Long-term outcomes of childhood-onset systemic lupus erythematosus.

OBJECTIVE: Data on the long-term outcome of patients with childhood-onset Systemic Lupus Erythematosus (cSLE) are scarce. Aims of this study were to describe the long-term outcomes of cSLE and to identify factors associated with the development of damage and persistent disease activity. METHODS: We conducted a retrospective multicentre study using data from the PEDIALUP registry of the Juvenile Inflammatory Rheumatism (JIR) cohort database. Demographic characteristics, clinical manifestations, laboratory, radiological, histological and treatment data were collected from medical records during follow-up. RESULTS: A total of 138 patients with cSLE, diagnosed between 1971 and 2015, were included. With a median follow-up of 15.4 [9.6-22.4] years, 51% of patients had a SLICC-Damage Index score ≥ 1 at last follow-up with the musculoskeletal, cutaneous, renal, neurological, and cardiovascular damage being the most common manifestations. The proportion of patients with a SLICC-DI score ≥ 1 increased significantly with the duration of the follow-up (p< 0.001). On multivariate analysis, duration of follow-up was associated with increased risk of cumulative damage (OR 1.08, 95% CI 1.01, 1.15, p= 0.035). At the last visit, 34% of patients still had active disease with a SLEDAI score of ≥ 6. On multivariate analysis, Sub-Saharan African ethnicity was associated with 7-fold increased odds of having active disease at the last visit compared with Caucasians (OR 7.44, 95% CI 2.24, 24.74, p= 0.0002). CONCLUSION: The prevalence of damage remains high in patients with cSLE even when the diagnosis of c-SLE has been made in the recent decades.

Short-chain fatty acids inhibit the activation of T lymphocytes and myeloid cells and induce innate immune tolerance.

The intestinal microbiota contributes to gut immune homeostasis, where short-chain fatty acids (SCFAs) function as the major mediators. We aimed to elucidate the immunomodulatory effects of acetate, propionate, and butyrate. With that in mind, we sought to characterise the expression of SCFA receptors and transporters as well as SCFAs' impact on the activation of different immune cells. Whereas all three SCFAs decreased tumour necrosis factor (TNF)-α production in activated T cells, only butyrate and propionate inhibited interferon (IFN)-γ, interleukin (IL)-17, IL-13, and IL-10 production. Butyrate and propionate inhibited the expression of the chemokine receptors CCR9 and CCR10 in activated T- and B-cells, respectively. Similarly, butyrate and propionate were effective inhibitors of IL-1ß, IL-6, TNF-α, and IL-10 production in myeloid cells upon lipopolysaccharide and R848 stimulation. Acetate was less efficient at inhibiting cytokine production except for IFN-α. Moreover, SCFAs inhibited the production of IL-6 and TNF-α in monocytes, myeloid dendritic cells (mDC), and plasmacytoid dendritic cells (pDC), whereas acetate effects were relatively more prominent in pDCs. In monocytes and mDCs, acetate was a less efficient inhibitor, but it was equally effective in inhibiting pDCs activation. We also studied the ability of SCFAs to induce trained immunity or tolerance. Butyrate and propionate - but not acetate - prevented Toll-like receptor-mediated activation in SCFA-trained cells, as demonstrated by a reduced production of IL-6 and TNF-α. Our findings indicate that butyrate and propionate are equally efficient in inhibiting the adaptive and innate immune response and did not induce trained immunity. The findings may be explained by differential SCFA receptor and transporter expression profiles of the immune cells.

Preoperative platelet transfusions to reverse antiplatelet therapy for urgent non-cardiac surgery: an observational cohort study.

Essentials An increasing number of patients requiring surgery receive antiplatelet therapy (APT). We analyzed 181 patients receiving presurgery platelet transfusions to reverse APT. No coronary thrombosis occurred after platelet transfusion. This justifies a prospective trial to test preoperative platelet transfusions to reverse APT. SUMMARY: Background Patients receiving antiplatelet therapy (APT) have an increased risk of perioperative bleeding and cardiac adverse events (CAE). Preoperative platelet transfusions may reduce the bleeding risk but may also increase the risk of CAE, particularly coronary thrombosis in patients after recent stent implantation. Objectives To analyze the incidence of perioperative CAE and bleeding in patients undergoing non-cardiac surgery using a standardized management of transfusing two platelet concentrates preoperatively and restart of APT within 24-72 h after surgery. Methods A cohort of consecutive patients on APT treated with two platelet concentrates before non-cardiac surgery between January 2012 and December 2014 was retrospectively identified. Patients were stratified by the risk of major adverse cardiac and cerebrovascular events (MACCE). The primary objective was the incidence of CAE (myocardial infarction, acute heart failure and cardiac troponine T increase). Secondary objectives were incidences of other thromboembolic events, bleedings, transfusions and mortality. Results Among 181 patients, 88 received aspirin, 21 clopidogrel and 72 dual APT. MACCE risk was high in 63, moderate in 103 and low in 15 patients; 67 had cardiac stents. Ten patients (5.5%; 95% CI, 3.0-9.9%) developed a CAE (three myocardial infarctions, four cardiac failures and three troponin T increases). None was caused by coronary thrombosis. Surgery-related bleeding occurred in 22 patients (12.2%; 95% CI, 8.2-17.7%), making 12 re-interventions necessary (6.6%; 95% CI, 3.8-11.2%). Conclusion Preoperative platelet transfusions and early restart of APT allowed urgent surgery and did not cause coronary thromboses, but non-thrombotic CAEs and re-bleeding occurred. Randomized trials are warranted to test platelet transfusion against other management strategies.

Immunoglobulin (Ig)M antibodies to proteinase 3 in granulomatosis with polyangiitis and microscopic polyangiitis.

Anti-neutrophil cytoplasmic antibodies (ANCA) appear to play an important role in the pathogenesis of ANCA-associated vasculitis (AAV). However, ANCA alone are not sufficient to generate disease, and some evidence suggests that infectious triggers may serve as inciting events for AAV disease activity. Antibodies of the immunoglobulin (Ig)M isotype often serve as markers of recent infection, and IgM ANCA have been identified previously in patients with AAV, although the frequency and clinical relevance of IgM ANCA is not well established. We sought to characterize IgM ANCA more clearly by creating a novel enzyme-linked immunosorbent assay (ELISA) for IgM antibodies to proteinase 3 [IgM proteinase 3 (PR3)-ANCA], which we applied to two large, clinically well-characterized trial cohorts of patients with granulomatosis with polyangiitis and microscopic polyangiitis. In the first cohort, IgM PR3-ANCA occurred with a frequency of 15·0%, and were associated with a higher degree of disease severity and a trend towards a higher rate of alveolar haemorrhage (29·6 versus 15·7%, P = 0·10). Analysis of follow-up samples in this cohort showed that the presence of IgM PR3-ANCA was transient, but could recur. In the second cohort, IgM PR3-ANCA occurred with a frequency of 41·1%, and were also associated with a higher degree of disease severity. A higher rate of alveolar haemorrhage was observed among those with IgM PR3-ANCA (45·3 versus 15·8%; P < 0·001). The association of transient IgM PR3-ANCA with an acute respiratory manifestation of AAV suggests a possible link between an infectious trigger and AAV disease activity.

[From myxomas of the skin to LVAD implantation : A 28-year-old female patient with Carney complex]. / Von Hautmyxomen zur LVAD-Implantation : Eine 28-jährige Patientin mit Carney-Komplex.

Multiple skin lesions, endocrine dysfunction and cardiac myxomas are characteristic symptoms of Carney complex. This case report gives an overview about the major and minor criteria of Carney complex and presents the course of a female patient who developed severe cardiac insufficiency with multiple organ failure because of recurring heart operations leading to implantation of a left ventricular assist device (LVAD).

[Prevention of infections in adults and adolescents with systemic lupus erythematosus: Guidelines for the clinical practice based on the literature and expert opinion]. / Prévention des infections au cours du lupus systémique chez l'adulte et l'adolescent : élaboration de recommandations pour la pratique clinique, à partir d'une analyse de la littérature et de l'avis d'experts.

PURPOSE: To develop French recommendations about the management of vaccinations, the screening of cervical cancer and the prevention of pneumocystis pneumonia in systemic lupus erythematosus (SLE). METHODS: Thirty-seven experts qualified in internal medicine, rheumatology, dermatology, nephrology and pediatrics have selected recommendations from a list of proposition based on available data from the literature. For each recommendation, the level of evidence and the level of agreement among the experts were specified. RESULTS: Inactivated vaccines do not cause significant harm in SLE patients. Experts recommend that lupus patient should receive vaccinations accordingly to the recommendations and the schedules for the general public. Pneumococcal vaccination is recommended for all SLE patients. Influenza vaccination is recommended for immunosuppressed SLE patients. Live attenuated vaccines should be avoided in immunosuppressed patients. Yet, recent works suggest that they can be considered in mildly immunosuppressed patients. Experts have recommended a cervical cytology every year for immunosuppressed patients. No consensus was obtained for the prevention of pneumocystis pneumonia. CONCLUSION: These recommendations can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of SLE patients.

Role of Experience, Leadership and Individual Protection in the Cath Lab--A Multicenter Questionnaire and Workshop on Radiation Safety.

PURPOSE: Radiation exposure in invasive cardiology remains considerable. We evaluated the acceptance of radiation protective devices and the role of operator experience, team leadership, and technical equipment in radiation safety efforts in the clinical routine. MATERIALS AND METHODS: Cardiologists (115 from 27 centers) answered a questionnaire and documented radiation parameters for 10 coronary angiographies (CA), before and 3.1 months after a 90-min. mini-course in radiation-reducing techniques. RESULTS: Mini-course participants achieved significant median decreases in patient dose area products (DAP: from 26.6 to 13.0 Gy × cm(2)), number of radiographic frames (-29%) and runs (-8%), radiographic DAP/frame (-2%), fluoroscopic DAP/s (-39%), and fluoroscopy time (-16%). Multilevel analysis revealed lower DAPs with decreasing body mass index (-1.4 Gy × cm(2) per kg/m(2)), age (-1.2 Gy × cm(2)/decade), female sex (-5.9 Gy × cm(2)), participation of the team leader (-9.4 Gy × cm(2)), the mini-course itself (-16.1 Gy × cm(2)), experience (-0.7 Gy × cm(2)/1000 CAs throughout the interventionalist's professional life), and use of older catheterization systems (-6.6 Gy × cm(2)). Lead protection included apron (100%), glass sheet (95%), lengthwise (94%) and crosswise (69%) undercouch sheet, collar (89%), glasses (28%), cover around the patients' thighs (19%), foot switch shield (7%), gloves (3%), and cap (1%). CONCLUSION: Radiation-protection devices are employed less than optimally in the clinical routine. Cardiologists with a great variety of interventional experience profited from our radiation safety workshop - to an even greater extent if the interventional team leader also participated. KEY POINTS: Radiation protection devices are employed less than optimally in invasive cardiology. The presented radiation-safety mini-course was highly efficient. Cardiologists at all levels of experience profited from the mini-course - considerably more so if the team leader also took part. Interventional experience was less relevant for radiation reduction. Consequently both fellows and trainers should be encouraged to practice autonomy in radiation safety.

Kidney transplantation process in Brazil represented in business process modeling notation.

Kidney transplantation is considered to be the best treatment for people with chronic kidney failure, because it improves the patients' quality of life and increases their length of survival compared with patients undergoing dialysis. The kidney transplantation process in Brazil is defined through laws, decrees, ordinances, and resolutions, but there is no visual representation of this process. The aim of this study was to analyze official documents to construct a representation of the kidney transplantation process in Brazil with the use of business process modeling notation (BPMN). The methodology for this study was based on an exploratory observational study, document analysis, and construction of process diagrams with the use of BPMN. Two rounds of validations by specialists were conducted. The result includes the kidney transplantation process in Brazil representation with the use of BPMN. We analyzed 2 digital documents that resulted in 2 processes with 45 total of activities and events, 6 organizations involved, and 6 different stages of the process. The constructed representation makes it easier to understand the rules for the business of kidney transplantation and can be used by the health care professionals involved in the various activities within this process. Construction of a representation with language appropriate for the Brazilian lay public is underway.

ECG-gated coronary angiography enables submillisievert imaging in invasive cardiology.

BACKGROUND: The median dose area products (DAP) and effective doses (ED) of patients arising from coronary angiography (CA) are considerable: According the 2013 National German Registry, they amount to 19.8 Gy × cm(2) and 4.0 mSv, respectively. METHODS: We investigated the feasibility of prospective electrocardiogram (ECG)-gated coronary angiography (CA)-a novel technique in invasive cardiology-with respect to possible reduction in irradiation effects. Instead of universally fix-rated radiographic acquisition within 7.5-15 frames/s, one single frame/heartbeat was triggered toward the diastolic moment immediately before atrial contraction (77 % of ECG-RR interval) most likely to provide motion-free and hence optimized resolution of the coronary tree. For 200 patients (body mass index 27.8 kg/m(2), age 67.5 years, male 55 %, 68 bpm) undergoing ECG-gated CA, we measured various median (interquartile range) parameters for radiation exposure. RESULTS: The total DAP was 0.64 (0.46-1.00), radiographic fraction was 0.30 (0.19-0.43), and fluoroscopic fraction was 0.35 (0.21-0.57) Gy × cm(2). Radiographic imaging occurred within 21.7 s (17.1-26.3), with 25 frames (20-30) over the course of 7 runs (6-8). Fluoroscopy time was 119 s (94-141). Radiographic DAP was 12.6 mGy × cm(2)/frame and 13.8 mGy × cm(2)/s. Fluoroscopic DAP was 0.8 mGy × cm(2)/pulse and 3.1 mGy × cm(2)/s. Patient reference point air kerma was 17.0 mGy (11.1-28.1) and contrast volume was 70 ml (60-85). CONCLUSION: In conclusion, invasive ECG-gated coronary imaging is feasible in clinical routine and enables patient EDs of approx. 3 % of typical values in invasive cardiology: 0.13 mSv (0.09-0.20).

[Screening and management of cardiovascular risk factors in systemic lupus erythematosus: Recommendations for clinical practice based on the literature and expert opinion]. / Dépistage et prise en charge du risque cardiovasculaire au cours du lupus systémique : élaboration de recommandations pour la pratique clinique, à partir d'une analyse de la littérature et de l'avis d'experts.

PURPOSE: To develop French recommendations about screening and management of cardiovascular risk factors in systemic lupus erythematosus (SLE). METHODS: Thirty-nine experts qualified in internal medicine, rheumatology and nephrology have selected recommendations from a list developed based on evidence from the literature. For each recommendation, the level of evidence and the level of agreement among the experts were specified. RESULTS: Experts recommended an annual screening of cardiovascular risk factors in SLE. Statins should be prescribed for primary prevention in SLE patients based on the level of LDL-cholesterol and the number of cardiovascular risk factors, considering SLE as an additional risk factor. For secondary prevention, experts have agreed on an LDL-cholesterol target of <0.7 g/L. Hypertension should be managed according to the 2013 European guidelines, using renin-angiotensin system blockers as first line agents in case of renal involvement. Aspirin can be prescribed in patients with high cardiovascular risk or with antiphospholipid antibodies. CONCLUSION: These recommendations about the screening and management of cardiovascular risk factors in SLE can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of SLE patients.

Latest-generation catheterization systems enable invasive submillisievert coronary angiography.

BACKGROUND: The radiation risk of patients undergoing invasive cardiology remains considerable and includes skin injuries and cancer. To date, submillisievert coronary angiography has not been considered feasible. PATIENTS AND METHODS: In 2011, we compared results from 100 consecutive patients undergoing elective coronary angiography using the latest-generation flat-panel angiography system (FPS) with results from examinations by the same operator using 106 historic controls with a conventional image-intensifier system (IIS) that was new in 2002. RESULTS: The median patient exposure parameters were measured as follows: dose-area product (DAP) associated with radiographic cine acquisitions (DAP(R)) and fluoroscopy (DAP(F)) scenes, radiographic frames and runs, and cumulative exposure times for radiography and fluoroscopy. On the FPS as compared to the traditional IIS, radiographic detector entrance dose levels were reduced from 164 to 80 nGy/frame and pulse rates were lowered from 12.5/s to 7.5/s during radiography and from 25/s to 4/s during fluoroscopy. The cardiologist's performance patterns remained comparable over the years: fluoroscopy time was constant and radiography time even slightly increased. Overall patient DAP decreased from 7.0 to 2.4 Gy × cm(2); DAP(R), from 4.2 to 1.7 Gy × cm(2); and DAP(F), from 2.8 to 0.6 Gy × cm(2). Time-adjusted DAP(R)/s decreased from 436 to 130 mGy × cm(2) and DAP(F)/s, from 21.6 to 4.4 mGy × cm(2). Cumulative patient skin dose with the FPS amounted to 67 mGy, and the median (interquartile range) of effective dose was 0.5 (0.3 … 0.7) mSv. CONCLUSION: Consistent application of radiation-reducing techniques with the latest-generation flat-panel systems enables submillisievert coronary angiography in invasive cardiology.

[Diagnosis of systolic and diastolic heart failure]. / Diagnostik der systolischen und diastolischen Herzinsuffizienz.

In this review, heart failure is confined to etiologies not due to rhythm disturbances or valvular heart disease. Besides measurement of natriuretic peptides, echocardiography is established as an important diagnostic procedure. Echocardiography is especially helpful in discriminating between heart failure with preserved ejection fraction (HF-PEF) and reduced ejection fraction (HF-REF). Because of its ease to be performed, the 6 min walk test continues to be a standard diagnostic procedure. Cardiopulmonary exercise testing provides more detailed information regarding differential diagnostic and prognostic considerations.

Long-term efficacy of a mini-course in radiation-reducing techniques in invasive cardiology.

PURPOSE: To validate the long-term efficacy of a 90-min. educational mini-course in less-irradiating cardiac interventional techniques. MATERIALS AND METHODS: Before, two months after, and two years after the mini-course (periods I, II, and III), we analyzed the following radiation dose parameters for ten coronary angiographies (CA), performed by each of 7 cardiologists: total dose-area product (DAP), radiographic and fluoroscopic DAP fractions, number of radiographic frames and runs, and fluoroscopy time. RESULTS: The median patient DAP for periods I, II and III was 31.4, 15.8 and 8.5 Gy × cm2, respectively. The long-term effect was related to shorter median fluoroscopy times (180, 172, and 120 s), shorter (57, 52, and 45) and fewer (12, 12, and 10) radiographic runs, consistent collimation and restriction to an adequate image quality. Both radiographic DAP/frame (28.7, 17.0, and 18.4 mGy × cm2) and fluoroscopic DAP/second (45.7, 24.2, and 10.0 mGy × cm2) decreased significantly. The multivariate linear regression analysis confirmed the increasing efficacy of the mini-course itself (-44.6 and -60.7%), and revealed a decreasing influence of the interventionalist's experience (-8.6% and -4.9% per 1,000 CAs, lifelong performed until the mini-course). The number of CAs performed after the mini-course did not influence the long-term DAP results. CONCLUSION: The presented educational mini-course allows a significant, long-lasting, and apparently ongoing reduction of patient radiation exposure due to CA. A self-surveillant documentation of relevant radiation parameters is well suited to monitor and improve each operator's individual long-term radiation-reducing efforts.

Treatment of acute decompensation of maple syrup urine disease in adult patients with a new parenteral amino-acid mixture.

BACKGROUND: Acute decompensation of maple syrup urine disease (MSUD) is usually treated by enteral feeding with an amino-acid mixture without leucine (Leu), valine or isoleucine. However, its administration is ineffective in cases of gastric intolerance and some adult patients refuse enteral feeding via a nasogastric tube. We developed a new parenteral amino-acid mixture for patients with MSUD. METHODS: Seventeen decompensation episodes in four adult patients with MSUD treated with a parenteral amino-acid mixture (group P) were compared to 18 previous episodes in the same patients treated by enteral feeding (group E). RESULTS: The mean Leu concentration at presentation was similar in the groups P and E (1196.9 µmol/L and 1212.2 µmol/L, respectively). The mean decrease in the Leu concentration during the first 3 days of hospitalisation was significantly higher in group P than group E (p = 0.0026); there were no side effects. The mean duration of hospitalisation was similar (4 vs. 4.5 days, p = NS). No patient in group P deteriorated whereas one patient in group E required dialysis. CONCLUSION: This new parenteral amino-acid mixture is safe and allows efficient Leu concentration decrease during acute MSUD decompensation episodes in adults. Its use avoids the need for nasogastric tube insertion.

Application of the intelligent techniques in transplantation databases: a review of articles published in 2009 and 2010.

The replacement of defective organs with healthy ones is an old problem, but only a few years ago was this issue put into practice. Improvements in the whole transplantation process have been increasingly important in clinical practice. In this context are clinical decision support systems (CDSSs), which have reflected a significant amount of work to use mathematical and intelligent techniques. The aim of this article was to present consideration of intelligent techniques used in recent years (2009 and 2010) to analyze organ transplant databases. To this end, we performed a search of the PubMed and Institute for Scientific Information (ISI) Web of Knowledge databases to find articles published in 2009 and 2010 about intelligent techniques applied to transplantation databases. Among 69 retrieved articles, we chose according to inclusion and exclusion criteria. The main techniques were: Artificial Neural Networks (ANN), Logistic Regression (LR), Decision Trees (DT), Markov Models (MM), and Bayesian Networks (BN). Most articles used ANN. Some publications described comparisons between techniques or the use of various techniques together. The use of intelligent techniques to extract knowledge from databases of healthcare is increasingly common. Although authors preferred to use ANN, statistical techniques were equally effective for this enterprise.

Artificial intelligence techniques: predicting necessity for biopsy in renal transplant recipients suspected of acute cellular rejection or nephrotoxicity.

The gold standard for nephrotoxicity and acute cellular rejection (ACR) is a biopsy, an invasive and expensive procedure. More efficient strategies to screen patients for biopsy are important from the clinical and financial points of view. The aim of this study was to evaluate various artificial intelligence techniques to screen for the need for a biopsy among patients suspected of nephrotoxicity or ACR during the first year after renal transplantation. We used classifiers like artificial neural networks (ANN), support vector machines (SVM), and Bayesian inference (BI) to indicate if the clinical course of the event suggestive of the need for a biopsy. Each classifier was evaluated by values of sensitivity and area under the ROC curve (AUC) for each of the classifiers. The technique that showed the best sensitivity value as an indicator for biopsy was SVM with an AUC of 0.79 and an accuracy rate of 79.86%. The results were better than those described in previous works. The accuracy for an indication of biopsy screening was efficient enough to become useful in clinical practice.

Classification of postural profiles among mouth-breathing children by learning vector quantization.

BACKGROUND: Mouth breathing is a chronic syndrome that may bring about postural changes. Finding characteristic patterns of changes occurring in the complex musculoskeletal system of mouth-breathing children has been a challenge. Learning vector quantization (LVQ) is an artificial neural network model that can be applied for this purpose. OBJECTIVES: The aim of the present study was to apply LVQ to determine the characteristic postural profiles shown by mouth-breathing children, in order to further understand abnormal posture among mouth breathers. METHODS: Postural training data on 52 children (30 mouth breathers and 22 nose breathers) and postural validation data on 32 children (22 mouth breathers and 10 nose breathers) were used. The performance of LVQ and other classification models was compared in relation to self-organizing maps, back-propagation applied to multilayer perceptrons, Bayesian networks, naive Bayes, J48 decision trees, k, and k-nearest-neighbor classifiers. Classifier accuracy was assessed by means of leave-one-out cross-validation, area under ROC curve (AUC), and inter-rater agreement (Kappa statistics). RESULTS: By using the LVQ model, five postural profiles for mouth-breathing children could be determined. LVQ showed satisfactory results for mouth-breathing and nose-breathing classification: sensitivity and specificity rates of 0.90 and 0.95, respectively, when using the training dataset, and 0.95 and 0.90, respectively, when using the validation dataset. CONCLUSIONS: The five postural profiles for mouth-breathing children suggested by LVQ were incorporated into application software for classifying the severity of mouth breathers' abnormal posture.

Application of artificial neural networks in renal transplantation: classification of nephrotoxicity and acute cellular rejection episodes.

Complications associated with kidney transplantation and immunosuppression can be prevented or treated effectively if diagnosed in the early stages by posttransplant monitoring. One of the major problems is diseases that occur during the first year after kidney transplantation. For this purpose, we used different classifiers to predict events of nephrotoxicity versus acute cellular rejection episodes. The classifiers were evaluated according to values of sensitivity, specificity and area under ROC curves (RCA). The classifier with better accuracy rate for nephrotoxicity achieved the value of 75.68% and RCA classifier reached the accuracy of 80.89%. These results are encouraging, with rates of accuracy and error consistent with work purpose.

Fcgamma-receptor IIa polymorphism and the role of immunoadsorption in cardiac dysfunction in patients with dilated cardiomyopathy.

In patients with dilated cardiomyopathy (DCM), cardiac autoantibodies are able to bind with their Fab fragment to epitopes on cardiomyocytes, but thereafter they crosslink through their Fc fragment to cardiac Fc(gamma)-receptor IIa. Polymorphic variability of the Fc(gamma)-receptor IIa is associated with modified affinity of immunoglobin G (IgG) binding and may influence therapeutic effects. In this study, 103 consecutive DCM patients were treated with immunoadsorption (IA) therapy with subsequent IgG substitution (IA/IgG). Echocardiography was performed at baseline and again at 3 and 6 months after IA/IgG. Fc(gamma)-receptor IIa polymorphism R/H131 was genotyped using a nested sequence-specific primer polymerase chain reaction (PCR). Patients with the Fc(gamma)-receptor IIa genotype R/R131 showed significantly greater improvement in left ventricular (LV) function than patients with the R/H131 or H/H131 genotypes did. Irrespective of the Fc(gamma)-receptor polymorphism, patients with shorter disease duration and a more impaired LV function responded with a greater increase in LV ejection fraction (LVEF). Therefore, the Fc(gamma)-receptor polymorphism influences the efficacy of immunomodulatory therapy involving IA/IgG.