Cardiac involvement in systemic sclerosis: differences between clinical subsets and influence on survival.

Cardiac involvement (CI) is a known complication of SSc associated with increased mortality. Our objective was to describe a cohort of patients with SSc and CI and to assess the differences between cutaneous subsets regarding their presentation and survival. Three hundred and ninety-three Spanish patients from a single center, diagnosed with SSc, were retrospectively studied for evidence of CI using noninvasive and invasive tests from 1976 to 2011. Clinical, epidemiological, immunological and therapeutic features of patients with CI were compared to those without it and within the different cutaneous subsets of SSc. CI was present in 173 (44 %) patients. Mitral regurgitation (67 %), conduction alterations (45 %) and left ventricle diastolic dysfunction (40 %) were the most common findings. Pericardial involvement and heart failure were more frequent in diffuse SSc (dcSSc) than in limited or sine scleroderma SSc. CI accounted for 20 % of deaths, and it was an independent mortality risk factor (HR 2.1, P = 0.02), but once CI was established, classical dcSSc mortality risk factors determined mortality. Patients with dcSSc developed CI faster than limited (HR 1.9, P = 0.003) or sine SSc patients (HR 2.5, P = 0.002), specially during the first year after SSc onset. We found statistically significant differences between the 3 SSc subsets in the presentation of pericardial involvement and heart failure. CI increased the mortality and appeared at a higher rate, especially during the first year after SSc onset. Screening for heart involvement should be performed at diagnosis and during follow-up.

Delayed diagnosis of late-onset Pompe disease in patients with myopathies of unknown origin and/or hyperCKemia.

Pompe disease is a rare metabolic myopathy whose diagnosis is sometimes delayed despite being essential for improving clinical outcomes. We aimed to investigate the prevalence of late-onset Pompe disease among patients with a myopathy of unknown etiology, including polymyositis, or with idiopathic rise of creatine kinase (CK) levels, in a department of internal medicine. A cohort study was conducted in 241 subjects: 140 patients with myopathies of unknown origin or increased CK levels, 30 with polymyositis and 71 who constituted the control group of other myopathies. Acid α-glucosidase (GAA) activity was tested in dried blood spots. If a positive result was obtained, GAA activity in isolated lymphocytes and/or genetic testing was performed as a confirmatory diagnosis. Out of the 140 investigated patients, 2 patients with myopathies of unknown origin were confirmed to be positive for Pompe disease. Thus, late-onset Pompe disease should be considered among adult patients with myopathy of unknown origin.

Pleural irregularity, a new ultrasound sign for the study of interstitial lung disease in systemic sclerosis and antisynthetase syndrome.

OBJECTIVES: To evaluate a new ultrasound sign, pleural irregularity (PI), for the study of interstitial lung disease (ILD) in patients with systemic sclerosis (SSc) and antisynthetase syndrome (ASS). METHODS: The study included patients from our SSc and ASS cohorts with varying degrees of ILD, enrolled from 2011 to 2014. Chest high-resolution computed tomography (HRCT), pulmonary function tests (FVC and DLCO) and chest sonography were performed in each patient. Ultrasound PI and B-lines were quantified using a 72-sonographic point score and HRCT lung abnormalities were quantified using Warrick and Wells scores and categorised through Goh's algorithm. PI was correlated with HRCT and pulmonary function test parameters and its diagnostic performance to detect and classify the extent of ILD was evaluated and compared with B-lines. RESULTS: Thirty-seven patients were studied, 21 with ASS and 16 with SSc (8 without ILD). PI correlated with the Warrick score both in SSc (r=0.6, p=0.01) and ASS patients (r=0.6, p=0.005), showing a higher performance to detect ILD than using B-lines (p=0.01). In SSc patients PI also correlated with Wells score (r=0.7, p<0.001) and with DLCO (r=-0.5, p=0.05), showing a high diagnostic value for detecting ILD (AUC=0.85, 95% CI 0.64-1) and classifying it into limited or extensive (AUC=0.81, 95% CI 0.57-1). A modification of the Goh algorithm including PI was developed as a screening tool to avoid the use of HRCT in SSc patients without ultrasound evidence of extensive ILD. CONCLUSIONS: PI is useful for evaluation of ILD in SSc and ASS patients, and can be incorporated into a diagnostic algorithm in SSc patients to reducing the need for exposure to ionising radiation.

Neutrophil gelatinase-associated lipocalin as a biomarker for lupus nephritis.

BACKGROUND: One of the challenges of treating patients with lupus nephritis (LN) is to accurately assess disease activity and predict its outcome. Since renal-biopsy cannot be performed routinely, new surrogate biomarkers are needed. METHODS: We evaluated neutrophil gelatinase-associated lipocalin (NGAL), to predict renal outcome in LN. Serum and urinary NGAL levels, measured by the enzyme-linked immunosorbent assay, and the fractional excretion (FE) of NGAL relative to the FE of proteins (FE NGAL/FE protein ratio) were determined in a cross-sectional (n = 199) and longitudinal (n = 45) cohort of systemic lupus erythematosus (SLE) patients. Global and renal disease activity was assessed by the SLE disease activity indices, SLEDAI and rSLEDAI, respectively. Correlations between traditional biomarkers were established. Sensitivity, specificity and predictive values of NGAL for renal flare, response to therapy and progression to chronic kidney disease were calculated. RESULTS: The FE NGAL/FE protein ratio exhibited the best sensitivity and specificity to discriminate patients with active LN from those with non-renal flare and inactive SLE. In the prospective study, this biomarker was found to be the best candidate to predict proteinuric flares with an 87% sensitivity and 62% specificity for ratios >14.56 and complete response with a 61% sensitivity and 78% specificity for ratios >26.54 in the presence of a simultaneous worsening or improving rSLEDAIs, respectively. In both conditions, the FE NGAL/FE protein ratio outperformed the anti-dsDNA antibody titres and C3 predictive value. Progression to chronic kidney disease was best predicted by estimated glomerular filtration rate levels, but persistently high levels of serum NGAL (>444.4 ng/mL, P = 0.0001 by Kaplan-Meier) predicted a faster progression. CONCLUSIONS: The FE NGAL/FE protein ratio is a reliable marker of disease activity in patients with SLE and could be used as an indicator of response to therapy, although further studies are required to confirm these results.

Clinical and serological findings associated with the expression of ITGAL, PRF1, and CD70 in systemic lupus erythematosus.

We determined the expression of Integrin alpha L chain (ITGAL), Perforin 1 (PRF1), and CD70 and studied the associations with laboratory and clinical parameters. CD4+ T cells were isolated from 35 SLE patients and 30 healthy controls. The transcript levels of ITGAL, PRF1, and CD70 were quantified by real-time reverse-transcription polymerase chain reaction (RT-PCR). The SLE patients had significantly elevated transcript levels of ITGAL (18.61±22.17 vs. 7.33±9.17, p=0.042), PRF1 (21.67±26.34 vs. 10.67±11.65, p=0.039), and CD70 (1.45±1.63 vs. 0.67± 0.28, p=0.011). Patients with anti-microsomal and/or anti-thyroglobulin antibodies showed high levels of ITGAL (33.41±30.14 vs. 13.58±16.43, p=0.044; and 34.01±27.66 vs. 11.90±16.17, p=0.007, respectively). No association was seen either for the typical antibodies of SLE or for the disease activity. Although ITGAL, PRF1, and CD70 are overexpressed in SLE CD4+ T cells, their expression is not linked to the typical clinical and serological parameters associated with the disease. The role that ITGAL may play in autoimmune thyroiditis deserves further investigation.

Correlation of ultrasound B-lines with high-resolution computed tomography in antisynthetase syndrome.

OBJECTIVES: Interstitial lung disease is a common finding in patients with the antisynthetase syndrome. High-resolution computed tomography is the reference test for diagnosis and follow-up of this condition, but it involves considerable radiation exposure. Our aim was to describe chest ultrasound features and its correlation with high-resolution computed tomography findings in a series of patients with the antisynthetase syndrome. METHODS: The study included patients from our antisynthetase syndrome cohort with varying degrees of interstitial lung disease, consulting in our outpatient clinic over a 1-year period. Chest high-resolution computed tomography and chest sonography were prospectively performed within a 1-week period. High-resolution computed tomography Warrick score was calculated and chest sonography findings (B-lines) at several sonographic points along the anterior and posterior intercostal spaces were semi-quantitatively analyzed. Rho Spearman statistics were applied for possible correlations. RESULTS: Twenty-one consecutive patients were studied. A median of 59 thoracic points was studied per patient (IQR 6); 44.1% (95% CI 29.9-60.7) of them showed at least one B-line. A correlation coefficient of 0.135 (p=0.5) was found between the percentage of ultrasound points with B-lines and the Warrick's score. Only the number of bronchopulmonary segments showing ground glass findings was associated with the percentage of sonographic points with B-lines (Rho=0.5, p=0.02). CONCLUSIONS: A good correlation between the percentage of sonographic points with B-lines and high-resolution computed tomography ground glass opacities was observed in patients with the antisynthetase syndrome.

Calcineurin inhibitors in a cohort of patients with antisynthetase-associated interstitial lung disease.

OBJECTIVES: The aim of this paper is to assess the effect of calcineurin inhibitors (tacrolimus or cyclosporine) for treating patients with interstitial lung disease (ILD) associated with antisynthetase autoantibodies. METHODS: Sixty patients with antisynthetase autoantibodies were identified in our myositis cohort of 179 patients. The medical records of 15 patients with antisynthetase autoantibody-associated ILD treated with tacrolimus/cyclosporine (11 for refractory disease and 4 as first-line therapy) between 1980 and 2011 were retrospectively reviewed. Serial pulmonary function tests were used to assess the clinical response. Qualitative data are presented as a number and percentage, and quantitative data as the median and interquartile range (IQR). RESULTS: Patients were classified as having probable or definite idiopathic inflammatory myopathy (8 dermatomyositis and 4 polymyositis), and pure interstitial lung disease (3 cases). The 15 patients had received tacrolimus/cyclosporine for an average of 19 (IQR 14-30) months. Median age at onset of ILD was 42.3 (IQR 32.4-56.8) years and median duration of lung disease before administration of calcineurin inhibitors was 11 (IQR: 5-49) months. Median duration of follow-up was 24 (IQR 12-32) months. Thirteen patients had anti-histidyl-transfer RNA synthetase autoantibody (anti-Jo-1) and two had anti-alanyl-transfer RNA synthetase autoantibody (anti-PL-12). A more than 10% increase in FVC or stabilisation was observed in 13 (87%; 95%CI 56-98) patients who received calcineurin inhibitors (9 [81%] refractory cases and 4 [100%] as first-line therapy). CONCLUSIONS: Calcineurin inhibitors seem to be a good therapeutic option for managing ILD associated with antisynthetase autoantibodies, not only in refractory cases, but also as first-line treatment.

Usefulness of anti-p155 autoantibody for diagnosing cancer-associated dermatomyositis: a systematic review and meta-analysis.

OBJECTIVE: Anti-p155 autoantibody, which was recently described in adult patients with dermatomyositis (DM), seems to be associated with cancer in this population. We performed a systematic review and meta-analysis to ascertain the accuracy of anti-p155 testing for the diagnosis of cancer-associated myositis. METHODS: We searched relevant databases, with no restrictions on study design or language, for original studies that included adult patients with probable/definite DM or amyopathic DM who were evaluated for neoplasm and anti-p155 status. Pooled sensitivity and specificity were calculated using a bivariate model. We computed the diagnostic odds ratio (OR), likelihood ratios (LRs) for positive and negative test results, positive and negative predictive values, and the summary receiver operating characteristic (SROC) curve. Statistical heterogeneity between studies was assessed using the I(2) statistic, and 95% confidence intervals (95% CIs) were computed for the parameters studied. RESULTS: Six studies including a total of 312 adult patients with DM were selected. The pooled sensitivity of anti-p155 for diagnosing cancer-associated DM was 78% (95% CI 45-94%), and specificity was 89% (95% CI 82-93%). The diagnostic OR was 27.26 (95% CI 6.59-112.82), and LRs for positive and negative test results were 6.79 (95% CI 4.11-11.23) and 0.25 (95% CI 0.08-0.76), respectively. Heterogeneity was substantial except with regard to the LR for a positive test result. The area under the SROC curve was 0.91 (95% CI 0.88-0.93). Taking the pooled prevalence of 17% as pretest probability, anti-p155 had a positive predictive value of 58% and a negative predictive value of 95%. CONCLUSION: Our findings indicate that anti-p155 autoantibody determination is useful for diagnosing cancer-associated myositis and guiding disease management.

Anti-TIF1γ antibodies (anti-p155) in adult patients with dermatomyositis: comparison of different diagnostic assays.

BACKGROUND: A new myositis-specific autoantibody (anti-p155) directed against transcriptional intermediary factor 1 γ (TIF1γ) has been described as a good marker of cancer-associated myositis (CAM). OBJECTIVE: To analyse the feasibility of detecting this autoantibody in patient serum samples using new assays with commercially available recombinant TIF1γ. METHODS: The study included 90 Spanish patients with dermatomyositis (DM), classified as clinically amyopathic DM, CAM, or DM without cancer. Anti-TIF1γ antibodies were detected by ELISA and immunoblot techniques and compared with anti-p155 antibody detection by protein immunoprecipitation assays with radiolabelled HeLa cells. The κ coefficient was used to compare the agreement between the different tests. RESULTS: Serum samples from 23 (25.6%) and 20 (22.2%) patients with DM recognised TIF1γ by ELISA and immunoblot, respectively. ELISA (κ=0.91) and immunoblot (κ=0.88) showed excellent agreement with immunoprecipitation analysis (anti-p155). Good concordance (κ=0.91) was also seen between ELISA and immunoblot. CONCLUSIONS: Excellent agreement was found between anti-p155 detected by immunoprecipitation and anti-TIF1γ detected by ELISA or immunoblot. These data indicate that identification of this autoantibody can be reliably performed in a standard laboratory setting, with potential application in clinical practice for cancer screening in adult patients with DM.

Tacrolimus in the treatment of chronic and refractory late-onset immune-mediated adverse effects related to silicone injections.

BACKGROUND: Although currently not authorized in many countries, medical-grade silicone (MGS) injections have been used for 50 years. Sometimes chronic and severe adverse effects refractory to usual therapy other than corticosteroids appear. OBJECTIVE: To evaluate the effectiveness of tacrolimus in the treatment of refractory cases of late-onset adverse effects related to MGS injections. METHODS: Case-series study of seven patients with late-onset adverse effects related to MGS injections. Cases had been treated with a mean of six drugs with poor response before low-tacrolimus dose was introduced. Patients who had received MGS injections with immediate adverse effects or drug responsiveness were excluded. Patients underwent clinical management and follow-up. RESULTS: Average latency period to onset of symptoms was 65 months (range: 6-144 months). Large, tender, inflammatory nodules; plaques; angioedema; and severe panniculitis were commonly seen. An average of 18 months after tacrolimus administration, five patients were experiencing mild, sparse bouts of inflammatory processes, including nodules, plaques, angioedema, and panniculitis. that were rapidly reversible, and two were in remission. No side effects related to tacrolimus had appeared. CONCLUSION: Tacrolimus is an effective and well-tolerated drug in cases of severe and refractory late-onset inflammatory reactions, including large panniculitis, that complicate silicone gel injections.

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. METHODS: Ninety-five SLE patients, 45 of whom had a Fatigue Severity Scale score higher than 3, were included. Molecular analyses were performed by PCR from DNA obtained from the whole blood of both SLE patients and 50 healthy controls. RESULTS: None of the 145 samples analyzed yielded the specific XMRV PCR product. CONCLUSIONS: We conclude that XMRV is not detected in blood neither from SLE patients nor from healthy controls. It leads to infer that other environmental and biological triggers (different from XMRV) may account for the increased levels of fatigue over the course of SLE.

Venous thromboembolism in patients with dermatomyositis and polymyositis.

OBJECTIVES: To assess the incidence of venous thromboembolic events in dermatomyositis and polymyositis patients, and associated factors. METHODS: We retrospectively studied a cohort of 123 myositis patients (87 dermatomyositis, 36 polymyositis) from a single centre and identified cases with deep vein thrombosis and/or pulmonary embolism. Type of myositis, association with cancer, presence of thrombophilia, disease activity, and intravenous immunoglobulin therapy were analysed. Incidence rates were calculated on the basis of time to first venous thrombotic event. Patients with less than 12 months' follow-up were excluded. RESULTS: Six new first thromboembolic events occurred in 6 of 96 patients studied (6.3%), all with dermatomyositis. Median time to development of venous thromboembolism was 4.3 months (IQR, 0.8-8.8) after the dermatomyositis diagnosis. Venous thromboembolism was significantly associated with intravenous immunoglobulin therapy (p<0.05) and older age (p<0.05), but not with cancer. All events (100%) occurred during active myositis. The incidence density of venous thromboembolism among patients with dermatomyositis according to the first year of follow-up was 9.3 per 1000 person-years (95% CI, 3.4 to 20.3). CONCLUSIONS: A trend toward venous thromboembolism was detected in patients with dermatomyositis.

Age-related survival and clinical features in systemic sclerosis patients older or younger than 65 at diagnosis.

OBJECTIVE: To analyse the differences in SSc clinical features and survival in patients aged > or = 65 years compared with young SSc patients. METHODS: Of a total of 319 SSc patients, we identified 67 (21%) patients aged >65 years. Demographical data such as SSc subsets, the cutaneous complaint, internal organ involvement and the causes of morbidity and mortality were collected. Results of the elderly and young patients were compared. RESULTS: There were 61 (91%) women and 6 (9%) men aged > or = 65 years. The limited SSc (lSSc) subset was more prevalent in elderly than in young patients (74.6 vs 54%, P = 0.002). Pulmonary disease (86.6% in elderly vs 73.8% in young patients, P = 0.034) and cardiac involvement (70.1% in elderly vs 49.6% in young patients, P = 0.004) were significantly more prevalent in elderly patients. In contrast, signs of oesophageal involvement (43.3% in elderly vs 57.5% in young patients, P = 0.040) were less frequent in aged patients. In addition, pulmonary and heart disease appeared significantly earlier after the diagnosis in patients aged > or = 65 years. Mortality was significantly higher in elderly than in young patients (35.8 vs 19%, P = 0.005), but when standardized mortality ratios (SMRs) were analysed, there was no significant mortality increase in the elderly. CONCLUSION: In elderly patients, the lSSc subset is more prevalent than the diffuse. Pulmonary and cardiac involvement are more prevalent in aged patients and appears sooner after the disease diagnosis. SSc is clearly related to increased mortality, although it is not significant in the elderly group.

Molecular mechanisms mediated by human endogenous retroviruses (HERVs) in autoimmunity.

Eight per cent of the human genome is derived from the integration of retroviral sequences that were incorporated in our DNA more than 25 million years ago. Although some of these elements show mutations and deletions, some HERVs are transcriptionally active and produce functional proteins. Different mechanisms have been described which link HERVs to some chronic diseases such as several cancers, nervous system diseases and autoimmune rheumatic and connective tissue diseases. They could cause disease because of their capacity for being moved and inserted next to certain genes whose expression would be consequentially altered. Another way in which disease could potentially arise is when HERV-encoded proteins are expressed. These proteins would be considered as [foreign] and they could trigger B-cells to produce antibodies against them, which, in turn, might cross-react with other proteins of our bodies. This mechanism could give rise to autoimmune diseases such as rheumatoid arthritis (RA), lupus erythematosus, Sjögren's syndrome (SJS), mixed connective tissue diseases and inflammatory neurological disease. Furthermore, it should be pointed out that HERV-proteins may act as superantigens. Interestingly, some environmental agents seem to induce the expression of HERVs. Thus, ultraviolet light and several chemical agents could reactivate such sequences by altering their structure without modifying their nucleotide composition when the methylation pattern is changed. Therefore, the epigenetic changes observed in pathological conditions such as systemic lupus erythematosus (SLE) or cancer could be translated into an effect on the activation of some of the retroelements present in our genome which ultimately could have a direct or indirect role on the initiation and clinical evolution of certain chronic diseases.

Are bacterial growth and/or chemotaxis increased by filler injections? Implications for the pathogenesis and treatment of filler-related granulomas.

BACKGROUND: As microbial agents have been associated with late adverse effects related to fillers antibiotic treatment has been envisaged. OBJECTIVE: To determine whether biomaterials favor bacterial growth and/or attract bacteria. METHODS: Hyaluronic acid, semi-permanent fillers, such as calcium hydroxylapatite, and permanent fillers, such as polyalkylimide/polyacrylamide, were used. Experiments were performed with Escherichia coli, strain HVH-U47. Bacteria were transferred to Sven-Gard agar to test mobility. Striae of this bacterial strain with a MacFarland 1 turbulence pattern were seeded from a spot of inoculated biomaterial using Müller-Hinton medium. The chemoattractive properties of the biomaterials were analyzed 10 days after inoculation. Bacterial growth over the biomaterial and in-depth growth were assessed as well. RESULTS: Semi-permanent fillers did not stimulate bacterial growth but they allowed bacterial colonization over the filler. Permanent acrylic compounds neither presented chemoattractant properties nor showed bacterial growth over the biomaterial. Similar results were obtained when performing in-depth cultures. CONCLUSIONS: Permanent and semi-permanent fillers did not facilitate bacterial growth when flagellated E. coli HVH-U47 was used. Our results do not argue in favor of antibiotics as the mainstay of therapy in late granulomas related to permanent fillers. In the case of resorbable/semi-permanent fillers, more studies are needed before recommending antibiotic therapy.

DNase1 activity in systemic lupus erythematosus patients with and without nephropathy.

The objective of the study is to determine whether the activity of DNase1 is associated to the presence of nephropathy in patients with SLE. Forty-five patients affected with SLE and renal involvement were analyzed. The type of renal involvement was type III or IV glomerulonephritis. At least two serum samples were withdrawn from each patient, one obtained in a renal flare and the other obtained in a period of clinical stability. C3 and C4 complement levels and anti-DNA antibodies were determined. DNase1 activity was measured using a radial enzyme-diffusion method. Results suggest that when comparison of DNase1 activity was established between samples obtained during a phase of active renal involvement and those obtained in the clinically stable phase, we did not find statistically significant differences. When the comparison was performed with matched samples of the same patient, DNase1 activity was lower when patients had active renal involvement than when samples were taken in clinically stable phase (21.21 µg/ml ± 16.47 vs. 25.62 µg/ml ± 18.81, p < 0.05). No difference in DNase1 activity was observed between samples positive or negative for anti-DNA antibodies. No difference in DNase1 activity was found in patients with normal or decreased levels of C3 (25.09 µg/ml ± 17.78 vs. 20.01 µg/ml ± 16.15, p = 0.073) or C4 (23.52 µm/ml ± 16.60 vs. 19.62 µg/ml ± 17.54, p = 0.060). We conclude that low DNase1 activity is associated to the active phase of type III or IV nephropathy. Therefore, it is possible that this enzyme plays an important role in the development of SLE nephropathy.

Anti-annexin A5 antibodies in women with spontaneous pregnancy loss.

BACKGROUND AND OBJECTIVE: The aim was to evaluate the role of anti-annexin A5 (anti-ANXA5) antibodies as risk factor for recurrent miscarriage (RM) and unexplained fetal loss (UFL). PATIENTS AND METHODS: Retrospective, cohort study. SETTING: Vall d'Hebron University Hospital. SUBJECTS: 122 women, in two groups: STUDY GROUP: 54 women with RM/UFL and control group: 68 pregnant without RM/UFL. INTERVENTION: Antiphospholipid, mainly anti-ANXA5 antibody analysis. Comparison of all antiphospholipid antibodies between groups. RESULTS: Antiphospholipid antibody (aPL) prevalence in the study group was 10/54 (14.8%) and 5/68 (7.3%) in control group (p=0.09). In the RM subgroup, it was 3/25 and 9/34 in UFL versus 5/68 in controls (p=0.013). Lupus anticoagulant (LA) was present in 4 cases, all belonging to the study group (p=0.011). Four out of 34 women with UFL were positive for anticardiolipin antibodies-IgG (IgG-aCL) versus 1/68 in controls (p=0.041). In RM subgroup, anti-ANXA5 antibodies were positive in 2/25 versus 3/68 in controls, and in UFL subgroup, 3/34 versus 3/68 cases (p=1.000). CONCLUSION: According to our results, anti-ANXA5 antibodies should not be considered as a risk factor for RM/UFL.

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 (beta(2)GPI), have been carried-out and a particular valine(247)/leucine polymorphism could be a genetic risk for presenting anti-beta(2)GPI 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.

Anti-cyclic citrullinated peptide and anti-keratin antibodies in patients with idiopathic inflammatory myopathy.

OBJECTIVE: To investigate the prevalence of anti-cyclic citrullinated peptide (anti-CCP) and anti-keratin antibodies (AKAs) in a cohort of patients with idiopathic inflammatory myopathy. METHODS: In a cross-sectional study, we determined the presence of anti-CCP and AKAs by ELISA and IIF, respectively, in a cohort of 90 consecutive patients with idiopathic inflammatory myopathy. Associations between anti-CCP and clinical manifestations or other autoantibodies were determined with the chi-square and Mann-Whitney U-tests. Radiographs of hands were retrospectively evaluated. Serum autoantibody profile was determined in all patients. RESULTS: Twelve patients were positive to anti-CCP (13.3%); in eight cases values were moderate-high. AKAs were not detected in any patient. Comparison between patients positive and negative to anti-CCP did not show clinical or biological differences. Arthritis joint erosions or positive status to anti-synthetase antibodies were not more frequent in patients with anti-CCP antibodies. Prevalence of RF was the only variable significantly associated with the presence of these antibodies (P = 0.043). CONCLUSIONS: High titres of anti-CCP can occasionally be found in patients with inflammatory myopathy. Therefore, a possible diagnosis of RA should be considered with caution in these patients.