, and SRC were independent risk factors for mortality. In the present study involving a large cohort of SSc patients, a high prevalence of disease-related causes of death was demonstrated. Older age at disease onset, dcSSc, ILD, PH, and SRC were identified as independent prognostic factors.

[Antiribosomal antibodies and the neurological manifestations in systemic lupus erythematosus]. / Anticuerpos antirribosómicos y manifestaciones neurológicas en el lupus eritematoso sistémico.

BACKGROUND: The possible positive correlation between the presence of antiribosomic antibodies and neurologic and neuropsychiatric manifestations in patients with systemic lupus erythematosus, cited in the literature, was analyzed. METHODS: Neurological involvement (current or previous) was evaluated in 71 successive patients. The anti-ENA antibodies (extractable nuclear antigens) were studied with special attention to the antiribosomic antibodies by: a) indirect immunofluorescence (IFI) on triple rat substrate, Hep2 and Crithidia luciliae; b) counter immunoelectrophoresis (CIE); c) double immunodiffusion (DI), and d) Western blot (WB) in the Molt-4 cell line. The statistical study was performed by the Fisher exact test. RESULTS: RibosomAL dyeing was observed in only 2 patients by IFI on triple rat substrate and HEp2. With CIE and DI, 14 patients (20%) were anti-ENA positive. Detectable bands were obtained with WB in 47 patients (66%) with 9 corresponding to antiribosomic antibodies. No statistical differences were found (p > 0.3) in relation with the presence of antirobosomic antibodies in particular and anti-ENA in general, between the groups with and without neurologic involvement. CONCLUSIONS: No relation was observed between antiribosomic antibodies and neurolupus by determinations of anti-ENA antibodies by Western blot (superior method--p < 0.0001--to direct immunofluorescence, counter immunoelectrophoresis and double immunodiffusion in the comparative study of sensitivity.

[Serologic and molecular HLA typing in patients from Andalucia with Behçet's disease. Genetic and clinical correlations]. / Tipificación HLA serológica y molecular en pacientes andaluces con enfermedad de Behçet. Correlaciones geneticoclínicas.

BACKGROUND: HLA typing was performed in 67 patients with Behçet's disease from Andalucia, Spain to: 1) analyze the association of class I and II molecules with Behçet's disease in Spain; 2) study the clinical correlations and 3) evaluate its diagnostic and/or prognostic role. PATIENTS AND METHODS: 1) Serologic typing (microlymphocytotoxicity): class I molecules in 67 patients and class II molecules in 47 patients (controls: 223 healthy volunteers). 2) Oligotyping (PCR-SSO): class II molecules (DQB1 and generic DRB1) in 47 patients and 189 controls. 3) STATISTICAL ANALYSIS: chi square test (dicotomic variables) and Student t test (continuous variables), and calculation of the relative risk by the Wolff and Haldane formulas. RESULTS: The HLA B51 antigen was the most frequently observed in the whole series (p = 0.003) in males with ocular disease (p = 0.0001) and in patients with cutaneous (p = 0.001) and digestive involvement (p = 0.05). The HLA B51-positive males were younger at disease onset (p = 0.01) with neurologic involvement being infrequent (p = 0.03). The HLA B51 antigen was associated with neurologic (p = 0.06) and articular involvement (p = 0.05). The DQB1*0303 was associated with uveitis of bad evolution (p = 0.01). The DR11 and DQB1*0301 were more frequent in HLA B51-positive patients and the DQ5 was negatively associated with Behçet's disease, particularly in the HLA B51-positive patients. CONCLUSIONS: The study of the HLA antigens provides useful information for the diagnosis of Behçet's disease, aids in differentiating the different clinical forms and has prognostic significance.

[Lymphomatoid granulomatosis: clinicopathologic analysis of 7 cases]. / Granulomatosis linfomatoidea: análisis clinicopatológico de 7 casos.

The aim of the present was to study the possible clinical histological correlations in the cases of lymphomatoid granulomatosis (LG) diagnosed in the last 10 years. Clinic evolutive data were collected in 7 patients diagnosed LG. The histological samples related to the same were revised and an immunohistochemical study was carried out with the oxidase/antiperoxidase technique. Seven patients (5 females and 2 men) with a mean age of 47 years (limit 23-47) were studied. The form of presentation was alteration of the general state in 5 cases accompanied by respiratory symptoms in 4. In 2 cases lung involvement was not found. In 7 biopsies performed at the initiation of the disease, 3 presented characteristics of lymphoma. Three patients are presently alive with a mean follow up time of 31 months and 4 have died (mean survival 17 months). Immunohistochemistry demonstrated T lymphocyte predominance in most of the cases (5 out of 6). The first case of LG in a patient simultaneously infected with the HIV and HTLV-1 is presented. Lymphomatoid granulomatosis possesses a symptomatology which is very inspecific and has histological features which may be superposed to other lymphoproliferative disorders, specially those of the T strain. Given the known relation between HTLV-1 and T lymphomas the role of HTLV-1 in the genesis of LG should be studied in these patients specially in those with the HIV.

[Type I herpes virus, HLA phenotype and Behçet disease]. / Virus herpes tipo I, fenotipo HLA y enfermedad de Behçet.

BACKGROUND: The pathogenic factors of Behçet's disease (BD) differentiate according to geographical zones. The aim of this study was to evaluate the possible relation between this process and infection by type I herpes simplex virus (HSV-1) in Spain. METHODS: The prevalence of antibodies vs HSV-1 and cytomegalovirus (CMV) was studied by complement fixation in three series: A) 34 patients with BD; B) 21 with primary uveitis; C) 40 controls. HSV-1 specificity was established by ELISA. HLA typing was performed in 32 individuals from series A. RESULTS: The frequency of anti HSV-1 in A (76%) was greater (p = 0.045) than in C (55%) and B (66%). These differences were more evident when titers equal/superior to 1/64 were considered as positive, with this being a value exceeding the 97.5% percentage of the control series (A = 21%, C = 2%, p = 0.015), specially for the ocular BD subgroup (26%, p = 0.011 with respect to C). The B series did not differ from C (p = 0.88). To the contrary no differences were observed in the distribution of titers vs CMV. Although a greater frequency of anti HSV-1 was observed in HLA-B51+ the differences were not significant (p = 0.09). CONCLUSIONS: The frequency of evaluable titers of anti-HSV-1 is greater in patients with BD (specially with ocular involvement) than in the control series. No association was found between higher titers and HLA PB51+ phenotype.

[Acquired immunodeficiency syndrome in the province of Cádiz. A study of 269 consecutive patients]. / El síndrome de inmunodeficiencia adquirida en la provincia de Cádiz. Estudio sobre 269 pacientes consecutivos.

BACKGROUND: The epidemiological characteristics, clinical manifestations and survival were analyzed in 269 patients with acquired immunodeficiency syndrome (AIDS) diagnosed in the province of Cadiz up to June 1970. METHODS: A multicenter protocol study including the 7 hospitals attending practically all of the population of the area of Cadiz was carried out. The diagnosis of AIDS was performed according to the 1987 CDC criteria. The Kaplan and Meier actuarial method was used for the survival study. RESULTS: The prevalence was of 10 cases in 1986, 37 in 1987, 61 in 1988, 121 in 1989 and 40 during the first 5 months of 1990. Males dominated (84%) and mean age was of 28.6 years. The predominant risk factor was parenteral drug abuse (84%) with signs of social unacceptance (unemployment 70% and with prison records 68%). Thirty eight percent of the patients were no longer drug addicts at the time of diagnosis. The number of cases of women who acquired the disease through heterosexual transmission has increased over the last 2 years (13 cases). Opportunistic infections made up 93% of the diagnostic criteria with esophageal candidiasis (EC) (45%) and extrapulmonary tuberculosis (ET) (34%) being the most frequent. The probability of survival was 14% at 35 months. When ET was the exclusive diagnostic criteria, survival was higher (30% vs 9%) and the mean of T4 lymphocytes in this group was higher (228 vs 154), all being statistically significant. CONCLUSIONS: AIDS is a serious, progressive problem of the Public Health Department in the province of Cadiz and predominantly affects parenteral drug addicts with a percentage higher than other Spanish series in socially unaccepted people. The increase in the cases of women with AIDS from heterosexual transmission is worrisome. EC and ET are the most verified diagnostic criteria. The prognosis of AIDS remains bad at short term, with survival being greater in those patients with ET as the exclusive criteria due to lesser cellular immunodeficiency.