Mapping Autoantibodies in Children With Acute Rheumatic Fever.

Background: Acute rheumatic fever (ARF) is a serious sequela of Group A Streptococcus (GAS) infection associated with significant global mortality. Pathogenesis remains poorly understood, with the current prevailing hypothesis based on molecular mimicry and the notion that antibodies generated in response to GAS infection cross-react with cardiac proteins such as myosin. Contemporary investigations of the broader autoantibody response in ARF are needed to both inform pathogenesis models and identify new biomarkers for the disease. Methods: This study has utilised a multi-platform approach to profile circulating autoantibodies in ARF. Sera from patients with ARF, matched healthy controls and patients with uncomplicated GAS pharyngitis were initially analysed for autoreactivity using high content protein arrays (Protoarray, 9000 autoantigens), and further explored using a second protein array platform (HuProt Array, 16,000 autoantigens) and 2-D gel electrophoresis of heart tissue combined with mass spectrometry. Selected autoantigens were orthogonally validated using conventional immunoassays with sera from an ARF case-control study (n=79 cases and n=89 matched healthy controls) and a related study of GAS pharyngitis (n=39) conducted in New Zealand. Results: Global analysis of the protein array data showed an increase in total autoantigen reactivity in ARF patients compared with controls, as well as marked heterogeneity in the autoantibody profiles between ARF patients. Autoantigens previously implicated in ARF pathogenesis, such as myosin and collagens were detected, as were novel candidates. Disease pathway analysis revealed several autoantigens within pathways linked to arthritic and myocardial disease. Orthogonal validation of three novel autoantigens (PTPN2, DMD and ANXA6) showed significant elevation of serum antibodies in ARF (p < 0.05), and further highlighted heterogeneity with patients reactive to different combinations of the three antigens. Conclusions: The broad yet heterogenous elevation of autoantibodies observed suggests epitope spreading, and an expansion of the autoantibody repertoire, likely plays a key role in ARF pathogenesis and disease progression. Multiple autoantigens may be needed as diagnostic biomarkers to capture this heterogeneity.

A longitudinal study of antibody responses to selected host antigens in rheumatic fever and rheumatic heart disease.

Introduction. Group A streptococci can trigger autoimmune responses that lead to acute rheumatic fever (ARF) and rheumatic heart disease (RHD).Gap Statement. Some autoantibodies generated in ARF/RHD target antigens in the S2 subfragment region of cardiac myosin. However, little is known about the kinetics of these antibodies during the disease process.Aim. To determine the antibody responses over time in patients and healthy controls against host tissue proteins - cardiac myosin and peptides from its S2 subfragment, tropomyosin, laminin and keratin.Methodology. We used enzyme-linked immunosorbent assays (ELISA) to determine antibody responses in: (1) healthy controls; (2) patients with streptococcal pharyngitis; (3) patients with ARF with carditis and (4) patients with RHD on penicillin prophylaxis.Results. We observed significantly higher antibody responses against extracellular proteins - laminin and keratin in pharyngitis group, patients with ARF and patients with RHD when compared to healthy controls. The antibody responses against intracellular proteins - cardiac myosin and tropomyosin were elevated only in the group of patients with ARF with active carditis. While the reactivity to S2 peptides S2-1-3, 8-11, 14, 16-18, 21-22 and 32 was higher in patients with ARF, the reactivity in the RHD group was high only against S2-1, 9, 11, 12 when compared to healthy controls. The reactivity against S2 peptides reduced as the disease condition stabilized in the ARF group whereas the reactivity remained unaltered in the RHD group. By contrast antibodies against laminin and keratin persisted in patients with RHD.Conclusion. Our findings of antibody responses against host proteins support the multistep hypothesis in the development of rheumatic carditis. The differential kinetics of serum antibody responses against S2 peptides may have potential use as markers of ongoing cardiac damage that can be used to monitor patients with ARF/RHD.

Unusual presentation of rheumatic fever in a 3-year-old child in the UK.

In the developed world, acute rheumatic fever (ARF) is rare. When it does arise, symptoms commonly include fever, arthralgia and rash. We describe a presentation of a 3-year-old child with ARF in a UK District General Hospital. The patient had a 6-week history of diarrhoea, rash and intermittent right hip arthralgia. This was initially thought to be a viral illness until she re-presented with shortness of breath and fever with a pan-systolic murmur. A throat-culture was negative, but an anti-streptolysin titre was elevated, with a bedside echocardiogram demonstrating moderate to severe mitral regurgitation. The young child was transferred to the local tertiary centre for further management; however, she went on to develop acute left ventricular failure. This case illustrates the need to be vigilant for the presentation of a rare illness, such as rheumatic fever, as there can be significant impacts on the quality of life of young patients.

Are there any novel markers in acute rheumatic fever: neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio.

OBJECTIVE: The aim of this study was to investigate the relationship between C-reactive protein and erythrocyte sedimentation rate and neutrophil-to-lymphocyte, platelet-to-lymphocyte, and monocyte-to-lymphocyte ratios in acute rheumatic fever in children. METHOD: In this retrospective study, 182 patients with acute rheumatic fever and 173 controls were included. Complete blood count parameters, and neutrophil-to-lymphocyte, monocyte-to-lymphocyte, and platelet-to-lymphocyte ratios were recorded for all the patients underwent transthoracic echocardiography. RESULTS: Neutrophil-to-lymphocyte, monocyte-to-lymphocyte, and platelet-to-lymphocyte ratios were significantly higher in patients with rheumatic heart disease than patients without cardiac involvement (p < 0.05). C-reactive protein and erythrocyte sedimentation rate levels were found to have a positive correlation with neutrophil-to-lymphocyte (r = 0.228, p = 0.001; r = 0.355, p = 0.001), platelet-to-lymphocyte (r = 0.227, p = 0.01; r = 0.149, p = 0.005), and monocyte-to-lymphocyte ratios (r = 0.117, p = 0.005; r = 0.107, p = 0.044). Cardiac involvement was present in 152 (83.5%) of the patients. Neutrophil-to-lymphocyte, monocyte-to-lymphocyte, and platelet-to-lymphocyte ratios were significantly higher in patients with rheumatic heart disease than patients without cardiac involvement (p < 0.05). Patients with carditis were grouped according to mitral, aortic, or both valve involvement but there was no significant difference between the groups with respect to neutrophil-to-lymphocyte, monocyte-to-lymphocyte, and platelet-to-lymphocyte ratios. In addition, neutrophil-to-lymphocyte and monocyte-to-lymphocyte ratios were significantly higher in patients with Sydenham's chorea than without chorea (p < 0.05). CONCLUSION: Neutrophil-to-lymphocyte, platelet-to-lymphocyte, and monocyte-to-lymphocyte ratios may help make the diagnosis of acute rheumatic fever and its prognosis by serial measurements in follow-up but none of them tell us the severity of carditis. Also, this is the first study showing the positive correlation between Sydenham's chorea and neutrophil-to-lymphocyte and monocyte-to-lymphocyte ratios. Further studies are needed to confirm this hypothesis, as this is the first study in the literature on this topic.

Sentinel biomarkers in HCV positive patients with mixed cryoglobulinemia.

BACKGROUND: Infections, autoimmunity and cancer play a role as determinants of etiology in Hepatitis C virus (HCV) related mixed cryoglobulinemia (MC). Several factors of risk have been suggested as markers of pathogenesis and progression of HCV-related MC into B cell Non-Hodgkin's Lymphoma (B-NHL). Here, we evaluated IgG subclass distribution, free light chains (FLCs) and vascular endothelial growth factor (VEGF) as a new combination of biomarkers. METHODS: We measured IgG1-4 subclasses, FLCs and VEGF levels in sera 53 from HCV-related MC, in comparison with 40 sera from HCV negative patients with rheumatoid arthritis (RA) and 30 from healthy blood donors (HBD). RESULTS: IgG3 levels were significantly higher in HCV-MC patients with a decrement of IgG2 and IgG4; FLC levels significantly increased in both MC and RA patients' groups; serological VEGF was higher in HCV-MC patients than in HBD in correlation with k and λ levels. CONCLUSION: Our results suggest that a specific IgG subclasses pattern together with raised levels of FLCs and VEGF could represent the biomarker "signature" of an inflammation multistage of acquired immune system.

Systems immunology reveals a linked IgG3-C4 response in patients with acute rheumatic fever.

Acute rheumatic fever (ARF) and chronic rheumatic heart disease (RHD) are autoimmune sequelae of a Group A streptococcal infection with significant global mortality and poorly understood pathogenesis. Immunoglobulin and complement deposition were observed in ARF/RHD valve tissue over 50 years ago, yet contemporary investigations have been lacking. This study applied systems immunology to investigate the relationships between the complement system and immunoglobulin in ARF. Patients were stratified by C-reactive protein (CRP) concentration into high (≥10 µg mL-1 ) and low (<10 µg mL-1 ) groups to distinguish those with clinically significant inflammatory processes from those with abating inflammation. The circulating concentrations of 17 complement factors and six immunoglobulin isotypes and subclasses were measured in ARF patients and highly matched healthy controls using multiplex bead-based immunoassays. An integrative statistical approach combining feature selection and principal component analysis revealed a linked IgG3-C4 response in ARF patients with high CRP that was absent in controls. Strikingly, both IgG3 and C4 were elevated above clinical reference ranges, suggesting these features are a marker of ARF-associated inflammation. Humoral immunity in response to M protein, an antigen implicated in ARF pathogenesis, was completely polarized to IgG3 in the patient group. Furthermore, the anti-M-protein IgG3 response was correlated with circulating IgG3 concentration, highlighting a potential role for this potent immunoglobulin subclass in disease. In conclusion, a linked IgG3-C4 response appears important in the initial, inflammatory stage of ARF and may have immediate utility as a clinical biomarker given the lack of specific diagnostic tests currently available.

Serum periostin levels in acute rheumatic fever: is it useful as a new biomarker?

Background: Acute rheumatic fever (ARF) continues to be a public health problem in low- and middle-income countries. Because there is no specific laboratory test for the exact diagnosis of ARF, the diagnosis is made by the modified Jones criteria. Periostin is an extracellular matrix protein which has been shown to be expressed during remodelling, mechanical stress and tissue repair. There are no data on the relationship between periostin and ARF.Aim: To evaluate serum periostin levels in patients with ARF and investigate its usefulness as a biomarker for diagnosing and monitoring the efficacy of treatment.Methods: Serum periostin levels were estimated in 31 patients with ARF and compared with a control group of 25 healthy patients. The control group comprised patients referred to the outpatient clinic for further evaluation of cardiac murmur, palpitations or chest pain. Patients who were diagnosed with any other cardiac or systemic illness after detailed systemic and cardiac examination were excluded.Results: The mean (SD) age at diagnosis was 12.1 (3.3) years in the patient group, 48.4% of whom were male. There were no significant differences in age or gender between patients and controls. All the study patients had various degrees of carditis, 58.1% had arthritis and 9.6% had Sydenham chorea. Mean (SD) serum periostin levels in patients with ARF on admission [58.4 (13.9) ng/mL] were significantly higher than in the control group [35.1 (10.7) ng/mL, p < 0.01] and were also significantly decreased in the patient group after treatment [35.1 (13.1) ng/mL, p < 0.01]. There was no significant difference in serum periostin levels regarding the severity of carditis in the patient group while patients with any severity of carditis had significantly higher periostin levels than the controls (p < 0.01). Periostin levels were significantly correlated with ESR and CRP values before treatment, but this correlation was detected for only ESR after treatment. For the initial diagnosis of ARF, a serum periostin level of 53.45 ng/mL was found to be the cut-off point with 80.6% sensitivity and 100% specificity.Conclusion: There was a significant increase in serum periostin levels in patients with ARF and a reduction after adequate treatment which was independent of the severity of carditis. Periostin may be a biomarker which acts as an acute phase reactant in ARF.

Value of serum procalcitonin for the diagnosis of bacterial septic arthritis in daily practice in rheumatology.

INTRODUCTION/OBJECTIVES: Septic arthritis is a diagnostic and therapeutic emergency because of a high morbidity and mortality. Nevertheless, the etiologic diagnosis is often difficult. The aim of our study was to determine if serum procalcitonin was a discriminatory biomarker in case of arthritis of undetermined etiology. METHOD: Patients were separated in five groups: gouty arthritis, calcium pyrophosphate deposition arthritis, osteoarthritis or post-traumatic arthritis ("mechanical" arthritis), chronic inflammatory rheumatic arthritis, and septic arthritis. Levels of serum white blood cells, C-reactive protein and procalcitonin were measured. RESULTS: Ninety-eight patients were included: 18 in the "gout" group, 26 in the "calcium pyrophosphate deposition arthritis" group, 16 in the mechanical group, 18 in the "chronic inflammatory rheumatic" group, and 20 in the "sepsis" group. The area under the receiver operating characteristic curve of white blood cells, C-reactive protein, and procalcitonin levels to diagnose a septic arthritis were 0.69 (IC95% 0.55-0.83), 0.82 (IC95% 0.73-0.91), and 0.87 (IC95% 0.76-0.98) respectively. For a cutoff of 0.5 ng/ml, procalcitonin sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio were 65%, 91%, 65%, 91%, 7.2, and 0.4, respectively. Serum C-reactive protein and procalcitonin levels were correlated, were not different in sepsis or gout groups, and were higher in non-septic arthritis with poly-arthritis than with mono-arthritis (p < 0.05). CONCLUSIONS: Serum procalcitonin is a useful biomarker in arthritis management with diagnosis performances higher than those of other biomarkers (white blood cells, C-reactive protein).Key Points• Diagnostic performances of serum procalcitonin level in septic arthritis are higher than those of serum C-reactive protein or white blood cells levels.• Serum procalcitonin levels are not different in septic arthritis or gouty arthritis.• Serum procalcitonin levels are higher in non-septic arthritis with poly-arthritis than with mono-arthritis.

Rituximab in clinical practice: dosage, drug adherence, Ig levels, infections, and drug antibodies.

The objective of this study is to explore the following: (1) the impact of two different initial doses and cumulative 2-year dose of rituximab (RTX) on drug adherence and predictors of adherence to treatment in rheumatoid arthritis (RA) patients in an observational clinical setting, (2) immunoglobulin levels (IgG/IgM/IgA) during repeated treatment and their relation to infections, and (3) development of anti-rituximab antibodies (ADA). All RA patients receiving RTX from January 2003 to April 2012 at the department were included. The initiating doses were 500 or 1000 mg intravenously days 1 and 15. Drug adherence was estimated using life-table. Baseline predictors of adherence to treatment were analyzed using Cox regression model. Levels of immunoglobulins were measured at treatment initiation and before retreatment. Serum levels of RTX and ADA were measured in 96 patients at 6 months using ELISA. One hundred fifty-three patients were included. Seventy-four (48%) started treatment with 500 and 79 (52%) with 1000 mg. No difference in drug adherence was seen between the different initial or cumulative RTX doses. Methotrexate (MTX) use and low DAS28 at baseline predicted better drug adherence. Ig levels decreased with repeated treatments but low levels were not associated with infections. 11/96 patients had developed ADA at 6 months. Long-term adherence to RTX in RA patient was not influenced by starting- or cumulative 2-year doses. MTX use and low DAS28 at baseline was positively associated with drug adherence. Decreasing Ig levels during treatment were not associated with risk of infections. Development of ADA may influence treatment efficacy and tolerability.

Association of rheumatic fever & rheumatic heart disease with plausible early & late-stage disease markers.

BACKGROUND & OBJECTIVES: Rheumatic fever (RF) and rheumatic heart disease (RHD) are the autoimmune sequelae caused by Group A Streptococcus. RHD still remains a major concern in the developing countries due to its poor diagnosis, lack of vaccines and social awareness among population. This study was aimed to identify the plausible early- and late-stage disease markers associated with RF/RHD. METHODS: A total of 84 patients with confirmed pharyngitis (n=18), RF (n=23) and RHD (n=43) were included in the comparative analysis of different factors involved in host-pathogen interaction during RF/RHD pathogenesis. RESULTS: This study revealed high titre of serum antistreptolysin O (ASO) antibody in pharyngitis compared to RF and RHD patients, whereas procollagen type 1 C-peptide (PICP) level was elevated in RHD which showed an inverse correlation with serum ASO titre. The significant elevation of serum anti-peptide associated with RF (PARF) antibody in RF patients was correlated as a probable stage-specific determinant. In addition, pro-inflammatory cytokine profile revealed high levels of interleukin-12 (IL-12)/IL-23p40, IL-17A in RF, whereas IL-6 concentration was higher in RHD compared to healthy controls. INTERPRETATION & CONCLUSIONS: The overall assessment of the factors/ disease markers involved in host-pathogen interaction in RF/RHD may be suggestive of plausible disease marker in different groups of patients. Further studies with larger sample need to be done to better understand RF/RHD pathogenesis.

A novel approach for characterizing variations in serum peptides in rheumatic heart disease.

BACKGROUND & OBJECTIVES: Acute rheumatic fever and rheumatic heart disease (RHD) are important public health problems in developing countries. In this study, peptidomic analyses on RHD patients and healthy individuals were performed to characterize variations in serum peptide levels using label-free quantitation approaches. METHODS: Blood samples were obtained from 160 healthy controls and 160 RHD patients. Of the 448 identified peptides, 272 were analyzed by two label-free mass spectrometry methods, the spectral count and spectral index. RESULTS: There were 38 proteins and 95 peptides with significant (adjusted P<0.001) differences in the abundance of peptides between healthy controls and RHD patients, including multiple peptides derived from histone H2B, villin-like protein, complement C4-B and motile sperm domain containing protein-2. The levels of 10 peptides were upregulated, and 85 peptides were downregulated in patients compared to controls. In addition, in patients, the levels of four proteins were upregulated and 34 were downregulated compared to controls. INTERPRETATION & CONCLUSIONS: This study shows that detection of significant changes in serum peptides reflects the difference between RHD patients and healthy controls. This label-free method may be helpful for clinicians to treat RHD patients during the perioperative period.

Immuno-nephelometric determination of group streptococcal anti-streptolysin O titres (ASOT) from dried blood spots: Method for validating a new assay.

This study was designed to determine the sensitivity and reproducibility of recovering anti-streptolysin O titres (ASOT) from dried blood spot (DBS) samples, a methodologic subcomponent of the penicillin pharmacokinetic studies in children receiving secondary prophylaxis with intramuscular benzathine penicillin for acute rheumatic fever.

Cardiac Myosin Epitopes Recognized by Autoantibody in Acute and Convalescent Rheumatic Fever.

BACKGROUND: Acute rheumatic fever (ARF) is an autoimmune disorder associated with Streptococcus pyogenes infection. A prevailing hypothesis to account for this disease is that epitopes of self-antigens, such as cardiac myosin react to antibodies against S. pyogenes. The goal of our study was to confirm disease epitopes of cardiac myosin, identify immunodominant epitopes and to monitor the epitope response pattern in acute and convalescent rheumatic fever. METHODS: Enzyme-linked immunosorbant assays were used to determine epitopes immunodominant in acute disease and to track the immune response longitudinally to document any changes in the epitope pattern in convalescent sera. Multiplex fluorescence immunoassay was used to correlate anti-streptolysin O (ASO) and anti-human cardiac myosin antibodies. RESULTS: Disease-specific epitopes in rheumatic fever were identified as S2-1, 4 and 8. Epitopes S2-1, 4, 8 and 9 were found to be immunodominant in acute sera and S2-1, 8, 9, 29 and 30 in the convalescent sera. Frequency analysis showed that 50% of the ARF subjects responded to S2-8. S2-8 responders tended to maintain their epitope pattern throughout the convalescent period, whereas the S2-8 nonresponders tended to spread their responses to other epitopes later in the immune response. There was a significant correlation between anti-cardiac myosin and ASO titers. In addition, S2-8 responders showed elevated ASO titers compared with S2-8 non responders. CONCLUSION: Our studies confirm the existence of S2-1, 4 and 8 as disease-specific epitopes. We provide evidence that cardiac myosin S2-8 responders remain epitope stable in convalescence, whereas S2-8 nonresponders shift to neoepitopes. Multiplex data indicated a correlation between elevated ASO and anti-human cardiac myosin antibody titers. Mapping of cardiac myosin epitopes recognized in rheumatic fever sera may identify immunophenotypes of rheumatic fever.

A Case of Adult-Onset Acute Rheumatic Fever With Long-Lasting Atrioventricular Block Requiring Permanent Pacemaker Implantation.

A 45-year-old hypertensive Japanese woman presented with epigastric pain on inspiration, fever, complete atrioventricular block and polyarthritis. Her antistreptolysin O levels were markedly elevated. A diagnosis of rheumatic fever was made according to the modified Jones criteria. She was prescribed loxoprofen sodium, which was partially effective for her extracardiac clinical symptoms. However, she had syncope due to complete atrioventricular block with asystole longer than 10 seconds. Consequently, we implanted a permanent pacemaker. Although we prescribed prednisolone, the efficacy of which was limited for the patient's conduction disturbance, the complete atrioventricular block persisted. In our systematic review of 12 similar cases, the duration of complete heart block was always transient and there was no case requiring a permanent pacemaker. We thus encountered a very rare case of adult-onset acute rheumatic fever with persistent complete atrioventricular block necessitating permanent pacemaker implantation.

An ultra-high performance liquid chromatographic-tandem mass spectrometric method for the determination of sinomenine in human plasma after transdermal delivery of the zhengqing fengtongning injection.

A sensitive, precise and selective ultra-high performance liquid chromatography method coupled with triple-quadrupole mass spectrometry was developed and validated for the determination of trace amounts of sinomenine (ng/mL) in minute volumes of human plasma. Fifty microliter plasma samples were precipitated using methanol to extract sinomenine. Separation was carried out on a C18 column with a water and acetonitrile mobile phase gradient with formic acid as an additive. The mass spectrometry data were obtained in the positive ion mode, and the transition of multiple reactions was monitored at m/z 330.2→181.0 for sinomenine quantification. The working assay range for sinomenine was linear from 0.1173 to 15.02 ng/mL with the lower limit of quantification of 0.1173 ng/mL. The precision and accuracy of the method was less than 15% in intra-day and inter-day experiments with a matrix effect of less than 6.5%. After validation, the quantitative method was applied to analyze sinomenine levels in human plasma after transdermal delivery of the Zhengqing Fengtongning Injection. The results showed that some samples contained sinomenine within the concentration range 0.4131-4.407 ng/mL.

Septic arthritis and acute rheumatic fever in children: the diagnostic value of serological inflammatory markers.

INTRODUCTION: Joint pain and raised inflammatory markers are features of both acute rheumatic fever (ARF) and septic arthritis, often posing a diagnostic challenge to clinicians. Important differences in the presenting serological inflammatory marker profile may assist patient diagnosis, however, as clinical experience suggests that ARF is associated with a higher erythrocyte sedimentation rate (ESR), whereas other serological markers may be similarly elevated in these 2 conditions. OBJECTIVE: The goal of this study was to determine the diagnostic value of serological inflammatory markers and white cell count (WCC) in children presenting with acute joint pain secondary to ARF or septic arthritis. METHODS: Data were obtained from the Auckland regional rheumatic fever database and hospital computer records between 2005 and 2012. Records of all patients under the age of 16 years who were admitted with a new diagnosis of ARF or septic arthritis were analyzed. The diagnosis of ARF was defined on the basis of the New Zealand modification of the Jones Criteria, and the diagnosis of septic arthritis was defined on the basis of joint fluid cytology and culture. Baseline characteristics, serological inflammatory markers, and serum WCC were compared between the ARF and septic arthritis patient groups. RESULTS: Children with ARF displayed significantly higher ESR, higher serum C-reactive protein, and lower serum WCC than children with septic arthritis on presentation to hospital. In children presenting with monoarthritis, an ESR>64.5, serum WCC<12.1×109/L, and age above 8.5 years were found to be significant independent predictors of ARF. Children with all 3 predictors had a 71% risk for ARF and a 29% risk for septic arthritis. A significant proportion (30%) of children with the final diagnosis of ARF initially presented with monoarthritis; 14% of these children (5/34) had received nonsteroidal anti-inflammatory medication before hospital presentation, and 74% of these children (25/34) had abnormal echocardiograms on admission. CONCLUSIONS: ARF and septic arthritis are important diagnoses to consider in children presenting with acute joint pain in New Zealand. A significant proportion of patients with ARF initially present with acute monoarthritis. Serological inflammatory markers and WCC on presentation differ significantly between children with ARF and septic arthritis.

Plasma gelsolin as a biomarker of acute rheumatic carditis.

BACKGROUND: Acute rheumatic fever is an autoimmune, inflammatory, and multi-systemic disease secondary to pharyngitis and is caused by group A streptococcus. In developing countries, acute rheumatic fever is the most common cause of acquired heart disease. Gelsolin is a calcium-dependent, multi-functional actin-regulatory protein circulating in the plasma of healthy human beings. The correlation between blood gelsolin levels and inflammatory conditions suggests the potential benefit of gelsolin as a prognostic marker. The aim of the present study was to appraise the association of gelsolin and acute rheumatic carditis in childhood. MATERIALS AND METHODS: Plasma gelsolin levels were measured and echocardiographic examinations were performed in patients (n=37) with acute rheumatic carditis and compared with those of age- and gender-matched healthy controls (n=24). RESULTS: The plasma gelsolin levels in children with acute rheumatic carditis were significantly lower compared with controls (197±218 versus 322±255 mg/L, p=0.039). There was a significant correlation among gelsolin levels and the grade of mitral regurgitation (p=0.030), left ventricular end-diastolic diameter (p=0.017), and left ventricular end-systolic diameter (p=0.028) at diagnosis. CONCLUSIONS: Levels of the gelsolin plasma isoform were decreased in patients with acute rheumatic carditis compared with healthy controls. Gelsolin may be used as a biochemical marker for acute rheumatic carditis.

Plasma adiponectin levels and relations with cytokines in children with acute rheumatic fever.

AIM: We aimed to investigate the role of adiponectin in acute rheumatic fever by evaluating correlations with cytokines and acute-phase reactants. METHODS: Patients were divided into three groups by clinical findings. Group 1 included 8 patients with only chorea, Group 2 included 13 patients with arthritis and carditis, and Group 3 included 12 patients with only carditis. A total of 54 age- and gender-matched children were enrolled in the control group. Blood samples were drawn for analysing acute-phase reactants, adiponectin, tumour necrosis factor-α, interleukin-6, and interleukin-8 levels at baseline on Days 2, 5, 10, and 15, and at 8 weeks. RESULTS: There was no statistically significant difference between baseline age, gender, body mass index, serum triglyceride, total cholesterol, and low-density lipoprotein levels of the study and control groups (p>0.05). No correlation was found between baseline plasma adiponectin levels, age, body mass index, follicle-stimulating hormone, luteinising hormone, oestradiol, total testosterone, and blood lipid levels of the study and control groups (p>0.05). We found that adiponectin and interleukin-6 levels increased, tumour necrosis factor-α levels decreased, and interleukin-8 levels remained unchanged in acute rheumatic fever, which is an inflammatory disease. Moreover, adiponectin level was higher and tumour necrosis factor-α level was lower in the improvement period in comparison with the acute period, particularly in the carditis group. CONCLUSION: It was considered that, increasing throughout the treatment period, adiponectin may have anti-inflammatory effects in acute rheumatic fever. In addition, adiponectin levels are associated with a decline in inflammatory mediators in rheumatic fever.