Pandemic non-adjuvanted influenza A H1N1 vaccine in a cohort of patients with systemic sclerosis.

Objective: To assess the possible effect of therapy, disease subtype and severity on H1N1 immunogenicity in patients with SSc. Methods: Ninety-two patients and 92 age- and gender-matched healthy controls received adjuvant-free influenza A/California/7/2009 (pH1N1) vaccine. Blood samples were collected immediately before and 3 weeks after vaccination to evaluate antibody responses to the H1N1 virus. Efficacy was assessed by seroprotection (SP) and seroconversion (SC) rates and the factor increase in geometric mean antibody titre. Participants received a 21-day symptom diary card and were instructed to report local and systemic adverse events. Results: SSc patients were predominantly females (91%) and 61% had limited SSc, 12% had severe skin involvement and 57.6% were on immunosuppressive (IS) therapy. SSc patients and controls presented comparable overall SP (P = 0.20) and SC (P = 0.61) rates. Further evaluation of the possible effect of disease and therapy revealed similar rates of SP and SC in patients with dcSSc vs lcSSc (SP P = 0.62 and SC P = 0.66), severe vs mild/moderate skin involvement (SP P = 1 and SC P = 0.45) and with vs without IS (SP P = 0.26 and SC P = 0.10). The frequency of mild local and minor systemic reactions was similar in patients with dcSSC vs lcSSc (P = 0.70 vs 0.32) and in those with and without severe skin involvement (P = 0.59 vs 0.28). Conclusion: The non-adjuvanted influenza H1N1 virus vaccine proved to be safe and effective, independent of SSc clinical subtype, disease severity or therapy. These latter factors do not seem to contribute to mild adverse events observed in SSc. Our data support the annual influenza vaccination recommendation for these patients. Trial registration: ClinicalTrials.gov (http://clinicaltrials.gov), NCT01151644.

Large Artery Dysfunction in Primary Antiphospholipid Syndrome.

OBJECTIVE: The aim of this study was to assess the arterial distensibility of large vessels and changes in microvasculature in primary antiphospholipid syndrome. METHODS: Twenty-two antiphospholipid syndrome (APL) patients and 66 age-, sex-, height-, and blood pressure-matched controls were evaluated. Second derivative of the finger photoplethysmogram (SDPTG) was used as a noninvasive method to evaluate the pulse wave. The b/a and d/a indices, which reflect, respectively, large-vessel and small-vessel properties, were calculated from the SDPTG waveform components. Vascular age index was also determined. RESULTS: Arterial thrombosis occurred in 59.1% (13/22) of APL patients, with a predominance of stroke episodes (61.5%). Venous thromboembolism was observed in 36.4% (all deep venous thrombosis), and obstetric complications in 36.4%. Frequency of diabetes mellitus, smoking, and dyslipidemia was comparable in APL patients and control subjects (P > 0.05). Concerning plethysmography findings, b/a ratio was higher in patients than in control subjects (-0.44 ± 0.16 vs. -0.54 ± 0.18, P = 0.034), whereas d/a ratio (-0.30 ± 0.16 vs. -0.31 ± 0.18, P = 0.83) was comparable. Moreover, SDPTG (-0.16 ± 0.35 vs. -0.30 ± 0.38, P = 0.16) and vascular age index values (53.5 ± 11.6 vs. 51.8 ± 16.1, P = 0.65) were alike in both groups. Regarding disease-related factors, patients with arterial and venous thrombosis had similar b/a, d/a, and vascular age indices (P = 0.95; P = 0.06; P = 0.12, respectively). CONCLUSIONS: The higher b/a ratio in APL patients suggests decreased distensibility of large arteries and may be why APL patients are at higher risk for cardiovascular events. The d/a ratio, that is considered a marker of small vessel vascular resistance, was not different than controls. Further studies are needed to evaluate vascular factors that predispose APL patients to atherosclerotic events.

Reduction of ovarian reserve in adult patients with dermatomyositis.

OBJECTIVES: To assess ovarian reserve markers and anti-corpus luteum (anti-CoL) antibodies in dermatomyositis (DM) patients. METHODS: Forty female DM patients were invited to participate. Exclusion criteria included hormonal contraceptive use within the last six months, neoplasia associations, overlapped systemic autoimmune diseases, current pregnancy, gynaecological surgery and individual choice not to participate. The final experimental group for this cross-sectional study included 16 DM patients and 23 healthy controls, each of whom was evaluated during the early follicular phase of the menstrual cycle. Values for IgG anti-CoL (via immunoblotting), follicle stimulating hormone (FSH), estradiol, inhibin B, anti-Müllerian hormone (AMH) serum levels (via ELISA) and sonographic antral follicle count (AFC) were determined. RESULTS: DM patients and controls were of comparable mean age (p>0.05). The mean age of DM onset was 29.1±4.7 years, with disease duration of 5.6±3.2 years. Menstrual cycle characteristics, comorbidity and lifestyle were similar amongst patients in both groups (p>0.05). AMH values of ≤1ng/mL (p=0.027) and AFC values (p=0.017) were significantly reduced in DM patients relative to the control group, whereas serum estradiol levels (p<0.001) were higher in DM patients compared to controls. In contrast, serum FSH and inhibin B levels, ovarian volumes, and anti-CoL antibody frequency were similar in both groups. Differences in AFC and estradiol were determined to be significant following Bonferroni correction for multiple testing. CONCLUSIONS: We identified a diminished ovarian reserve in DM patients of reproductive age. Further studies are necessary to assess the idiopathic inflammatory myopathy-related factors involved in the ovarian impairment of this patient population.

Evidence for cardiac safety and antiarrhythmic potential of chloroquine in systemic lupus erythematosus.

AIMS: To perform a comprehensive evaluation of heart rhythm disorders and the influence of disease/therapy factors in a large systemic lupus erythematosus (SLE) cohort. METHODS AND RESULTS: Three hundred and seventeen consecutive patients of an ongoing electronic database protocol were evaluated by resting electrocardiogram and 142 were randomly selected for 24 h Holter monitoring for arrhythmia and conduction disturbances. The mean age was 40.2 ± 12.1 years and disease duration was 11.4 ± 8.1 years. Chloroquine (CQ) therapy was identified in 69.7% with a mean use of 8.5 ± 6.7 years. Electrocardiogram abnormalities were detected in 66 patients (20.8%): prolonged QTc/QTd (14.2%); bundle-branch block (2.5%); and atrioventricular block (AVB) (1.6%). Age was associated with AVB (P = 0.029) and prolonged QTc/QTd (P = 0.039) whereas anti-Ro/SS-A and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores were not (P > 0.05). Chloroquine was negatively associated with AVB (P = 0.01) as was its longer use (6.1 ± 6.9 vs. 1.0 ± 2.5 years, P = 0.018). Time of CQ use was related with the absence of AVB [odds ratio (OR) = 0.103; 95% confidence interval (CI) = 0.011-0.934, P = 0.043] in multiple logistic regression. Holter monitoring revealed abnormalities in 121 patients (85.2%): supraventricular ectopies (63.4%) and tachyarrhythmia (18.3%); ventricular ectopies (45.8%). Atrial tachycardia/fibrillation (AT/AF) were associated with shorter CQ duration (7.05 ± 7.99 vs. 3.63 ± 5.02 years, P = 0.043) with a trend to less CQ use (P = 0.054), and older age (P < 0.001). Predictors of AT/AF in multiple logistic regression were age (OR = 1.115; 95% CI = 1.059-1.174, P < 0.001) and anti-Ro/SS-A (OR = 0.172; 95% CI = 0.047-0.629, P = 0.008). CONCLUSIONS: Chloroquine seems to play a protective role in the unexpected high rate of cardiac arrhythmias and conduction disturbances observed in SLE. Further studies are necessary to determine if this antiarrhythmic effect is due to the disease control or a direct effect of the drug.

Anti-ribosomal P protein: a novel antibody in autoimmune hepatitis.

BACKGROUND: Autoantibodies to ribosomal P proteins (anti-rib P) are specific serological markers for systemic lupus erythematosus (SLE) and are associated with liver involvement in this disease. The similarity in autoimmune background between autoimmune hepatitis (AIH) and SLE-associated hepatitis raises the possibility that anti-rib P antibodies might also have relevance in AIH. AIMS: To evaluate the frequency and clinical significance of anti-rib P antibodies in a large AIH cohort. METHODS: Sera obtained at diagnosis of 96 AIH patients and of 82 healthy controls were tested for IgG anti-ribosomal P protein by ELISA. All of the sera were also screened for other lupus-specific autoantibodies, three patients with the presence of anti-dsDNA (n = 1) and anti-Sm (n = 2) were excluded. RESULTS: Moderate to high titres (>40 U) of anti-rib P antibody were found in 9.7% (9/93) of the AIH patients and none of the controls (P = 0.003). At presentation, AIH patients with and without anti-rib P antibodies had similar demographic/clinical features, including the frequency of cirrhosis (44.4 vs. 28.5%, P = 0.44), hepatic laboratorial findings (P > 0.05). Importantly, at the final observation (follow-up period 10.2 ± 4.9 years), the AIH patients with anti-rib P had a significantly higher frequency of cirrhosis compared with the negative group (100 vs. 60%, P = 0.04). CONCLUSION: The novel demonstration of anti-rib P in AIH patients without clinical or laboratory evidence of SLE suggests a common underlying mechanism targeting the liver in these two diseases. In addition, this antibody appears to predict the patients with worse AIH prognoses.

Dyslipidaemia in juvenile dermatomyositis: the role of disease activity.

OBJECTIVES: To evaluate the presence of dyslipidaemia in JDM and its possible risk factors. METHODS: Twenty-five JDM patients were compared to 25 healthy controls according to demographic data, body composition, fasting lipoproteins, glycaemia, insulin, antibodies and muscle enzymes. JDM scores were assessed: CMAS, MMT, DAS, MYOACT and MYTAX. RESULTS: Abnormal lipid profile was found in nine patients and four controls (36% vs. 16%, p=0.196). JDM patients demonstrated significant higher levels of triglycerides (TG) [80(31-340) vs. 61(19-182) mg/dL, p=0.011] and higher frequency of abnormal levels of high density lipoproteins (HDL) (28% vs. 4%, p=0.04) when compared to controls. JDM patients with dyslipidaemia demonstrated significant lower median of HDL levels [29(0-49) vs. 50(39-72) mg/dL, p=0.0005], higher frequency of low HDL levels (77% vs. 0%, p=0.0001), higher TG levels [128(31-340) vs. 69(46-138) mg/dL, p=0.011], and also a higher frequency of increased levels of TG (44% vs. 0%, p=0.01), and TC (33% vs. 0%, p=0.03) when compared to those without this condition. Positive anti-LPL antibody was detected in just one JDM patient with abnormal lipid profile. JDM with dyslipidaemia had higher ESR (26 vs. 1 4.5mm/1sthour, p=0.006), CRP (2.1 vs. 0.4mg/dL, p=0.01), DAS (6 vs. 2, p=0.008), MYOACT(0.13 vs. 0.01, p=0.012), MYTAX(0.06vs.0,p=0.018), and lower scores of CMAS (47 vs. 52, p=0.024) and MMT (78 vs. 80, p=0.001) compared to JDM without dyslipidaemia. Positive correlations were detected between TG levels and CRP (r=0.697, p=0.001), DAS (r=0.610, p=0.001), MYOACT (r=0.661, p=0.001), MYTAX (r=0.511, p=0.008), and negative correlations with CMAS (r=-0.506, p=0.009) and MMT (r=-0.535, p=0.005). No differences were found between these groups regarding body composition, lipodystrophy, anti-LPL antibodies, and treatment except by higher frequency of cyclosporine current use in patients with dyslipidaemia (33% vs. 0%, p=0.03). CONCLUSIONS: Dyslipidaemia in JDM patients was characterised by increased levels of TG and low levels of HDL. Disease activity and cyclosporine use were the mainly factors associated to these abnormalities.

Persistent periodontal disease hampers anti-tumor necrosis factor treatment response in rheumatoid arthritis.

OBJECTIVE: This study aimed to evaluate prospectively the influence and the evolution of periodontal disease (PD) in rheumatoid arthritis (RA) patients submitted to anti-tumor necrosis factor (TNF) therapy. METHODS: Eighteen patients with RA (according to the American College of Rheumatology criteria) were assessed for PD before (BL) and after 6 months (6M) of anti-TNF treatment: 15 infliximab, 2 adalimumab, and 1 etanercept. Periodontal assessment included plaque and gingival bleeding indices, probing pocket depth, cementoenamel junction, and clinical attachment level. Rheumatologic evaluation was performed blinded to the dentist's assessment: demographic data, clinical manifestations, and disease activity (Disease Activity Score using 28 joints [DAS28], erythrocyte sedimentation rate [ESR], and C-reactive protein [CRP]). RESULTS: The median age and disease duration of patients with RA were 50 years (25-71 y) and 94% were female. Periodontal disease was diagnosed in 8 patients (44.4%). Comparing BL to 6M, periodontal parameters in the entire group remained stable (P > 0.05) throughout the study (plaque and gingival bleeding indices, probing pocket depth, cementoenamel junction, and clinical attachment level), whereas an improvement in most analyzed RA parameters was observed in the same period: DAS28 (5.5 vs. 3.9, P = 0.02), ESR (21 vs. 12.5 mm/first hour, P = 0.07), and CRP (7.8 vs. 2.8 mg/dL, P = 0.25). Further analysis revealed that this improvement was restricted to the group of patients without PD (DAS28 [5.5 vs. 3.6, P = 0.04], ESR [23.0 vs. 11.5 mm/first hour, P = 0.008], and CRP [7.4 vs. 2.1, P = 0.01]). In contrast, patients with PD had lack of response, with no significant differences in disease activity parameters between BL and 6M: DAS28 (5.2 vs. 4.4, P = 0.11), ESR (17.0 vs. 21.0, P = 0.56), and CRP (9.0 vs. 8.8, P = 0.55). CONCLUSIONS: This study supports the notion that PD may affect TNF blocker efficacy in patients with RA. The possibility that a sustained gingival inflammatory state may hamper treatment response in this disease has high clinical interest because this is a treatable condition.

Immunogenicity and safety of the 2009 non-adjuvanted influenza A/H1N1 vaccine in a large cohort of autoimmune rheumatic diseases.

BACKGROUND: Despite the WHO recommendation that the 2010-2011 trivalent seasonal flu vaccine must contain A/California/7/2009/H1N1-like virus there is no consistent data regarding its immunogenicity and safety in a large autoimmune rheumatic disease (ARD) population. METHODS: 1668 ARD patients (systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic sclerosis, psoriatic arthritis (PsA), Behçet's disease (BD), mixed connective tissue disease, primary antiphospholipid syndrome (PAPS), dermatomyositis (DM), primary Sjögren's syndrome, Takayasu's arteritis, polymyositis and Granulomatosis with polyangiitis (Wegener's) (GPA)) and 234 healthy controls were vaccinated with a non-adjuvanted influenza A/California/7/2009(H1N1) virus-like strain flu. Subjects were evaluated before vaccination and 21 days post-vaccination. The percentage of seroprotection, seroconversion and the factor increase in geometric mean titre (GMT) were calculated. RESULTS: /st> After immunisation, seroprotection rates (68.5% vs 82.9% p<0.0001), seroconversion rates (63.4% vs 76.9%, p<0.001) and the factor increase in GMT (8.9 vs 13.2 p<0.0001) were significantly lower in ARD than controls. Analysis of specific diseases revealed that seroprotection significantly reduced in SLE (p<0.0001), RA (p<0.0001), PsA (p=0.0006), AS (p=0.04), BD (p=0.04) and DM (p=0.04) patients than controls. The seroconversion rates in SLE (p<0.0001), RA (p<0.0001) and PsA (p=0.0006) patients and the increase in GMTs in SLE (p<0.0001), RA (p<0.0001) and PsA (p<0.0001) patients were also reduced compared with controls. Moderate and severe side effects were not reported. CONCLUSIONS: The novel recognition of a diverse vaccine immunogenicity profile in distinct ARDs supports the notion that a booster dose may be recommended for diseases with suboptimal immune responses. This large study also settles the issue of vaccine safety. (ClinicalTrials.gov #NCT01151644).

Clinical and laboratory features of African-Brazilian patients with systemic sclerosis.

OBJECTIVE: African-Brazilians comprise a group of blacks and "pardos." As racial differences can be associated with distinct presentations, we evaluated the clinical and serological associations of African-Brazilians with systemic sclerosis (SSc). METHODS: Sera from 260 adult SSc patients (203 whites and 57 African-Brazilians) were evaluated. Patients with overlap syndromes were excluded. Clinical and demographic data were obtained from an electronic register database. Laboratory analysis included the following: anti-CENP-A/CENP-B, Scl70, RNA polymerase III, Ku, fibrillarin, Th/To, PM-Scl75, and PM-Scl100 by line immunoassay and anti-nuclear antibodies (ANA) by indirect immunofluorescence (IIF) on HEp-2 cells. RESULTS: African-Brazilian SSc patients presented shorter disease duration (12.8 ± 6.5 vs. 15.9 ± 8.1 years, p = 0.009), higher frequency of nucleolar ANA pattern (28% vs. 13%, p = 0.008), and lower frequencies of centromeric ANA pattern (14% vs. 29%, p = 0.026) and CENP-B (18% vs. 34%, p = 0.017), as well as an association with severe interstitial lung disease (58% vs. 43%; p = 0.044). Further comparison of ethnic groups according to subsets revealed that diffuse SSc African-Brazilian patients presented higher frequency of pulmonary hypertension (p = 0.017), heart involvement (p = 0.037), nucleolar ANA pattern (p = 0.036), anti-fibrillarin antibodies (p = 0.037), and higher mortality (48% vs. 19%; p = 0.009). A different pattern was observed for the limited subset with solely a lower frequency of esophageal involvement (p = 0.050) and centromeric ANA pattern (p = 0.049). Survival analysis showed that African-Brazilians had a higher mortality, when adjusted for age, gender, and clinical subset (RR 2.06, CI 95% 1.10-3.83, p = 0.023). CONCLUSION: African-Brazilians have distinct characteristics according to clinical subset and an overall more severe SSc than whites, similar to the blacks from other countries.Key Points • African-Brazilian SSc patients were associated with severe interstitial lung disease and nucleolar ANA pattern when compared to white SSc patients. • When disease subsets were considered, African-Brazilian patients with diffuse SSc presented association with pulmonary hypertension, heart involvement, nucleolar ANA pattern, and anti-fibrillarin antibodies. • White SSc patients were associated with centromeric ANA pattern. • Survival analysis at 5, 10, 15, and 20 years, adjusted for age, gender, and disease subset, was significantly worse in African-Brazilian SSc patients.

Prevalence of depressive and anxiety disorders in systemic lupus erythematosus and their association with anti-ribosomal P antibodies.

OBJECTIVE: To estimate the prevalence of psychiatric disorders in patients with systemic lupus erythematosus (SLE) and explore their association with anti-ribosomal P (anti-P) antibodies. METHODS: Seventy-one consecutive female SLE patients without neurological manifestations were evaluated for psychiatric disorders using the Structured Clinical Interview for DSM-IV (SCID). Anti-P antibodies were measured by enzyme-linked immunosorbent assay (ELISA)/immunoblot analysis. RESULTS: The mean age of subjects was 34.8 years (SD: 10.1 years), and the mean duration of SLE was 9.8 years (SD: 6.5 years). The 30-day prevalences of psychiatric disorders were: mood disorders 26.8%, anxiety disorders 46.5%, adjustment disorders 8.4%, alcohol abuse 1.4%, and somatoform disorder 1.4%. The lifetime prevalences of psychiatric disorders were: mood disorders 69%, anxiety disorders 52.1%, alcohol abuse 1.4%, and somatoform disorder 1.4%. Subjects with and without psychiatric manifestations did not differ regarding SLE clinical and laboratorial parameters including presence or absence of anti-P antibodies (23.1% vs. 20%, respectively, p=1.0), disease activity, as measured by the Systemic Lupus Erythematosus Disease activity Index (4.08+/-5.7 vs. 4.95+/-6.3 respectively, p=0.60) and cumulated damage, as measured by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (0.7+/-2.3 vs. 0.3+/-0.7 respectively, p=0.33). CONCLUSIONS: Mood and anxiety disorders are the most frequently observed psychiatric disorders in female SLE patients without concomitant neurological manifestations. These mild/moderate forms of psychiatric disorders are not associated with anti-P antibodies in SLE patients. Our findings reinforce the importance of systematic psychiatric evaluation for these patients in order to provide adequate and comprehensive care.

Juvenile idiopathic arthritis activity and function ability: deleterious effects in periodontal disease?

The impact of juvenile idiopathic arthritis (JIA) in periodontal diseases is controversial probably due to gender and age heterogeneity. We therefore evaluated a homogeneous female post-pubertal JIA population for these conditions. Thirty-five JIA patients and 35 gender/age comparable healthy controls were evaluated according to demographic data, complete periodontal evaluation, fasting lipoproteins, and anti-lipoprotein lipase antibodies. JIA scores, laboratorial tests, X-rays, and treatment were also assessed. Current age was similar in JIA patients and controls (11.90 ± 2.0 vs. 12.50 ± 3.0 years, p = 0.289). Complete periodontal assessments revealed that gingival index, dental plaque, gingival bleeding, and clinical dental attachment indices were alike in JIA patients and controls (p > 0.05), except for gingival enlargement in former group (p < 0.0001). Further analysis of patients with and without gingivitis revealed that cyclosporine use was more often observed in JIA patients with gingivitis (37 vs. 0%, p = 0.01), whereas no differences were evidenced in demographic, JIA scores, inflammatory markers, and lipid profile in both groups. Of note, two parameters of periodontal assessment were correlated with JIA scores [gingival index (GI) and Childhood Health Assessment Questionnaire (CHAQ) (r s = +0.402, p = 0.020)] and plaque index (PI) and visual analog scale (VAS) physician (r s = +0.430, p = 0.013). In addition, evaluation of dental assessment demonstrated that JIA activity scores had positive correlation with decayed, missing, and filled teeth (DMF-T) and junvenile athritis disease activity score (JADAS) (r s = +0.364,p = 0.037), VAS physician (r s = +0.401,p = 0.021) and VAS patient (r s = +0.364,p = 0.037). We demonstrated, using rigorous criteria, that periodontal and dental condition in JIA is similar to controls. In spite of that, the finding of a correlation with disease parameters provides additional evidence that increased activity and reduced functional ability underlies the deleterious effect of JIA in oral health.

Lupus anticoagulant: a marker for stroke and venous thrombosis in primary Sjögren's syndrome.

Antiphospholipid antibodies (aPL) and antiphospholipid syndrome (APS) have been described in primary Sjögren's syndrome (pSS) with controversial findings regarding aPL prevalence and their association with thrombotic events. We evaluated 100 consecutive pSS patients (American-European criteria) and 89 age-gender-ethnicity-matched healthy controls for IgG/IgM anticardiolipin (aCL), IgG/IgM anti-beta2-glycoprotein-I (aß2GPI), and lupus anticoagulant (LA) (positivity according to APS Sydney's criteria). Clinical analysis followed standardized interview and physical examination assessing thrombotic and nonthrombotic APS manifestations and thrombosis risk factors. aPLs were detected in 16 % patients and 5.6 % controls (p = 0.035). LA was the most common aPL in patients (9 %), followed by aß2GPI (5 %) and aCL (4 %). Thrombotic events occurred in five patients [stroke in two, myocardial infarction in one and deep-vein thrombosis (DVT) in four], but in none of controls (p = 0.061). Mean age at time of stroke was 35 years. Three patients with thrombotic events (including the two with stroke) had APS (Sydney's criteria) and were positive exclusively for LA. Comparison of patients with (n = 16) and without (n = 84) aPL revealed similar mean age, female predominance, and ethnicity (p > =0.387). Frequencies of livedo reticularis (25 vs. 4.8 %, p = 0.021), stroke (12.5 vs. 0 %, p = 0.024), and DVT (18.8 vs. 1.2 %, p = 0.013) were significantly higher in APL + patients. Conversely, frequencies of hypertension, dyslipidemia, diabetes, obesity, smoking, sedentarism, and hormonal contraception were similar in patients with or without aPL (p ≥ 0.253). Our study identified LA as an important marker for APS in pSS, particularly for stroke in young patients, warranting routine evaluation of these antibodies and rigorous intervention in modifiable risk factors.

Glucocorticoid: major factor for reduced immunogenicity of 2009 influenza A (H1N1) vaccine in patients with juvenile autoimmune rheumatic disease.

OBJECTIVE: To assess the immunogenicity and safety of non-adjuvanted influenza A H1N1/2009 vaccine in patients with juvenile autoimmune rheumatic disease (ARD) and healthy controls, because data are limited to the adult rheumatologic population. METHODS: A total of 237 patients with juvenile ARD [juvenile systemic lupus erythematosus (JSLE), juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM), juvenile scleroderma, and vasculitis] and 91 healthy controls were vaccinated. Serology for anti-H1N1 was performed by hemagglutination inhibition assay. Seroprotection rate, seroconversion rate, and factor-increase in geometric mean titer (GMT) were calculated. Adverse events were evaluated. RESULTS: Age was comparable in patients and controls (14.8 ± 3.0 vs 14.6 ± 3.7 years, respectively; p = 0.47). Three weeks after immunization, seroprotection rate (81.4% vs 95.6%; p = 0.0007), seroconversion rate (74.3 vs 95.6%; p < 0.0001), and the factor-increase in GMT (12.9 vs 20.3; p = 0.012) were significantly lower in patients with juvenile ARD versus controls. Subgroup analysis revealed reduced seroconversion rates in JSLE (p < 0.0001), JIA (p = 0.008), JDM (p = 0.025), and vasculitis (p = 0.017). Seroprotection (p < 0.0001) and GMT (p < 0.0001) were decreased only in JSLE. Glucocorticoid use and lymphopenia were associated with lower seroconversion rates (60.4 vs 82.9%; p = 0.0001; and 55.6 vs 77.2%; p = 0.012). Multivariate logistic regression including diseases, lymphopenia, glucocorticoid, and immunosuppressants demonstrated that only glucocorticoid use (p = 0.012) remained significant. CONCLUSION: This is the largest study to demonstrate a reduced but adequate immune response to H1N1 vaccine in patients with juvenile ARD. It identified current glucocorticoid use as the major factor for decreased antibody production. The short-term safety results support its routine recommendation for patients with juvenile ARD. ClinicalTrials.gov; NCT01151644.

Autoantibodies in patients with psoriatic arthritis on anti-TNFα therapy.

INTRODUCTION: Anti-TNFα therapy has been effective in the treatment of patients with refractory psoriatic arthritis (PSA). However, the risk of developing autoantibodies commonly found in rheumatic diseases in PSA patients undergoing this therapy is not clear. OBJECTIVE: To evaluate the induction of specific autoantibodies after anti-TNFα therapy in PSA patients. PATIENTS AND METHODS: Serum samples from 23 PSA patients (women: 61%, age: 45.04 ± 12.68 years, polyarticular: 69.6%, disease duration: 13.3 ± 7.7 years, infliximab: 82.60%) obtained immediately before (baseline) and approximately one year after the introduction of anti-TNF therapy (last sample) (385 ± 131.45 days), were analyzed. The analysis included detection of antinuclear antibodies (ANA) and anti-dsDNA antibodies (indirect immunofluorescence on Hep-2 cells and Crithidia luciliae, respectively); anti-RNP and anti-Sm (passive hemagglutination); and anti-Ro/ SS-A and/or anti-La/SS-B, anti-chromatin, anti-histones, anti-citrullinated peptide (CCP), and anti-cardiolipin (ELISA) antibodies. RESULTS: At baseline, ANA was positive in 47.8% of patients, with predominance of homogeneous nuclear pattern (81.8%). All baseline serum samples were negative for rheumatoid factor and antibodies to cardiolipin, RNP, Sm, Ro/SS-A, anti-La/SS-B, anti-histone, and anti-dsDNA antibodies, while two patients were positive for anti-chromatin and one for anti-CCP. All ANA-positive samples at baseline, except for one, remained positive after the introduction of anti-TNF therapy; however, de novo ANA reactivity was observed in four originally negative patients (33.3%). Anti-Ro/SS-A, La/SS-B, cardiolipin, histones, dsDNA, and rheumatoid factor antibodies remained negative in all final serum samples tested, and anti-chromatin positivity was detected in three other patients. CONCLUSION: Our findings have shown that anti-TNF therapy induced ANA positivity in one third of PSA patients. The concomitant use of methotrexate did not interfere with this finding. In addition, all serum samples were systematically negative for specific rheumatic autoantibodies tested after the introduction of the biological treatment.

Autoantibody profile in the experimental model of scleroderma induced by type V human collagen.

UNLABELLED: The aim of this study is to evaluate the humoral autoimmune response in the experimental model of systemic sclerosis (SSc) induced by human type V collagen (huCol V). New Zealand rabbits were immunized with huCol V in Freund's complete adjuvant (FCA) and boosted twice with 15 days intervals with huCol V in Freund's incomplete adjuvant. Control groups included animals injected only with FCA or bovine serum albumin. Bleeding was done at days 0, 30, 75 and 120. Tissue specimens were obtained for histopathological investigation. Serological analysis included detection of antibodies against huCol V and anti-topoisomerase I (Anti-Scl70) by enzyme-linked immunosorbent assay, antinuclear antibodies (ANA) by indirect immunofluorescence, and rheumatoid factor (RF) by a latex agglutination test. Target antigens were characterized by immunoblot. Histological analysis revealed extracellular matrix remodeling with fibrosis and vasculitis. Anti-Scl70 and ANA were detected as early as 30 days in all huCol V animals. The universal ANA staining pattern was Golgi-like. This serum reactivity was not abolished by previous absorption with huCol V. Characterization of the target antigen by immunoblot revealed two major protein fractions of 175,000 and 220,000 MW. Similarly to ANA, there was a gradual increase of reactivity throughout the immunization and also it was not abolished by preincubation of serum samples with huCol V. RF testing was negative in hyperimmune sera. CONCLUSION: The production of autoantibodies, including anti-Scl70, a serological marker for SSc associated with histopathological alterations, validates huCol V induced-experimental model and brings out its potential for understanding the pathophysiology of SSc.

Antineutrophil cytoplasmic antibodies in chronic rhinosinusitis may be a marker of undisclosed vasculitis.

BACKGROUND: Upper airway manifestations are common features of antineutrophil cytoplasmic antibody (ANCA)-related vasculitis. Determining the presence of this antibody in patients with chronic rhinosinusitis (CRS) may allow early identification and treatment of underlying vasculitis. Methods Forty-nine consecutive CRS patients and 165 age- and sex-matched healthy controls were evaluated for vasculitis complaints. ANCA were detected by indirect immunofluorescence, and antibodies to proteinase 3 (PR3) and myeloperoxidase were determined by ELISA. RESULTS: Patients and controls were comparable concerning the mean age (47.2 +/- 15 years versus 45 +/- 12.5 years; p = 0.303) and female predominance (73.5% versus 60%; p = 0.502). Vasculitis-associated complaints were reported in 8/49 (16.3%) patients: 7 patients reported a 10-year history of asthma and 1 patient had red/painful eyes associated with epistaxis. ANCA was positive in 5/49 (10%) patients and absent in controls (p < 0.0001). One patient had high titer cytoplasmic ANCA/PR3 and during the investigation developed clinical features of Wegener's granulomatosis. The other four patients had perinuclear ANCA, of whom three were asymptomatic and one is currently under surveillance for Churg-Strauss syndrome. Sinus computed tomography scan revealed that patients who were ANCA(+) had more extensive disease involvement than ANCA(-) patients (Lund-Mackay score median value, 21 versus 13; p = 0.008). CONCLUSION: ANCA may identify a subset of difficult to treat CRS patients with underlying vasculitis and may be useful for establishing an early diagnosis of vasculitis in CRS.

Endometriosis and systemic lupus erythematosus: a comparative evaluation of clinical manifestations and serological autoimmune phenomena.

PROBLEM: In view of evidences suggesting association between endometriosis (EM) and systemic lupus erythematosus (SLE), we have performed a comparative evaluation of clinical and humoral immunologic abnormalities in both diseases. METHOD OF STUDY: Forty-five women (18-40 years) with histologically confirmed pelvic EM, 21 healthy-women and 15 female SLE-patients (18-40 years) without surgically confirmed EM were prospectively evaluated. Immunologic investigations were performed by blinded researchers. RESULTS: None of the EM-patients fulfilled criteria for SLE. However, EM-patients presented higher frequencies of arthralgia (62%) and generalized myalgia (18%) superior than normal-controls (24%, P = 0.004/0%, P = 0.048) but comparable with SLE-patients (33%, P = 0.052/27%, P = 0.5). Similarly to SLE (7%), 9% of EM-patients presented fibromyalgia. Antinuclear antibodies (ANA) were detected in 18% of EM-sera, as compared with healthy-women (0%, P = 0.014) and SLE-patients (93%, P = 0.0005). In contrast with SLE, antibodies to dsDNA, Sm and U1RNP were negative in EM-sera. Anti-Ro and anticardiolipin antibodies were more often in SLE (40%, 33%) than in EM-patients (2%, P < 0.001/9%, P = 0.04). Elevated immune-complexes and low total complement were more frequent in SLE (40%, 13%) compared with EM-sera (7%, P = 0.005/0%, P = 0.01). CONCLUSIONS: Our data indicate differences of ANA antigenic specificity and complement consumption between EM and SLE. The high prevalence of generalized musculoskeletal complaints in EM justifies a multidisciplinary approach.

The clinical spectrum of antinuclear antibodies associated with the nuclear dense fine speckled immunofluorescence pattern.

OBJECTIVE: Autoantibodies to lens epithelium-derived growth factor (LEDGF) depict a distinctive nuclear dense fine speckled (DFS) pattern in the indirect immunofluorescence antinuclear antibody assay (IIF-ANA). Definition of the clinical spectrum associated with anti-LEDGF antibodies has been evolving over the last decade. We investigated the frequency, clinical spectrum, and immunologic specificity of the DFS pattern in a general clinical laboratory routine. METHODS. All serum samples entered for IIF-ANA determination within a 2 year period were examined for the DFS pattern. Positive samples with consistent clinical information were studied further by IIF with isotype-specific conjugate and immunoblot analysis. RESULTS: Among 13,641 ANA-positive samples, 5081 (37%) presented the DFS pattern. Within a 6 month nested period, there were 650 samples with DFS pattern, and consistent clinical data were available for 81 of these. DFS reactivity was mainly due to IgG. Most samples (86%) presented titer > or = 1/640. Eighty of the 81 DFS samples reacted with a 75 kDa band that comigrated with the band elicited by the standard anti-LEDGF serum. Antibodies that were affinity-purified from the 75 kDa band reproduced the DFS pattern on IIF-ANA. The clinical spectrum associated with DFS reactivity included autoimmune diseases (39%) and an array of nonautoimmune conditions (61%). Among the autoimmune patients, over half presented evidence of autoimmune thyroiditis. CONCLUSION: Anti-LEDGF/p75 antibodies are a common finding among ANA-positive individuals with no evidence of rheumatic autoimmune disease, and should be regarded as a low specificity finding even when in moderate or high titer.