The immunogenicity of seasonal and pandemic influenza vaccination in autoimmune inflammatory rheumatic patients-a 6-month follow-up prospective study.

INTRODUCTION: Influenza may cause severe complications in patients with autoimmune inflammatory rheumatic disease (AIRD), to whom vaccinations are especially recommended. However, AIRD patients require cautious scrutiny of immunogenicity as they might exhibit poor antibody response to vaccination, especially when taking immunomodulatory medications. AIM: The aim was to determine immunogenicity of seasonal and pandemic influenza vaccine in AIRD patients, its timeline/persistence, and influence of medications on immune response. METHODS: One hundred and thirty-seven AIRD and 54 healthy controls were vaccinated with trivalent seasonal influenza. After 3-5 weeks, 15 healthy controls and 93 AIRD were vaccinated with pandemic influenza vaccine, and 63 of patients were vaccinated a second time after 3-5 weeks. Sera were collected before vaccination, 18-90 days after each vaccination, and more than 180 days after the last vaccination. The immune response was measured using hemagglutination inhibition (HI) assay and IgG/IgA antibodies against influenza A/B with ELISA. RESULTS: Our findings indicate that following vaccination with seasonal influenza vaccine, seroprotection, seroresponse, and change in geometric mean titers (GMT) in AIRD patients was not compromised compared to healthy. Similarly, we report for pandemic influenza vaccination little added benefit of the second dose. We confirm lowest increase in HI titer in rituximab-treated AIRD compared to other medications. Vaccination largely tilts the balance from negative ELISA A IgG and IgA titers to positive titers in seasonal H1N1 seroresponsive AIRD patients and controls. A significant decrease in HI GMT and seroprotection was observed only in AIRD at > 180 days after vaccination highlighting an absent persistence of immunogenic response in AIRD patients. Due to high initial HI titers for influenza vaccine, we foresee their benefit in personalized medicine in the future. CONCLUSION: Influenza vaccination is immunologically active for AIRD, with little value of the second dose of the pandemic vaccine and further scrutiny on persistence of immune response to vaccine in AIRD is needed.

Insight into inflammatory cell and cytokine profiles in adult IgA vasculitis.

Immunoglobulin A vasculitis (IgAV) is an immune complex, small vessel vasculitis with dominant IgA deposits in vessel walls, predominantly affecting the pediatric population. However, adults frequently have more severe gastrointestinal tract (GIT) and renal involvements as compared to children. Our aim was to study serological and cellular biomarkers to support clinicians in their diagnosis and the course of IgAV in adult patients. This cross-sectional study included 62 adult IgAV patients and 53 healthy blood donors (HBDs). Demographic and clinical data, as well as routine laboratory tests, were meticulously analyzed. Serum levels of IL-1ß, IL-2, IL-6, IL-8, IL-9, IL-10, IL-17A, IL-23, TNF-α and serum amyloid A (SAA) were measured. Percentages of neutrophils, lymphocytes, and monocytes with neutrophil expression of L-selectin and integrin αM were determined by flow cytometry. SAA (12-fold), IL-6 (3-fold), IL-8 (2-fold), and TNF-α (2-fold) were significantly elevated in sera of adult IgAV patients compared to HBDs. There was a 16% elevation in neutrophils in IgAV patients, with IgAV neutrophils showing significantly higher CD62L surface expression. IgAV patients with GIT involvement exhibited elevated numbers of leukocytes, neutrophils, and neutrophil/lymphocyte (NLR), but lower neutrophil CD11b expression, as compared to IgAV patients without GIT. IgAV patients exhibit a low-medium grade inflammatory, neutrophil-driven response. Patients with GIT can be distinguished by their elevated NLR.

Autoantibodies against dsDNA measured with nonradioactive Farr assay-an alternative for routine laboratories.

Autoantibodies against dsDNA are utilized for the diagnosis and prognosis of SLE as they are highly specific and correlate with disease activity/renal involvement. However, different detection methods are used in routine diagnostic laboratories. Farr radioimmunoassay (Farr-RIA) has been designated as the preferred method, since it provides very specific and at the same time quantitative results, enabling follow-up of level variations over time. Using intercalating fluorescent dsDNA dye would enable all the benefits of Farr-RIA without the radioactive material and organic solvents. To develop a modified fluorescent Farr method (Farr-FIA) and compare it to the classical Farr-RIA in regard to laboratory parameters, as well as clinical utility. Assays were tested on sera of 70 SLE patients, 78 other autoimmune patients, and 145 healthy blood donors. DNA for Farr-FIA was isolated from healthy donor, for Farr-RIA, 14C-labeled dsDNA from E. coli was used and mixed with sera in borate-buffered saline, followed by precipitation with saturated ammonium sulfate solution and centrifugation. The supernatant (S) was separated from the precipitate (P), and content of dsDNA was measured with PicoGreen (Invitrogen) in Farr-FIA or radioactive isotope in scintillation solution in Farr-RIA. The results were calculated as a ratio (P-S)/(P+S). Farr-FIA has a diagnostic sensitivity of 53% and diagnostic specificity of 100% (ROC AUC 0.781). Good correlation and agreement were shown between Farr-RIA and Farr-FIA. Also, there is good correlation between Farr-FIA and SLEDAI, comparable to that of Farr-RIA. Farr-FIA differs from Farr-RIA in the changed detection system yielding comparable results and thus could represent a nonradioactive replacement for Farr-RIA.

Analysis of Drug Effects on Primary Human Coronary Artery Endothelial Cells Activated by Serum Amyloid A.

BACKGROUND: RA patients have a higher incidence of cardiovascular diseases compared to the general population. Serum amyloid A (SAA) is an acute-phase protein, upregulated in sera of RA patients. AIM: To determine the effects of medications on SAA-stimulated human coronary artery endothelial cells (HCAEC). METHODS: HCAEC were preincubated for 2 h with medications from sterile ampules (dexamethasone, methotrexate, certolizumab pegol, and etanercept), dissolved in medium (captopril) or DMSO (etoricoxib, rosiglitazone, meloxicam, fluvastatin, and diclofenac). Human recombinant apo-SAA was used to stimulate HCAEC at a final 1000 nM concentration for 24 hours. IL-6, IL-8, sVCAM-1, and PAI-1 were measured by ELISA. The number of viable cells was determined colorimetrically. RESULTS: SAA-stimulated levels of released IL-6, IL-8, and sVCAM-1 from HCAEC were significantly attenuated by methotrexate, fluvastatin, and etoricoxib. Both certolizumab pegol and etanercept significantly decreased PAI-1 by an average of 43%. Rosiglitazone significantly inhibited sVCAM-1 by 58%. CONCLUSION: We observed marked influence of fluvastatin on lowering cytokine production in SAA-activated HCAEC. Methotrexate showed strong beneficial effects for lowering released Il-6, IL-8, and sVCAM-1. Interesting duality was observed for NSAIDs, with meloxicam exhibiting opposite-trend effects from diclofenac and etoricoxib. This represents unique insight into specific responsiveness of inflammatory-driven HCAEC relevant to atherosclerosis.

Evaluating the utility of autoantibodies for disease activity and relapse in giant cell arteritis.

In patients with giant cell arteritis (GCA), autoantibodies against cytoskeletal elements, cardiolipin, neutrophil cytoplasmic antigens, ferritin, endothelial and smooth muscle cells have been reported, however no updated reviews are available evaluating their clinical utility. Methodology of detection is important, especially for quantitative assays, e.g. enzyme-linked immunoassays and multiplex beadbased immunoassays, while semiquantitative assays contribute valuable data on isoforms, epitope mapping and cellular localization. Most studies to date reporting on antiphospholipid antibodies in GCA have focused on anti-cardiolipin antibodies (aCL), while the highest prevalence of autoantibodies in GCA patients was reported for the anti-N-terminal peptides of the ferritin heavy chain (92%). Antineutrophil cytoplasmic antibodies were shown to be present in only a small percentage of GCA patients, decreasing after therapy, however in combination with aCL and antibodies against peptides of N-terminal ferritin heavy chain, they could represent an added value in detecting relapse in GCA patients.

A concise review of significantly modified serological biomarkers in giant cell arteritis, as detected by different methods.

Giant cell arteritis (GCA) is a primary systemic vasculitis present in subjects older than 50years with involvement of large- and medium-sized arteries. Early diagnosis for GCA is essential to prevent serious complications, such as permanent vision loss and/or cerebrovascular events. Elevated inflammatory cytokines, with acute phase and other proteins dominate large- and medium-sized arteries leading to stenosis or occlusion of arterial lumen. To date, there are no reliable serological markers for monitoring GCA. The review aims to provide concise overview of published GCA studies in order to: a) identify significantly changed serological biomarkers in GCA and compare the influences of techniques for marker evaluation and b) investigate most promising markers in GCA using analyte frequency and meta-analysis.

A study of extracellular vesicle concentration in active diabetic Charcot neuroarthropathy.

It was the aim of this work to determine whether the plasma concentration of extracellular vesicles (EVs) in active diabetic Charcot neuroarthropathy (CN) is connected to the inflammatory markers, temperature elevation in the affected foot and concentration of soluble receptor for advanced glycation end products (RAGE). EVs were isolated from peripheral blood of 35 patients with active CN. EVs were counted after repetitive centrifugation and washing of samples, by flow cytometry. Foot temperature was measured by infrared thermometer. Concentration of soluble receptor for advanced glycation end products (RAGE) was determined by enzyme-linked immunosorbent assay (ELISA). We found statistically significant correlations of EV concentration (but not soluble RAGE concentration) with C-Reactive Protein (CRP) and with temperature difference between the affected and the contralateral foot (r=0.40, p=0.032; r=0.89, p<10-8, respectively). We provide evidence that the concentration of EVs is related to elevation of markers of inflammation (CRP and foot temperature difference) in acute Diabetic CN. EV-based markers could be considered as a potential aid in early diagnosis of CN.

Risk of peripartum hysterectomy by mode of delivery and prior obstetric history: data from a population-based study.

PURPOSE: To provide an estimate of the incidence of peripartum hysterectomy in the state of New Jersey and calculate the effect of mode of delivery and prior obstetric history. METHODS: A perinatal-linked dataset provided by the Maternal Child Health Epidemiology Program in the New Jersey Department of Health was used to obtain information from birth certificates and hospital discharge records. Using multivariate logistic regression, various demographic and clinical factors were assessed for association with peripartum hysterectomy. RESULTS: A total of 1,004,116 births were identified between 1997 and 2005 and 853 peripartum hysterectomies were performed (0.85/1,000 deliveries). Parity increased the risk of hysterectomy with nulliparous women having approximately half the risk compared to multiparous women. Cesarean delivery with no previous c-section almost doubled the risk (OR 2.20, CI 1.80-26.69) while in the presence of a previous c-section the risk was almost four times higher (OR 4.51, CI 3.76-5.40). Operative vaginal delivery did not result in any increase in the risk. CONCLUSIONS: Mode of delivery and prior obstetric history are major risk factors for peripartum hysterectomy. Patients desiring cesarean delivery need to be counseled on the risk of this serious complication.

Impact of mode of delivery on neonatal complications: trends between 1997 and 2005.

OBJECTIVE: This study examined whether rates of selected neonatal complications vary by mode of delivery and whether these rates are changing as a result of the increasing cesarean delivery rate. METHOD: Birth certificates in New Jersey from 1997 to 2005 were matched to hospital discharge records for mothers and newborns. RESULTS: In New Jersey, the total cesarean section rate for 2005 was 35.3%, a relative increase of 46% since 1997 (from 24.2%). Rates of transient tachypnea of the newborn (TTN) and respiratory distress syndrome (RDS), regardless of mode of delivery, increased between 1997 and 2005 from 3.3 to 3.9% and 2.1 to 2.4%, respectively. Newborn injuries declined sharply (from 4.1 to 2.6%), whereas intra-ventricular hemorrhage (IVH) rates remained stable. The rates of RDS, TTN and IVH were highest for cesarean delivery without trial of labor, while the rate of injuries was highest for instrumental vaginal delivery. CONCLUSION: Neonatal complication rates varied by mode of delivery and decreased with gestational age.

Disparities in asthma hospitalizations among children seen in the emergency department.

We examined the race/ethnicity variation in the risk of hospitalization among children seen in the emergency department (ED) for asthma. ED and hospitalization records for children 1 to 19 years of age in New Jersey for 2004 and 2005 were linked. The dataset identified 47,548 ED and hospitalizations among 37,216 children. ED and hospitalization rates indicated persistent disparities in pediatric asthma. ED admission rates were similar across race/ethnic groups, suggesting similar management of pediatric asthma patients once they are seen in the ED. Integrating existing ED and hospitalization records will enhance asthma surveillance and the targeting of interventions to reduce race/ethnicity disparities.

Maternal obesity: can pregnancy weight gain modify risk of selected adverse pregnancy outcomes?

Reports by the Institute of Medicine (IOM) recommend that gestational weight gain goals should be modified according to prepregnancy body mass index (BMI), which could result in better maternal and infant outcomes. The authors assessed whether the risk of the pregnancy outcomes such as rate of cesarean section to primiparous and multiparous women, macrosomia, and breastfeeding at 10 weeks postpartum can be modified by following the IOM guidelines for gestational weight gain irrespective of prepregnancy BMI. Staff from the New Jersey Pregnancy Risk Assessment Monitoring System interviewed a sample of women who delivered live births in New Jersey during 2002 through 2005 (n = 7661). In New Jersey, 18% of mothers were obese, 13% were overweight, and 16% were underweight. In logistic regression analyses, after controlling for maternal characteristics, the effect of prepregnancy obesity and weight gain more than 34 lb independently and significantly increased the risk of all four adverse outcomes. For no outcomes was the 25- to 34-pound weight gain category significantly distinguishable from the 16- to 24-pound reference category. These results strongly support the idea that the IOM weight gain recommendation (education during preconception regarding the importance of optimal BMI at the start of pregnancy) will help to achieve better pregnancy outcomes in obese and overweight women.

Surveillance of cesarean section deliveries, New Jersey, 1999-2004.

BACKGROUND: Nationally and in New Jersey, the cesarean delivery rate has been increasing steadily for nearly a decade, and especially since 1999. The purpose of this study was to describe recent trends in cesarean section delivery in New Jersey. METHODS: Data on delivery method, medical indications and patient characteristics were extracted from electronic birth certificate files. RESULTS: Cesarean section deliveries increased as a proportion of live births by 6 percent annually. Growth was roughly uniform across Robson's clinical classification. Repeat cesareans contributed only proportionately to the overall trend. The greatest acceleration was observed for procedures without trial of labor, and in medical situations where cesarean delivery had been relatively rare. CONCLUSIONS: Medical indications recorded on the birth certificate explained little of the rapid growth in utilization of cesarean delivery, since trends were comparable in most categories we examined. A sustained autonomous shift in practice patterns, patient preferences, or both seems the most likely driver of the overall trend.

Pediatric hospitalizations for asthma: use of a linked file to separate person-level risk and readmission.

INTRODUCTION: Disparities in asthma hospitalization by gender, age, and race/ethnicity are thought to be driven by a combination of 2 factors: disease severity and inadequate health care. Hospitalization data that fail to differentiate between numbers of admissions and numbers of individuals limit the ability to derive accurate conclusions about disparities and risks. METHODS: Hospitalization records for pediatric asthma patients (aged one to 14 years) were extracted from New Jersey Hospital Discharge Files (for the years 1994 through 2000) and then linked by patient identifiers using a probabilistic matching algorithm. The analysis file contained 30,400 hospital admissions for 21,016 children. Hospitalization statistics were decomposed into persons hospitalized and number of hospitalizations. Analysis of readmission within 180 days of discharge used additional records from 2001 to avoid bias due to truncated observation. RESULTS: Overall, 22.9% of children in our analysis had repeat asthma admissions within the same age interval, accounting for 30.9% of all hospitalizations. Also among all children, 11.7% had at least one readmission within 180 days of a prior discharge. The risk of hospitalization was higher for boys, decreased by age for both genders, was lowest for white children and highest for black children. Readmission rates were higher for black and Hispanic girls than boys in older age groups, but were otherwise relatively uniform by gender and age. CONCLUSION: Decomposition of ratios of total hospitalizations to population illuminates components of risk and suggests specific causes of disparity.