Genetic risk factors of thrombosis in the antiphospholipid syndrome

The possibility of a genetic predisposition to develop antiphospholipid syndrome (APS) and to produce anticardiolipin antibodies and lupus anticoagulant has been addressed by family studies and population studies. Various studies suggest a familial occurrence of anticardiolipin antibodies and lupus anticoagulant, with or without clinical evidence of APS. This familial tendency could be genetically determined. Multiple human leucocyte antigen-DR or -DQ associations with antiphospholipid antibodies have been described. Genetic studies of a representative antigen, beta2-glycoprotein-I (β₂GPI), have been carried-out and a particular valine²⁴⁷/leucine polymorphism could be a genetic risk for presenting anti-β₂GPI antibodies and APS. Many other thrombosis-related genetic factors have been investigated in APS, but no additional risk for thrombosis has been indicated in affected patients. Although the mechanisms and pathophysiology of thrombosis in APS are highly heterogeneous and multifactorial, different genes and acquired factors seem to be involved. In this review, we will focus on those genetic variants that could contribute to the development of thrombosis in APS.     

Effects of chronic dysthyroidism on activity and exploration

The aim of the present study was to determine the influence of thyroid function on the activity and exploratory behaviour of male Wistar rats. Dysthyroidism was induced by adding drugs to their drinking water from the ninth day of gestation. This method is not as stressful as daily thyroxine injections or thyroidectomy, and therefore did not affect the analysed behavioural patterns. After weaning, the drugs were administered to the young rats until the end of the experiment. Activity and exploration were measured using the Boissier test, a light-darkness test and an open-field test when they were 77 days old. In order to verify that the animals' motor capacity had not been impaired, a psychomotor battery was used. Chronic hyperthyroidism produced a significant increase in activity, but did not affect exploration. On the other hand, hypothyroidism did not affect activity, but did increase exploration. This increase in exploration was observed in activity-independent behavioural parameters, such as head dipping and glancing.     

Efectividad de un programa educativo de rehabilitación respiratoria en atención primaria para mejorar la calidad de vida,la sintomatología y el riesgo clínico de los pacientes con enfermedad pulmonar obstructiva crónica

Aim

To determine the impact of an educational program to improve the management of chronic obstructive pulmonary disease (COPD) that contributes to an increase of the quality of life, exercise capacity, level of dyspnoea, and clinical risk.

Xenotropic Murine Leukemia Virus-Related Virus (XMRV) in Patients with Systemic Lupus Erythematosus

Objectives  

Xenotropic murine leukemia virus-related virus (XMRV)-specific proviral DNA has been recently detected in peripheral blood mononuclear cells of patients with chronic fatigue syndrome. Since chronic fatigue is commonly reported in patients with systemic lupus erythematosus (SLE) we aimed at testing the presence of this virus in these patients.     

Mannose binding lectin and FcgammaRIIa (CD32) polymorphism in Spanish systemic lupus erythematosus patients

OBJECTIVE: Mannose binding lectin (MBL) and FcgammaRII (CD32) polymorphisms have both been implicated as candidate susceptibility genes in systemic lupus erythematosus (SLE). The aim of this study was to evaluate the relationship of these polymorphisms with SLE. METHODS: We studied a cohort of 125 SLE patients from Barcelona, Spain and 138 geographically matched controls. Sequence-specific primer-polymerase chain reaction (SSP-PCR) amplification was used to determine CD32 and MBL structural polymorphisms. MBL haplotypes were established using sequence-specific oligonucleotide probing techniques. RESULTS: Patients carried the MBL codon 54 mutant allele more frequently than controls [odds ratio (OR) 2.2; 95% confidence interval (CI) 1.2-4.0; P=0.007] and the haplotype HY W52 W54 W57 was found to be significantly lower in cases compared with controls (OR 0.6; 95% CI 0.4-0.9; P=0.016). CONCLUSION: The MBL gene codon 54 mutant allele appears to be a risk factor for SLE, whilst haplotypes encoding for high levels of MBL are protective against the disease. Differences between controls and patients were not significant when considering the FcgammaRIIa polymorphisms; similar results were observed for renal affectation.     

Antiphosphatidylethanolamine antibodies contribute to the diagnosis of antiphospholipid syndrome in patients with systemic lupus erythematosus

OBJECTIVE: To evaluate the correlation between antiphosphatidylethanolamine antibodies (aPE) and some antiphospholipid antibodies (aPL)-related clinical manifestations in patients with systemic lupus erythematosus (SLE). METHODS: Patients with SLE (n=217) were tested for the presence of aPE, anticardiolipin antibodies (aCL), and lupus anticoagulant (LA). The prospective aPL-related clinical manifestations studied were: thrombosis, thrombocytopenia, recurrent fetal losses, heart valvulopathies, hemolytic anemia, livedo reticularis, and pulmonary hypertension. RESULTS: A total of 109 SLE patients (50.23%) were IgG aPE-positive; 17.51% presented aPE as the sole autoantibody and had some clinical features of aPL-related clinical manifestations. IgG aPE were associated to the presence of heart valvulopathies (p=0.002). A statistical difference was also found when considering high levels of IgG aPE (O.D.>0.600) in patients with livedo reticularis (p=0.008). CONCLUSION: The evaluation of IgG aPE may allow us to detect some more patients with aPL-related clinical manifestations in the SLE population, aPE correlated particularly with valvulopathies and livedo reticularis.     

Antihistone and anti-double-stranded deoxyribonucleic acid antibodies are associated with renal disease in systemic lupus erythematosus

PURPOSE: We sought to assess the nephritogenic antibody profile of patients with systemic lupus erythematosus (SLE), and to determine which antibodies were most useful in identifying patients at risk of nephritis. METHODS: We studied 199 patients with SLE, 78 of whom had lupus nephritis. We assayed serum samples for antibodies against chromatin components (double-stranded deoxyribonucleic acid [dsDNA], nucleosome, and histone), C1q, basement membrane components (laminin, fibronectin, and type IV collagen), ribonucleoprotein, and phospholipids. Correlations of these antibodies with disease activity (SLE Disease Activity Index) and nephropathy were assessed. Patients with no initial evidence of nephropathy were followed prospectively for 6 years. RESULTS: Antibodies against dsDNA, nucleosomes, histone, C1q, and basement membrane components were associated with disease activity (P <0.05). In a multivariate analysis, anti-dsDNA antibodies (odds ratio [OR] = 6; 95% confidence interval [CI]: 2 to 24) and antihistone antibodies (OR = 9.4; 95% CI: 4 to 26) were associated with the presence of proliferative glomerulonephritis. In the prospective study, 7 (6%) of the 121 patients developed proliferative lupus glomerulonephritis after a mean of 6 years of follow-up. Patients with initial antihistone (26% [5/19] vs. 2% [2/95], P = 0.0004) and anti-dsDNA reactivity (6% [2/33] vs. 0% [0/67], P = 0.048) had a greater risk of developing proliferative glomerulonephritis than patients without these autoantibodies. CONCLUSION: In addition to routine anti-dsDNA antibody assay, antihistone antibody measurement may be useful for identifying patients at increased risk of proliferative glomerulonephritis.     

Predictors of poor renal outcome in patients with lupus nephritis treated with combined pulses of cyclophosphamide and methylprednisolone

Lupus nephritis remains a major cause of morbidity and mortality in patients with systemic lupus erythematosus. Although the renal prognosis has improved, the optimal therapeutic regime has not been definitively established, and significant challenges remain in the management of disease progression and recurrent renal relapse. We performed a prospective study to evaluate the outcome of 38 patients with severe lupus nephritis treated with standard cyclophosphamide and methylprednisolone pulse therapy, and to determine the variables associated with poor outcome. Five patients developed end-stage renal disease (ESRD) (13%), 10 (26%) developed persistent proteinuria (> 1 g/24h) and 15 (39%) suffered at least one relapse after 8 years of follow-up. A high chronicity index, interstitial fibrosis (P = 0.04), persistent hypertension (P < 0.0001) and hypocomplementaemia (P = 0.002) after treatment were the major variables associated with ESRD. Tubular atrophy (P = 0.01), persistent hypertension (P = 0.0001) and hypocomplementaemia after treatment (P = 0.0281) were associated with persistent proteinuria. Persistence of anti-dsDNA antibodies and hypocomplementaemia after treatment (P = 0.0118) were associated with renal relapse. Our data suggest that the group of patients with persistence of hypocomplementaemia and raised anti-dsDNA antibodies titres are at high risk of renal relapse and may be candidates for continuation of immunosuppressive treatment. Patients with persistent proteinuria alone or a high chronicity index are less likely to respond to immunosuppression, and strict control of the hypertension may be the best approach.