SARS-CoV-2 infection in patients with autoimmune rheumatic diseases in northeast Italy: A cross-sectional study on 916 patients.

BACKGROUND: Whether patients with autoimmune rheumatic diseases (ARD) have a higher risk for SARS-CoV-2 infection (COVID-19) and how SARS-CoV-2 pandemic impacts on adherence to therapy has not been fully elucidated. We assessed the rate and clinical presentation of COVID-19, and adherence to therapy in a large cohort of patients with ARD followed-up in a tertiary University-Hospital in Northeast Italy. METHODS: Between April 9th and April 25th, 2020, after SARS-CoV-2 infection peak, a telephone survey investigating the impact of COVID-19 on patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), ANCA-associated vasculitis (AAV), and idiopathic inflammatory myopathies (IIM) was administered. Demographics, disease activity status, therapy, occupational exposure, and adherence to social distancing advise were also collected. RESULTS: 916 patients (397 SLE, 182 AAV, 176 SSc, 111 RA, 50 IIM) completed the survey. 148 patients developed at least one symptom compatible with COVID-19 (cough 96, sore throat 64, fever 64, arthromyalgias 59, diarrhea 26, conjunctivitis 18, ageusia/hyposmia, 18). Among the 916 patients, 65 (7.1%) underwent SARS-CoV-2 nasopharyngeal swab (18 symptomatic and 47 asymptomatic), 2 (0.21%) tested positive, a proportion similar to that observed in the general population of the Veneto region. No deaths occurred. 31 patients (3.4%) withdrew ≥1 medication, mainly immunosuppressants or biologics. Adoption of social distancing was observed by 860 patients (93.9%), including 335 (36.6%) who adopted it before official lockdown. CONCLUSIONS: COVID-19 incidence seems to be similar in our cohort compared to the general population. Adherence to therapy and to social distancing advise was high.

Early Lupus Project: one-year follow-up of an Italian cohort of patients with systemic lupus erythematosus of recent onset.

Objective To describe the clinical and serological features of a prospectively followed cohort of early diagnosed systemic lupus erythematosus (SLE) patients during a one-year follow-up period. Methods SLE patients with disease duration less than 12 months were consecutively enrolled in a multicentre, prospective study. At study entry and then every 6 months, a large panel of data was recorded. Results Of 260 patients enrolled, 185 had at least 12 months of follow-up; of these, 84.3% were female, 92.4% were Caucasians. Mean diagnostic delay was about 20 months; higher values of European Consensus Lupus Activity Measurement (ECLAM) and of organs/systems involved were both associated with shorter diagnostic delay. Clinical and serological parameters improved after study entry. However, patients' quality of life deteriorated and cardiovascular risk factors significantly increased. About one-third of patients with active disease at study entry went into remission (ECLAM = 0). Negative predictors for remission were: oral ulcers, arthritis, low C4, anti-SSB (Ro) antibodies and therapy with mycophenolate. There was a widespread use of glucocorticoids both at baseline and during follow-up. Conclusion Clinical symptoms and serological parameters improve during the first period after diagnosis. However, patients' quality of life deteriorates. The widespread use of glucocorticoids is probably the reason for the early significant increase of some cardiovascular risk factors.

Value and goals of treat-to-target in systemic lupus erythematosus: knowledge and foresight.

Treat-to-target is a therapeutic strategy aimed at improving disease outcome through the achievement of shared treatment goals, which has dramatically ameliorated the prognosis of widespread disorders, such as hypertension or diabetes. Conversely, efforts to delineate treat-to-target in systemic lupus erythematosus (SLE) have failed in pinpointing common goals and treatment strategies, probably because of disease heterogeneity and lack of measurable biomarkers predicting disease course and ensuring a safe treatment tapering during quiescence. Given the detrimental effects of persistent disease activity and protracted corticosteroid therapy on patients' outcome in lupus, disease remission should be pursued whenever possible. Fortunately, clinical remission is currently realistic for a greater number of patients than it was in the past, yet tight monitoring is required in order for patients to benefit from disease- and corticosteroid-free intervals, while minimizing the risk of disease flares. In everyday practice, patients should be brought to the lowest level of disease activity ensuring a significant benefit over a persistently active disease, being either clinical remission or low disease activity.

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.

Diagnostic Biomarkers of Amyloid and Tau Pathology in Alzheimer's Disease: An Overview of Tests for Clinical Practice in the United States and Europe.

Amyloid and tau biomarkers for Alzheimer's disease are widely recognized diagnostic tools for the identification of Alzheimer's disease pathology antemortem and are recommended by the most recent clinical and research guidelines. Approved biomarkers include positron emission tomography (PET)- and fluid-based markers derived from cerebrospinal fluid and, more recently, plasma. These biomarkers are still infrequently used in clinical practice, potentially due to challenges in access to and understanding of individual assay information and methodology. We provide an overview of the diagnostic biomarkers for amyloid and tau pathology that are currently available in the US and/or EU for clinical use. Available performance data from both labels/instructions for use and the scientific literature (with focus on autopsy or PET as standard of truth) are summarized to help healthcare providers navigate the biomarker landscape. All available PET amyloid and tau biomarkers demonstrate high accuracy in identifying amyloid and tau Alzheimer's disease pathology, respectively, at autopsy. Among cerebrospinal fluid biomarkers, all showed accurate prediction of Alzheimer's disease pathology, either based on autopsy or PET findings; greater accuracy was evident for concentration ratios (Aß42/40 or P-tau181/Aß42) versus individual biomarker concentrations. Among plasma biomarkers, Aß42/40 and P-tau181 demonstrated high agreement with PET findings. Overall, we conclude that commercially available PET, cerebrospinal fluid and plasma assays accurately identify Alzheimer's disease amyloid and tau pathology. The recent development of fully automated tests for fluid-based biomarkers improves test reliability. The continued development of plasma biomarkers holds promise for the future management of patients with Alzheimer's disease.

The interferon in idiopathic inflammatory myopathies: Different signatures and new therapeutic perspectives. A literature review.

Idiopathic inflammatory myopathies (IIM), even though sharing common clinical manifestations, are characterized by diversified molecular pathogenetic mechanisms which may account for the partial inefficacy of currently used immunomodulatory drugs. In the last decades, the role of interferon (IFN) in IIM has been extensively elucidated thanks to genomic and proteomic studies which have assessed the molecular signature at the level of affected tissues or in peripheral blood across distinct IIM subtypes. A predominant type I IFN response has been shown in dermatomyositis (DM), being especially enhanced in anti-melanoma differentiation-associated gene 5 (MDA5)+ DM, while a type 2 IFN profile characterizes anti-synthetase syndrome (ASyS) and inclusion body myositis (IBM); conversely, a less robust IFN footprint has been defined for immune-mediated necrotizing myopathy (IMNM). Intracellular IFN signaling is mediated by the janus kinase/signal transducer and activator of transcription (JAK/STAT) through dedicated transmembrane receptors and specific cytoplasmic molecular combinations. These results may have therapeutic implications and led to evaluating the efficacy of new targeted drugs such as the recently introduced janus kinase inhibitors (JAKi), currently approved for the treatment of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. In this review we aim to summarize the most significant evidence of IFN role in IIM pathogenesis and to describe the current state of the art about the ongoing clinical trials on IFN-targeting drugs, with particular focus on JAKi.

Induction of the 'ASIA' syndrome in NZB/NZWF1 mice after injection of complete Freund's adjuvant (CFA).

Adjuvants, commonly used in vaccines, may be responsible for inducing autoimmunity and autoimmune diseases, both in humans and mice. The so-called 'ASIA' (Autoimmune/inflammatory Syndrome Induced by Adjuvants) syndrome has been recently described, which is caused by the exposure to a component reproducing the effect of adjuvants. The aim of our study was to evaluate the effect of injection of complete Freund's adjuvant (CFA) in NZB/NZWF1 mice, a lupus-prone murine model. We injected 10 NZB/NZWF1 mice with CFA/PBS and 10 with PBS, three times, 3 weeks apart, and followed-up until natural death. CFA-injected mice developed both anti-double-stranded DNA and proteinuria earlier and at higher levels than the control group. Proteinuria-free survival rate and survival rate were significantly lower in CFA-treated mice than in the control mice (p = 0.002 and p = 0.001, respectively). Histological analyses showed a more severe glomerulonephritis in CFA-injected mice compared with the control mice. In addition, lymphoid hyperplasia in spleen and lungs, myocarditis, and vasculitis were observed in the former, but not in the latter group. In conclusion, the injection of CFA in NZB/NZWF1 mice accelerated autoimmune manifestations resembling 'ASIA' syndrome in humans.

Polarization of TH2 response is decreased during pregnancy in systemic lupus erythematosus.

This study evaluated some cytokines involved in the Th1-Th2 shift during pregnancy in patients with systemic lupus erythematosus (SLE) and healthy women. Twenty-seven consecutive successful pregnancies in 26 SLE patients and 28 pregnancies in 28 matched healthy subjects, as controls, were enrolled and prospectively studied. Sera obtained at first and third trimesters of pregnancy were tested for IL-1α, IL-1ß, IL-2, IL-6, IL-8, IL-10, IL-12p70, INF-γ, and TNF-α with a highly sensitive, multiplexed sandwich ELISA (SearchLight Human Inflammatory Cytokine Array). Statistics were performed by SPSS package. IL-8 serum levels were higher in the first (P<0.0001) and third (P=0.003) trimesters of pregnancy in SLE patients compared with controls, INF-γ serum levels in the third trimester (P=0.009), and IL-10 serum levels in the first and third trimesters (P=0.055 and P<0.0001, respectively). IL-2 (r=0.524 P=0.010), IL-12 (r=0.549 P=0.007), IFN-γ (r=0.492 P=0.017), and IL-6 (r=0.515 P=0.020) serum levels correlated with disease activity in SLE patients in the first trimester of pregnancy. Cytokine profile was similar in patients with and without lupus nephritis both in the first and in the third trimesters of pregnancy. IL-8 serum levels were lower in patients with a previous diagnosis of antiphospholipid antibody syndrome compared with those without, both in the first and in the third trimesters of pregnancy. In SLE patients, a lower than expected decrease in Th1 cytokine serum levels was observed in the third trimester of gestation which could contribute to a lower Th2 cytokine polarization during pregnancy.

Anti-prothrombin antibodies predict thrombosis in patients with systemic lupus erythematosus: a 15-year longitudinal study.

OBJECTIVE: To evaluate the role of anti-prothrombin (anti-PT) antibodies in predicting thrombosis in patients with systemic lupus erythematosus (SLE). METHODS: An inception cohort of 101 SLE patients (12 males, 89 females; mean age 30 +/- 8 years), was considered. Clinical and laboratory evaluations were regularly performed during a 15-year follow-up (median 108 months) with a special focus on thromboembolic events. Serum samples were collected at time of diagnosis and at least once a year thereafter. IgG and IgM anti-PT, anti-cardiolipin (aCL) and anti-beta(2)glycoprotein I (beta(2)GPI) antibodies were measured by enzyme-linked immunosorbent assay (ELISA); lupus anticoagulant (LAC) was assayed by the dilute Russell's viper venom time and activated partial thromboplastin time tests. The analytical specificity of anti-PT ELISA was investigated. The timing of thrombosis occurrence was calculated using the Kaplan-Meier method. RESULTS: In the 15-year follow-up, thrombosis occurred in 14 out of the 101 patients: venous thrombosis in nine cases and arterial thrombosis in five. IgG and/or IgM anti-PT, anti-beta(2)GPI and aCL antibodies, and LAC activity were detected in ten, nine, seven, and nine cases, with sensitivity for thrombosis of 71.4%, 64.3%, 50% and 64.3%, respectively. Thrombosis-free survival was 90% at 5 years and 85.8% at 10 and 15 years, respectively. Thrombosis was predicted by anti-PT (P = 0.001), anti-beta(2)GPI antibodies (P = 0.002) and LAC activity (P = 0.001). Moreover, the risk of thrombosis progressively increased with the number of positive antiphospholipid antibody tests. The presence of four positive antibody tests was associated with a risk of thrombosis thirtyfold higher than in their absence. CONCLUSIONS: This longitudinal study shows that IgG anti-PT antibodies are predictors of thrombosis in SLE patients.

OxLDL/beta2GPI-anti-oxLDL/beta2GPI complex and atherosclerosis in SLE patients.

It has been demonstrated that atherosclerosis (ATS) is enhanced in autoimmune rheumatic diseases, such as systemic lupus erythematosus (SLE). The reason for this accelerated process is still debatable and, although traditional risk factors are more prevalent in SLE patients than in general population, they do not seem to fully explain the enhanced risk. ATS has the characteristics of an autoimmune chronic disease, involving both the innate and the adaptive immunity. Moreover, it satisfies the four criteria defining an autoimmune disease, proposed by Witebsky and Rose. It has been shown that some autoantibodies, including anti-oxLDL, anti-beta(2)GPI, anti-HSP60/65, and more recently anti-oxLDL/beta(2)GPI, play a key role in the pathogenesis of ATS. However the role of these autoantibodies in accelerated ATS in SLE patients is still controversial. In fact, some of them seem to be proatherogenic and other protective; moreover, it has been demonstrated that induced oral tolerance has a protective role against ATS. We have recently observed that the levels of oxLDL/beta(2)GPI antigenic complexes and their antibodies were higher in patients with SLE than in healthy subjects, but we did not find a clear association between oxLDL/beta(2)GPI complexes and IgG or IgM anti-oxLDL/beta(2)GPI autoantibodies and subclinical ATS in SLE patients. Many other studies are required to explain the role of autoantibodies in the pathogenesis of ATS in SLE patients, because the characteristics of SLE seem to mask their effects for atherogenesis.

Anti-C1q antibodies in pregnant patients with systemic lupus erythematosus.

OBJECTIVE: To study anti-C1q antibodies in pregnant patients with systemic lupus erythematosus (SLE) and to evaluate their prognostic significance for the occurrence of disease flares or pregnancy complications. METHODS: Twenty-one pregnancies in 19 SLE patients prospectively followed were analyzed. Disease activity was evaluated on the basis of the physician's intention to treat and a modified version of the ECLAM index. Anti-C1q and anti-dsDNA antibodies were detected in the sera by an ELISA assay. Antinuclear antibodies, anti-ENA antibodies, anticardiolipin antibodies and lupus anticoagulant were also performed. RESULTS: In all the patients the disease was inactive at the beginning of the pregnancy. Four flares of disease activity were observed in 4 pregnancies (19%) and obstetric complications were encountered in 7 pregnancies (43%). Anti-C1q antibodies were positive in 4 (19%) pregnancies and anti-dsDNA antibodies in 8 (38%). The presence of anti-phospholipid antibodies at the first assessment was correlated with the occurrence of obstetric complications (p<0.05). The presence of anti-C1q and anti-dsDNA antibodies at the first assessment had no prognostic significance for the occurrence of flares or obstetric complications during the course of pregnancy. Although the small number of patients studied did not allow for statistically significant analysis, flares appeared to be more likely to occur in patients presenting with anti-dsDNA or anti-C1q antibodies during pregnancy compared to patients with no changes in these antibody titers (43% vs 8% respectively). CONCLUSIONS: The presence of anti-C1q and anti-dsDNA antibodies does not seem to be prognostic for the occurrence of flares during pregnancy. Further studies are warranted to explore this possibility.

Targeting Neuroinflammation to Treat Alzheimer's Disease.

Over the past few decades, research on Alzheimer's disease (AD) has focused on pathomechanisms linked to two of the major pathological hallmarks of extracellular deposition of beta-amyloid peptides and intra-neuronal formation of neurofibrils. Recently, a third disease component, the neuroinflammatory reaction mediated by cerebral innate immune cells, has entered the spotlight, prompted by findings from genetic, pre-clinical, and clinical studies. Various proteins that arise during neurodegeneration, including beta-amyloid, tau, heat shock proteins, and chromogranin, among others, act as danger-associated molecular patterns, that-upon engagement of pattern recognition receptors-induce inflammatory signaling pathways and ultimately lead to the production and release of immune mediators. These may have beneficial effects but ultimately compromise neuronal function and cause cell death. The current review, assembled by participants of the Chiclana Summer School on Neuroinflammation 2016, provides an overview of our current understanding of AD-related immune processes. We describe the principal cellular and molecular players in inflammation as they pertain to AD, examine modifying factors, and discuss potential future therapeutic targets.

Clinical implications of autoantibody screening in patients with autoimmune myositis.

OBJECTIVE: To evaluate the clinical usefulness of serum autoantibody profiling in patients with autoimmune myositis. METHODS: We retrospectively studied 74 consecutive patients: 68 had definite or probable myositis according to Bohan-Peter criteria, six suffered from antisynthetase syndrome with subclinical myopathy. Myositis specific antibodies (MSA) (anti-ARS, -SRP, -Mi-2) were determined by RNA immunoprecipitation or immunoblot, myositis associated antibodies (MAA) (anti-RoRNP, -U1RNP, -PM/Scl, -Ku) by immunoblot. RESULTS: Forty-three patients (58%) were positive for MSA: anti-Jo-1 in 15/27 polymyositis (PM) (55%), 4/33 dermatomyositis (DM) (12%), 1/8 overlap (12%) and 2/6 antisynthetase syndrome (33%); anti-ARS non-Jo-1 in 1/27 PM (4%), 2/33 DM (6%) and 4/6 antisynthetase syndrome (67%); anti-Mi-2 in 1/27 PM (4%) and 11/33 DM (33%); anti-SRP in 3/27 PM (11%) and 1/33 DM (3%). One patient was anti-Jo-1/Mi-2 positive, one anti-Jo-1/SRP positive. Moreover, 27 patients (36%) were positive for MAA: anti-Ro/SSA in 8/27 PM (30%), 7/33 DM (21%), 1/8 overlap (12%), and 3/6 antisynthetase syndrome (50%); anti-U1RNP in 1/27 PM (3.7%), 1/33 DM (3%), and 2/8 overlap (25%); anti-PM/Scl in 2/8 overlap (25%), anti-Ku in 2/8 overlap (25%). Anti-Jo-1 was predominantly associated with PM, anti-Mi-2 was almost exclusively found in DM patients. Anti-ARS antibodies were closely associated with interstitial lung disease and polyarthritis; notably, anti-ARS non-Jo-1 was more frequent in patients without overt muscle alterations. Anti-Ro/SSA antibody was not associated with any disease subset, but significantly more frequent in antisynthetase syndrome. CONCLUSIONS: Searching for MSA and MAA in patients with autoimmmune myositis is recommended because of its diagnostic and clinical value. Anti-ARS non-Jo-1 antibodies seem to preferentially target patients with pulmonary fibrosis without overt myopathy.

Lupus erythematosus and the skin.

Cutaneous manifestations of patients with lupus erythematosus (LE) are very frequent, show a great variety and can occur at any stage of the disease. The most consistent environmental trigger factors so far recognized are exposure to ultraviolet light and certain drug classes known to be capable of inducing LE in otherwise healthy individuals. A classification system has been established including clinical, histologic, photobiologic, serologic, and immunogenetic findings to better define the different cutaneous subtypes of LE. During their clinical evolution, the cutaneous manifestations vary considerably, and, therefore, the diseases which should be considered in differential diagnosis are different, according to the stages of disease development. Furthermore, 25 years of experience worldwide have revealed that individuals whose disease presentation is dominated by subacute cutaneous LE skin lesions and the presence of circulating anti-Ro/SS-A antibodies represent a rather homogeneous immunogenetic subphenotype of LE that enjoys a good prognosis over time. Treatment should be individualized according to disease severity. The majority of patients with cutaneous manifestations of LE do not require systemic immuno-suppressive/ immunomodulatory therapy and the advent of recombinant biologicals has given hope to the small percentage of patients that suffer from particularly severe skin disease activity.

Psoriasis and psoriatic arthritis: immunological aspects and therapeutic guidelines.

Psoriasis is an inflammatory skin disease that affects 1-3% of the European population. Chronic plaque psoriasis, the commonest form of the condition - affecting the majority of patients - usually manifests as red, heavily scaled plaques on elbows, knees, scalp and lower back, but any skin surface may be affected. Psoriasis is associated with an inflammatory sero-negative arthritis, namely "psoriatic arthritis", in approximately 15%of patients with psoriasis and occurs more commonly in people with inflammatory bowel disease such as patients with Crohn's disease. Several studies have demonstrated the role of genetic predisposition, innate and adaptive immunity in the pathogenesis of psoriasis. There is considerable evidence that innate immunity and specifically a dysregulation of the innate immune response is central to the development of psoriasis. The role of TNFalpha is particularly intriguing. The evidence includes further observations that a variety of anti-TNF approaches such as monoclonal antibodies and fusion proteins of soluble TNF receptors are effective therapies both in psoriasis and psoriatic arthritis. In this review, in addition to pathogenetic aspects, some preliminary guidelines for the use of anti-TNFalpha therapy in patients with psoriasis and psoriatic arthritis will be discussed.

The antiphospholipid antibody syndrome: diagnosis, skin manifestations and current therapy.

Antiphospholipid antibody syndrome is characterized by venous and/or arterial thrombosis and/or pregnancy morbidity associated with antiphospholipid antibodies (aPL), such as anticardiolipin antibodies, anti beta 2 glycoprotein I antibodies and positive lupus anticoagulant test. This syndrome may potentially affects any organ system including the skin. Livedo reticularis is the most frequently observed cutaneous lesion; other lesions, by order of frequency, are ulcerations, digital gangrene, subungueal splinter hemorrhages, superficial venous thrombosis, thrombocytopenic purpura, pseudovasculitic manifestations, extensive cutaneous necrosis and primary anetoderma. Skin lesions are more frequently observed in the catastrophic antiphospholipid syndrome, characterized by widespread microvascular occlusions involving multiple organs simultaneously. Patients with antiphospholipid associated thrombosis should receive long-term oral anticoagulants. The intensity of anticoagulation should be guided according to the nature of the thrombotic event (venous vs. arterial thrombosis). Patients with aPL-associated pregnancy morbidity should be treated with aspirin plus heparin and closely monitored during pregnancy. The treatment of the catastrophic antiphospholipid syndrome remains unsatisfactory. High dose intravenous steroids and parenteral anticoagulation should be supplemented by intravenous gammaglobulin and repeated plasma exchanges using fresh frozen plasma early on in the course of the syndrome.

Positive and negative effects of thalidomide on refractory cutaneous lupus erythematosus.

BACKGROUND: Thalidomide is used in cutaneous lupus erythematosus (CLE) refractory to conventional therapies. Peripheral neuropathy (PN) is the most severe side effect, but the incidence of PN and its relation to thalidomide dose are still unclear. OBJECTIVE: To prospectively evaluate the efficacy as well as the occurrence of PN in CLE patients treated with thalidomide, and to assess whether PN, when occurs, correlates with thalidomide dose and/or length of treatment. METHODS: Fourteen female patients with CLE in low-dose thalidomide therapy were followed for up to 24 months. Prior to, and regularly during treatment patients underwent rheumatological, dermatological, neurological and electrophysiological evaluations. A decline in sural SNAP of 50% or more from baseline value was considered as criterion of sensory axonal PN. RESULTS: All patients showed a dramatic improvement of skin manifestations. Ten patients (71.4%) developed a sensory axonal PN. The median time free from this complication was 14 months. No correlations were found between age of the patients nor thalidomide cumulative dose and occurrence of PN (Mann-Whitney U Test; p>0.16). Other adverse effects were: tremor, paresthesias, somnolence, amenhorrea, constipation and thoracic pain. CONCLUSIONS: Low does thalidomide is efficacious in treating CLE, but PN is a common complication whose occurrence does not seem to correlate with total thalidomide dose, whereas with the duration of therapy. A closer electrophysiological follow-up is therefore recommended in the long-term treatment.

[Myositis specific and myositis associated autoantibodies in idiopathic inflammatory myopathies: a serologic study of 46 patients]. / Gli anticorpi miosite specifici e miosite associati nelle miopatie infiammatorie idiopatiche: studio sierologico di 46 pazienti.

OBJECTIVE: To characterize serum autoantibody profiles of patients with idiopathic inflammatory myopathies (IIM) by searching for myositis-specific (MSA) and myositis-associated (MAA) antibodies with sensitive and specific laboratory tests. METHODS: We tested the sera from 46 Caucasian patients diagnosed as affected with IIM at the Division of Rheumatology of Padova University (21 polimyositis, PM; 22 dermatomyositis, DM; 3 myositis overlap syndrome). All patients had definite IIM according to the criteria of Bohan-Peter. MSA including anti-tRNA synthetase (anti-Jo-1 and others) and anti-Mi-2 were determined by RNA immunoprecipitation and a modified immunoblot test, respectively. MAA (-U1RNP, -U2RNP, RoRNP, PM/Scl, Ku) were detected by counterimmunoelectrophoresis and immunoblot. RESULTS: Serum MSA and/or MAA were found in 30/46 (65%) patients with IIM. Twenty-three patients (50%) were positive for at least one MSA: anti-Jo-1 in 15 (33%), anti-Mi-2 in 6 (13%), and other anti-tRNA synthetase in 3 (6%). One patient was anti-Jo-1/Mi-2 positive. Moreover, 18 patients (39%) were positive for at least one MAA: anti-Ro/SSA in 13 (28%), anti-U1RNP in 4 (9%), anti-PM/Scl in 1 (2%) and anti-Ku in 1 (2%). Coexisting MSA and MAA were observed in 8 patients (17%), anti-Jo-1/SSA positive in most cases. Anti-Jo-1 was predominantly associated with PM (57% in PM vs 14% in DM), whereas anti-Mi-2 was exclusively found in DM patients (27%). Anti-synthetase antibodies were closely associated with interstitial lung disease and polyarthritis; anti-Mi-2 positive DM patients did not have lung involvement. Notably, anti-Ro/SSA antibody was frequently observed and almost equally detected in either PM or DM (about 30%): in more than 50% of cases the antibody was associated with one MSA. CONCLUSIONS: By means of analytically reliable methods, MSA was detected in 50% of our IIM patients. Searching for MSA in patients with IIM is recommended because of its diagnostic and prognostic value.

[Detection of serum anti-B/B' UsnRNP antibodies in patients with connective tissue diseases by immunoblotting]. / Determinazione all'immunoblotting degli anticorpi sierici anti-B/B' UsnRNP nei pazienti con connettiviti.

OBJECTIVE: To investigate the reliability of the immunoblot method in the detection of serum immunoreactivity towards the B/B' polypeptides of U small nuclear ribonucleoproteins (UsnRNP) and to assess the significance of these antibodies in connective tissue disease (CTD) patients. METHODS: We tested the sera of 348 patients with CTD (101 SLE, 51 systemic sclerosis, 53 primary Sjögren's syndrome, 27 poly/dermatomyositis, 15 rheumatoid arthritis and 101 overlap CTD), of 31 matched healthy subjects and 13 patients with primary Epstein-Barr virus (EBV) infection with high titre of IgG anti-EBV antibodies. IgG anti-UsnRNP antibodies were determined by immunoblotting on nuclear extract from Raji cells (an EBV-immortalised human B lymphoid cell line) and Jurkat cells (a human T lymphoid cell line). Anti-dsDNA antibodies were detected by indirect immunofluorescence on Crithidia luciliae and anti-ENA by counterimmunoelectrophoresis. Anti-dsDNA activity and avidity were measured in SLE sera by ELISA with Scatchard analysis. Results were statistically analysed by chi-square and Mann-Whitney tests. RESULTS: A high frequency of anti-B/B' antibodies was found in the sera of CTD patients, confined to SLE (54.4%) and overlap CTD with SLE features (55,2%). Anti-B/B' immune reactivity was closely associated with other anti-UsnRNP specificities, gel precipitating anti-nRNP and anti-P antibodies. Nine out of 15 (60%) anti-B/B' positive/anti-ENA negative lupus sera on Raji blots were confirmed to be positive also on Jurkat blots. The sera from patients with EBV infection provided, on Raji blots, completely different band patterns from those obtained with auto-immune sera. CONCLUSIONS. The Sm B/B' proteins are the predominant or, at least, the most frequently targeted antigens of the UsnRNP auto-immune response in SLE and "lupus-like" overlap CTD. Moreover, anti-B/B' is diagnostically specific for CTD with SLE features. Immunoblotting on human B lymphoid cells is a reliable method, in terms of sensitivity and specificity, for the detection of anti-Sm B/B' antibodies.