17-ß-estradiol affects BLyS serum levels and the nephritogenic autoantibody network accelerating glomerulonephritis in NZB/WF1 mice.

Systemic lupus erythematosus (SLE) is an autoimmune disease that predominantly affects fertile women, suggesting sex hormones are involved in disease pathogenesis. B lymphocyte stimulator (BLyS) has been found to be elevated in SLE patients and to drive a lupus-like syndrome in transgenic mice. Our aim was to evaluate the effects of estrogen administration on BLyS and nephritogenic anti-C1q and anti-dsDNA antibodies in lupus-prone NZB/WF1 mice. We implanted pellets releasing 17-ß-estradiol (18.8 µg/day) on the back side the ear of 10 NZB/WF1 mice (group 1), and compared them with 10 mice intraperitoneally injected with PBS 200 µl twice a week (group 2), as controls. We evaluated BLyS, anti-dsDNA and anti-C1q serum levels starting one week after pellet implantation. We also analyzed time to proteinuria onset, proteinuria-free survival and overall survival. Kidneys, spleen, liver and lungs were harvested for histological analysis. Mice were bred until natural death. BLyS serum levels were higher in group 1 than in group 2 mice at each evaluation. Group 1 mice developed nephritogenic antibodies and proteinuria significantly earlier and at higher levels than controls. Direct correlation between BLyS and anti-C1q (R (2 )= 0.6962, p < 0.0001) or anti-dsDNA (R (2 )= 0.5953, p < 0.0001), and between anti-C1q and anti-dsDNA autoantibodies (R (2 )= 0.5615, p < 0.0001) were found. Proteinuria-free and global survival rates were significantly lower in group 1 than in controls. Histological analyses showed more severe abnormalities in group 1 mice. Estrogen administration is associated with increased levels of BLyS as well as of anti-C1q and anti-dsDNA antibodies, leading to accelerated glomerulonephritis and disease progression in NZB/WF1 mice.

Assessment of patients with idiopathic inflammatory myopathies and isolated creatin-kinase elevation.

Idiopathic inflammatory myopathies (IIM) are a group of diseases characterized by inflammation of the skeletal muscle. Weakness, mainly affecting the proximal muscles, is the cardinal muscular symptom in IIM. In patients with dermatomyositis, peculiar skin lesions are observed. The assessment of patients with IIM includes clinical and laboratory evaluation, and clinimetric measurements. Different tools have been proposed to measure muscular and extramuscular disease activity and damage in patients with IIM. A core set of measurements to use in clinical practice was recently proposed. Among laboratory features the increase of serum creatine kinase (CK) is considered a hallmark of muscle inflammation/damage. However, subjects with persistent CK elevation, without any evidence of a definite myopathy, are often seen in clinical practice and need a careful assessment. Indeed, CK blood levels can also increase in non-myopathic conditions, e.g. in case of intense physical exercise, assumption of some drugs (statins), muscular dystrophy, muscular trauma or in case of neuro-muscular disorders which all should be considered in the diagnostic work-up. The assessment of patients with IIM and hyperCKemia will be discussed in this paper.

Premature coronary heart disease in SLE: can we prevent progression?

Patients with systemic lupus erythematosus (SLE) have a higher prevalence of clinical and subclinical atherosclerosis compared with age- and sex-matched controls. Atherosclerosis progression is also accelerated in SLE, and coronary heart disease (CHD) is a major cause of morbidity and mortality. Traditional cardiovascular (CV) risk factors, including hypertension, diabetes mellitus or dyslipidemia, are more prevalent in SLE patients than in the general population, but they cannot fully account for accelerated atherosclerosis in SLE. In fact, a number of nontraditional risk factors have been identified, including disease activity, damage and various treatments. Preventive strategies for CHD are mandatory in SLE patients and should include giving up smoking; performing regular physical activity; managing metabolic abnormalities such as dyslipidemia, insulin resistance, and diabetes; treating persistent disease activity; and minimizing chronic exposure to corticosteroids. Low-dose aspirin, angiotensin-converting enzyme (ACE) inhibitors, vitamin D supplementation, antimalarials and, when indicated, some immunosuppressants such as mycophenolate mofetil should also be considered.

Autoinflammation and autoimmunity: bridging the divide.

As soon as autoinflammatory diseases (AIDs) emerged as new entities, they have been linked to the well known world of autoimmunity. In fact, AIDs and systemic autoimmune diseases (ADs), share some characteristics: they start with the prefix "auto" to define a pathological process directed against self; they are systemic diseases, frequently involving musculoskeletal system; both include monogenic and polygenic diseases. From the pathogenetic point of view, they are characterized by a chronic activation of immune system, which eventually leads to tissue inflammation in genetically predisposed individuals. Nevertheless, the specific effectors of the damage are different in the two groups of diseases: in AIDs the innate immune system directly causes tissue inflammation, whereas in ADs the innate immune system activates the adaptive immune system which, in turn, is responsible for the inflammatory process. Mutations in inflammasome-related proteins, particularly in NOD-like receptor (NLR) genes, have been strongly associated to the occurrence of AIDs, whereas the link between inflammasome and ADs is less clear. However, a role for this multiprotein-complex in some ADs can be postulated, since a wide spectrum of endogenous danger signals can activate NLRs and inflammasome products, including IL-1ß, can activate adaptive immunity. An association between single nucleotide polymorphisms (SNPs) localized in the inflammasome gene NLRP1 and systemic lupus erythematosus has recently been reported. AIDs and ADs are currently subdivided into two different groups, but looking at their similarities they might be considered as a single group of diseases with a large immune pathological and clinical spectrum which includes at one end pure ADs and at the other end pure AIDs.

Atherosclerosis in psoriatic arthritis.

The atherosclerotic process is accelerated in several autoimmune rheumatic diseases. Effector cells of innate and adaptive immunity along with pro-inflammatory cytokines and other immune mediators are found in atherosclerotic lesions, where they play an important role in induction, progression and rupture of plaques. Psoriatic arthritis (PsA) is a chronic inflammatory disease, characterized by arthritis, enthesitis, dactilytis, osteitis, and axial involvement, along with skin manifestations. PsA is frequently associated with obesity, diabetes, dyslipidemia, hypertension, accelerated atherosclerosis and with increased cardiovascular morbidity and mortality. Disease-specific and traditional risk factors seem to account for the atherosclerotic burden in PsA patients. Some immunological factors which are involved in PsA can also contribute to atherosclerosis including C reactive protein (CRP), TNF-α, IFN-γ, IL-1, Il 6, IL23, and Th17.

Anti-annexins autoantibodies: their role as biomarkers of autoimmune diseases.

Annexins are a group of 12 highly conserved proteins which exert several regulatory functions on cell biology. There are involved in numerous cell processes including vesicle trafficking, calcium signaling, cell growth, division, and apoptosis. Autoantibodies directed toward annexin I, II, V and XI have been reported, but their role and their clinical correlates are controversial. Annexin I exerts an anti-inflammatory effect by suppressing the generation of inflammatory mediators and anti-annexin I antibodies were detected in patients affected with rheumatoid arthritis, systemic (SLE) and cutaneous lupus erythematosus. Annexin II and V have a high affinity for phospholipids playing a pivotal role in the regulation of coagulation cascade. Anti-annexin II and anti-annexin V antibodies were found in patients with arterial or venous thrombosis, especially in those with autoimmune rheumatic diseases (ARD) such as SLE, primary antiphospholipid syndrome (APS) or systemic sclerosis. Anti-annexin V antibodies were also found in patients with pregnancy loss with or without APS. Annexin XI is involved in several biological pathways, particularly apoptosis and cell proliferation. Anti-annexin XI antibodies have been found in patients with SLE, undifferentiated connective tissue disease, rheumatoid arthritis, Sjögren's syndrome and APS. The metanalysis of studies published up to now showed that the Odds Ratio for having an ARD in anti-annexin XI positive patients was 5.08 (95% CI 2.06-12.58).

Síndrome de secreción inadecuada de hormona antidiurética por fármacos / Syndome of inappropriate antidiuretic hormone secretion

El síndrome de secreción inadecuada de hormona antidiurética o vasopresina (SIADH) es una entidad de etiología muy variada que cursa con hiponatremia, hipoosmolalidad plasmática, osmolalidad urinaria inadecuadamente elevada y natriuresis altas. Al tratarse de un diagnóstico por exclusión, se precisa descartar previamente estados que cursan con disminución de la volemia eficaz, y polidipsia primaria. Además, el estado ácido-base, el potasio, la función cardiaca, renal, suprarrenal y tiroidea deben ser normales. Junto con las neoplasias e infecciones, los fármacos son una causa habitual, y con incidencia en aumento, de este síndrome. Tanto su diagnóstico como su tratamiento suelen ser poco complejos, y conciernen con frecuencia al ámbito de la Atención Primaria. Se describen cuatro casos de SIADH atribuido a fármacos, y se revisan las características generales de la entidad (AU)

The syndrome of inappropriate antidiuretic hormone (or vasopressin) secretion (SIADH) has a very varied aetiology which presents with hyponatraemia, low plasma and urine osmolality, and an inappropriately high natriuresis. on being a diagnosis by exclusion, it is important to rule out states that present with decreased effective blood volume, and primary polydipsia. In addition, the acid-base, potassium, cardiac, renal, adrenal and thyroid function should be normal. Along with malignancies and infections, drugs are a common and increasing cause of this syndrome. Its diagnosis and treatment are often straightforward, and are often dealt with in primary care. We describe four cases of SIADH attributed to drugs, and review the general characteristics of the condition (AU)