Evaluation of hematological parameters in children with FMF.

In this study, we aimed to investigate whether neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and mean platelet volume (MPV) might be helpful in the diagnosis of subclinical inflammation of familial Mediterranean fever (FMF). Clinical, laboratory, and genetic results of the patients who were followed up with the diagnosis of FMF were obtained retrospectively from the hospital files and recorded to standardized form. Age- and sex-matched healthy subjects were included as the control group. Eighty-three of the 143 patients (58.0%) were male and 60 (42.0%) were female. The mean age of our patients was 164.62 ± 51.20 months and the mean age of the control group was 164.92 ± 51.10 months. The mean diagnosis age of our patients was 98.10 ± 49.11 months. The mean follow-up time of the patients was 66.03 ± 36.37 months. 91.60% of our patients had abdominal pain, 78.32% fever, and 28.67% joint pain. The mean NLR of the patients was significantly higher than the mean levels at attack-free period and the control group. However, no statistically significant difference was found between the mean levels at attack-free period and the control group. MPV levels were statistically significantly high during acute attack when compared with the control group. However, they showed no statistically significant difference between acute attack and attack-free period. NLR is a useful marker to predict inflammation in FMF patients. However, our results did not support the idea that MPV might reflect acute attack and attack-free period.

Asociación entre el reflujo vesicoureteral y la nefroesclerosis en las infecciones urinarias / Association of vesicoureteral reflux and renal scarring in urinary tract infections

Introducción. El objetivo del estudio fue investigar la relación entre reflujo vesicoureteral (RVU) y daño renal en pacientes con infección urinaria (IU) sin fiebre, primera IU febril e IU recurrente. El objetivo secundario, determinar si la proteína C-reactiva (PCR) actuaría como predictor de nefroesclerosis en las IU febriles. Población y métodos. Estudio prospectivo; pacientes pediátricos con IU sin fiebre, primera IU febril e IU recurrente. Los análisis de laboratorio de rutina incluyeron hemograma completo, urea, creatinina, análisis de orina completamente automatizado, urocultivo y PCR. Se realizó ecografía urológica luego del diagnóstico de IU, cistouretrografía miccional tras seis semanas y gammagrafía renal estática con ácido dimercaptosuccínico marcado con 99mTc tras seis meses a todos los participantes. Resultados. Participaron 47 niños con IU sin fiebre, 48 con primera IU febril y 61 con IU recurrente. Hubo una diferencia estadísticamente significativa entre los grupos respecto de RVU y nefroesclerosis (p= 0,001 y p= 0,011, respectivamente). También hubo una diferencia estadísticamente significativa respecto de nefroesclerosis entre los pacientes con y sin RVU (p= 0,001). Además, se estableció una diferencia estadísticamente significativa respecto de nefroesclerosis (p < 0,05) en los pacientes con PCR cinco veces mayor o menor que el valor de corte aceptado (5 mg/dl). Conclusión. La proporción de nefroesclerosis fue paralela a la frecuencia de RVU. Cuanto mayor era el grado de RVU, mayor era el daño renal. Se determinó una correlación positiva entre PCR elevada y nefroesclerosis, lo que señala esclerosis durante el diagnóstico de pielonefritis.

Introduction. The aim was to investigate the relationship between vesicoureteral reflux (VUR) and renal damage in non-febrile, febrile for the first time and recurrent urinary tract infection (UTI) patients. The secondary aim was to determine whether C-reactive protein (CRP) in febrile UTIs could be a predictor of renal scarring. Population and methods. This prospective study included non-febrile, febrile for the first time and recurrent pediatric UTI cases. The routine lab analyses comprised a complete blood count, urea, creatinine, fully automated urinalysis, urine culture and CRP analyses. All the participants were examined using urine ultrasonography subsequent to their UTI diagnosis, voiding cystourethrography (VCUG) after six weeks and Tc-99m dimercaptosuccinic acid (DMSA) static renal scintigraphy after six months. Results. There were included 47 children with non-febrile UTIs, 48 with first febrile UTIs and 61 with recurrent UTIs. A statistically significant difference was found among the groups in terms of VUR and renal scarring (p= 0.001 and p= 0.011, respectively). A statistically significant difference was also found in terms of renal scarring between patients with and without VUR (p= 0.001). Moreover, a statistically significant difference was also present in relation to renal scarring (p <0.05) in patients with five-fold lower or higher CRP values than the accepted cut-off value (5mg/dl). Conclusion. The ratio of renal scars detected was found to be parallel to the VUR frequency. The higher the VUR grade, the more renal damage was found. A positive correlation between elevated CRP and renal scarring was determined, indicating the presence of scarring during the diagnosis of pyelonephritis.

Association of vesicoureteral reflux and renal scarring in urinary tract infections. / Asociación entre el reflujo vesicoureteral y la nefroesclerosis en las infecciones urinarias.

INTRODUCTION: The aim was to investigate the relationship between vesicoureteral reflux (VUR) and renal damage in non-febrile, febrile for the first time and recurrent urinary tract infection (UTI) patients. The secondary aim was to determine whether C-reactive protein (CRP) in febrile UTIs could be a predictor of renal scarring. POPULATION AND METHODS: This prospective study included non-febrile, febrile for the first time and recurrent pediatric UTI cases. The routine lab analyses comprised a complete blood count, urea, creatinine, fully automated urinalysis, urine culture and CRP analyses. All the participants were examined using urine ultrasonography subsequent to their UTI diagnosis, voiding cystourethrography (VCUG) after six weeks and Tc-99m dimercaptosuccinic acid (DMSA) static renal scintigraphy after six months. RESULTS: There were included 47 children with non-febrile UTIs, 48 with first febrile UTIs and 61 with recurrent UTIs. A statistically significant difference was found among the groups in terms of VUR and renal scarring (p= 0.001 and p= 0.011, respectively). A statistically significant difference was also found in terms of renal scarring between patients with and without VUR (p= 0.001). Moreover, a statistically significant difference was also present in relation to renal scarring (p <0.05) in patients with five-fold lower or higher CRP values than the accepted cut-off value (5mg/dl). CONCLUSION: The ratio of renal scars detected was found to be parallel to the VUR frequency. The higher the VUR grade, the more renal damage was found. A positive correlation between elevated CRP and renal scarring was determined, indicating the presence of scarring during the diagnosis of pyelonephritis.

Introducción. El objetivo del estudio fue investigar la relación entre reflujo vesicoureteral (RVU) y daño renal en pacientes con infección urinaria (IU) sin fiebre, primera IU febril e IU recurrente. El objetivo secundario, determinar si la proteína C-reactiva (PCR) actuaría como predictor de nefroesclerosis en las IU febriles. Población y métodos. Estudio prospectivo; pacientes pediátricos con IU sin fiebre, primera IU febril e IU recurrente. Los análisis de laboratorio de rutina incluyeron hemograma completo, urea, creatinina, análisis de orina completamente automatizado, urocultivo y PCR. Se realizó ecografía urológica luego del diagnóstico de IU, cistouretrografía miccional tras seis semanas y gammagrafía renal estática con ácido dimercaptosuccínico marcado con 99mTc tras seis meses a todos los participantes. Resultados. Participaron 47 niños con IU sin fiebre, 48 con primera IU febril y 61 con IU recurrente. Hubo una diferencia estadísticamente significativa entre los grupos respecto de RVU y nefroesclerosis (p= 0,001 y p= 0,011, respectivamente). También hubo una diferencia estadísticamente significativa respecto de nefroesclerosis entre los pacientes con y sin RVU (p= 0,001). Además, se estableció una diferencia estadísticamente significativa respecto de nefroesclerosis (p < 0,05) en los pacientes con PCR cinco veces mayor o menor que el valor de corte aceptado (5 mg/dl). Conclusión. La proporción de nefroesclerosis fue paralela a la frecuencia de RVU. Cuanto mayor era el grado de RVU, mayor era el daño renal. Se determinó una correlación positiva entre PCR elevada y nefroesclerosis, lo que señala esclerosis durante el diagnóstico de pielonefritis.

Occult Disseminated Tuberculosis with Holocord Longitudinally Extensive Transverse Myelitis: A Rare Phenomenon in a Child.

Longitudinally extensive transverse myelitis (LETM) is defined as an inflammatory lesion of the spinal cord that extends to three or more segments. LETM is a commonly characteristic feature of neuromyelitis optica (NMO) or various autoimmune diseases. Manifestation of Mycobacterium tuberculosis (MTB) infection with LETM are rare and usually in the cervicothoracic spinal cord. Our patient presented with holocord LETM, so NMO was considered initially diagnosis. After in further research, MTB was diagnosed and treated successfully. The current case underscores that tuberculosis must be keep in mind when undertaking differential diagnosis of demyelinating diseases even in the absence of symptoms of infection, and especially in endemic regions.

A novel assessment tool for clinical care of patients with autoinflammatory disease: juvenile autoinflammatory disease multidimensional assessment report.

OBJECTIVES: To develop and test a new multidimensional questionnaire for assessment of children with auto-inflammatory disease (AID) such as FMF, PFAPA, HIDS, TRAPS in standard clinical care. METHODS: The juvenile auto-inflammatory disease multidimensional assessment report (JAIMAR) includes 16 parent or patient-centered measures and four dimensions that assess functional status, pain, therapeutic compliance and health-related quality of life (physical, social, school, emotional status) with disease outcome. It is proposed for use as both a proxy-report and a patient self-report, with the suggested age range of 8-18 years for use as a self-report. RESULTS: 250 children with FMF were included in the study. Total of 179 forms were filled up by parents and patients, and 71 forms were filled up by parents having children less than 8 years. Completing and scoring the JAIMAR can be done in 15 minutes. For the JAIMAR's dimensions, the Cronbach's alpha coefficient for internal consistency was between 0.507-0.998. There was a significant and a positive correlation between the test-retest scale scores (ICC=0.607-0.966). Concerning construct validity, all factors loadings were above 0.30. For the criterion validity, the correlation level between each dimension and the related scale ranged from medium (r=0.329, p<0.0001) to large (r=0.894, p<0.0001). The parents' proxy-reported and children's self-reported data were outstandingly concordant (r=0.770-0.989). CONCLUSIONS: The development of the JAIMAR introduces a new and multi-dimensional approach in paediatric rheumatology practice. It is a new tool for children with auto-inflammatory dis-ease and it may help enhance their quality of care.

Comparison of the efficacy of once- and twice-daily colchicine dosage in pediatric patients with familial Mediterranean fever--a randomized controlled noninferiority trial.

BACKGROUND: In this study, we examined the efficacy and safety of a once-daily dosage schema of colchicine compared with a twice-daily dosage schema in pediatric patients with familial Mediterranean fever (FMF). METHODS: In this 24-week, multicenter, randomized controlled noninferiority trial, pediatric patients newly diagnosed with FMF carrying a homozygous or compound heterozygous mutation and not receiving any treatment were included. Patients were randomly assigned using a block randomization method to receive treatment with a once- or twice-daily dosage. Clinical and laboratory characteristics and medication side effects were recorded and compared between groups. The study was carried out in compliance with Good Clinical Practice and the Consolidated Standards for Reporting of Trials (CONSORT) statement. RESULTS: A total of 92 patients were selected, and 79 patients completed the study. There were 42 patients in the once-daily dosage group and 37 in the twice-daily dosage group. The results indicated that the once-daily dosage was not inferior to the twice-daily dosage regarding decrease in attack frequency and duration as well as improvement in clinical findings and Mor severity scores. Alterations in laboratory findings indicating inflammation, such as erythrocyte sedimentation rate, C-reactive protein, and serum amyloid A, were similar in both groups. The rates of drug side effects were similar between the once- and twice-daily dosage groups, implying comparable safety of colchicine, with the exception of diarrhea, which was slightly higher in the once-daily dosage group. CONCLUSIONS: Using colchicine with either a once- or twice-daily dosage provides similar clinical and laboratory improvements. Considering both efficacy and safety, colchicine can be prescribed with a once-daily dosage. TRIAL REGISTRATION ID: ClinicalTrials.gov identifier NCT02602028 . Registered 5 November 2015.

Development of a medication adherence scale for familial Mediterranean fever (MASIF) in a cohort of Turkish children.

OBJECTIVES: To develop and assess the validity and reliability of an adherence scale concerning medical treatment in paediatric FMF patients. METHODS: The Medication Adherence Scale in FMF Patients (MASIF) is a 18-item questionnaire that evaluates adherence to medication in four domains. Validation of the instrument was accomplished in paediatric FMF patients (aged 2-18 years) under medication at least for 6 months. The first step was to build up the scale through qualitative approach (with interviews using semi-structured questions). Validation analyses included assessment of feasibility, face and content validity; construct validity, internal consistency and test-retest reliability. RESULTS: One hundred and fifty patients with FMF were enrolled in the study. The mean age of the patients was 11.11±4.02 years and 48.7% of them were male. The MASIF was found to be feasible and valid for both face and content. It correlated with the Morisky Medication Adherence Scale as a gold standard thereby demonstrating good construct validity (r=0.515, p<0.001). Assessment of content validity identified four subscales. The internal consistency, Cronbach's alpha was 0.728. There was a positive and significant correlation between test and retest scores (r=0.843; p<0.001). Also, a significant correlation between parents' and children's reports (r=0.781, p<0.001). CONCLUSIONS: Based on these results, the use of this scale to assess and follow up the adherence to treatment in paediatric FMF patients under medical treatment is recommended.

Kocher-Debré-Semelaigne syndrome with rhabdomyolysis and increased creatinine.

Association of Kocher-Debré-Semelaigne syndrome-a myopathy of hypothyroidism in childhood characterized by muscular hypertrophy, with rhabdomyolysis is very rare. We present a case of Kocher-Debré-Semelaigne syndrome with rhabdomyolysis secondary to Hashimoto's thyroiditis. He had muscular symptoms simulating poly/dermatomyositis, massively elevated creatine kinase (CK) levels and high creatinine levels. All of the findings reversed on treatment of hypothyroidism. The response to the therapy strongly suggested that Kocher-Debré-Semelaigne (KDS) syndrome was the underlying etiology. Serum thyroid- stimulating hormone levels should be routinely determined in all patients with muscular symptoms and/or elevation of CK and creatinine, keeping KDS syndrome in mind.

Chondrocalcinosis related to familial hypomagnesemia with hypercalciuria and nephrocalcinosis.

Calcium pyrophosphate dehydrate (CPPD) crystal deposition disease (also known as chondrocalcinosis, CC) is a rare metabolic arthropathy mostly seen in elderly patients. Chondrocalcinosis may be associated with metabolic diseases such as hypomagnesemia when it occurs in young people. We report here a case with hypomagnesemia due to familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) who developed CC during clinical follow-up. To our best knowledge this is the first case of a young patient with CPPD associated with FHHNC.

Does oxybutynin hydrochloride cause arrhythmia in children with bladder dysfunction?

AIM: Pediatric surgeons frequently encounter children presenting with voiding dysfunction symptoms, including urgency, frequency, and incontinence. Antimuscarinic agents Oxybutynin) are the main drugs used to treat patients with overactive bladder (OAB) syndrome, defined as urgency, with or without urgency incontinence, usually with increased daytime frequency and nocturia. Increased QT dispersion is known to be the cause of ventricular arrhythmia in various systemic diseases and leads to increased mortality and morbidity. METHOD: This study represents a subset of a complete data set, considering only those children aged admitted to the Pediatric Surgery and Pediatric Nephrology Clinics during the period January 2011 to July 2012. RESULT: In this study, we have determined that the QT interval changes significantly depending on the use of oxybutynin. The QT changes increased cardiac arrhythmia in children. CONCLUSION: For this reason, children using such drugs should be closely monitored for cardiac arrhythmia.

P-wave duration and dispersion in children with uncomplicated familial Mediterranean fever.

OBJECTIVES: This was a prospective controlled study to determine the P-wave duration (Pdu) and P-wave dispersion (Pd) in patients with familial Mediterranean fever (FMF). METHODS: The study group consisted of 26 children with uncomplicated FMF and 25 age- and sex-matched healthy controls. We performed electrocardiography (ECG) with Doppler echocardiography on patients and controls. All participants underwent 12-lead electrocardiography under strict standards. Pdu and Pd were computed from a randomly selected beat and from an averaged beat constructed from 12 beats, included in a 10-s ECG. RESULTS: The left ventricle (LV) dimensions, LV ejection fraction (LVEF), and LV fractional shortening (LVFS) values, left atrium dimension, and aortic dimension were in normal range in both groups. There were significant differences between the groups regarding LV-isovolumic relaxation time (IRT), LV-isovolumic contraction time (ICT), right ventricle (RV)-ICT, RV-IRT, and Pd (all p < 0.0001). However, highly significant positive correlation was detected between LV-ICT, LV-IRT, RV-ICT, RV-IVT, C-reactive protein (CRP), and Pd (r = 0.505, p < 0.0001; r = 0.483, p < 0.0001; r = 0.433, p = 0.001; r = 0.421, p = 0.001; r = 0.452, p = 0.001; r = 0.478, p < 0.0001, respectively). CONCLUSIONS: Uncomplicated FMF children who are continuously treated with colchicine and do not develop amyloidosis have abnormal atrial dispersion and therefore seemingly have an increased electrocardiographic risk of atrial fibrillation.

Evaluation of the current disease severity scores in paediatric FMF: is it necessary to develop a new one?

OBJECTIVES: Modified adult disease severity scoring systems are being used for childhood FMF. We aim to test the clinical consistency of two common severity scoring systems and to evaluate the correlation of scores with the type of FMF mutations in paediatric FMF patients since certain mutations are prone to severe disease. METHODS: Two hundred and fifty-eight children with FMF were cross-sectionally studied. Assessment of the disease severity was performed by using the modified scoring systems of Mor et al. and Pras et al. Genetic analysis was performed using PCR and restriction endonuclease digestion methods for the presence of 15 FMF gene mutations. FMF mutations were grouped into three based on well-known genotypic-phenotypic associations. Correlation between the mutation groups and the severity scoring systems was assessed. The consistency of the severity scoring systems was evaluated. RESULTS: The results of two scoring systems were not statistically consistent with each other (κ = 0.171). This inconsistency persisted even in a more homogeneous subgroup of patients with only homozygote mutations of M694V, M680I and M694I (κ = 0.125). There was no correlation between the mutation groups and either of the scoring systems (P = 0.002, r = 0,196 for scoring systems of Mor et al.; P = 0.009, r = 0.162 for Pras et al.). CONCLUSIONS: The inconsistency of the two scoring systems and lack of correlation between the scoring systems and mutation groups raises concerns about the reliability of these scoring systems in children. There is a need to develop a scoring system in children based on a prospective registry.

Etiology and outcome of acute kidney injury in children.

The aim of this prospective, multicenter study was to define the etiology and clinical features of acute kidney injury (AKI) in a pediatric patient cohort and to determine prognostic factors. Pediatric-modified RIFLE (pRIFLE) criteria were used to classify AKI. The patient cohort comprised 472 pediatric patients (264 males, 208 females), of whom 32.6% were newborns (median age 3 days, range 1-24 days), and 67.4% were children aged >1 month (median 2.99 years, range 1 month-18 years). The most common medical conditions were prematurity (42.2%) and congenital heart disease (CHD, 11.7%) in newborns, and malignancy (12.9%) and CHD (12.3%) in children aged >1 month. Hypoxic/ischemic injury and sepsis were the leading causes of AKI in both age groups. Dialysis was performed in 30.3% of newborns and 33.6% of children aged >1 month. Mortality was higher in the newborns (42.6 vs. 27.9%; p < 0.005). Stepwise multiple regression analysis revealed the major independent risk factors to be mechanical ventilation [relative risk (RR) 17.31, 95% confidence interval (95% CI) 4.88-61.42], hypervolemia (RR 12.90, 95% CI 1.97-84.37), CHD (RR 9.85, 95% CI 2.08-46.60), and metabolic acidosis (RR 7.64, 95% CI 2.90-20.15) in newborns and mechanical ventilation (RR 8.73, 95% CI 3.95-19.29), hypoxia (RR 5.35, 95% CI 2.26-12.67), and intrinsic AKI (RR 4.91, 95% CI 2.04-11.78) in children aged >1 month.

Sulphasalazine treatment in protracted familial Mediterranean fever arthritis.

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by self-limited attacks of fever and polyserositis. Articular involvement in early-onset FMF is a common finding characterized by non-erosive, generally asymmetric monoarthritis in large joints. Protracted FMF arthritis was reported in 2.6% of Turkish patients. An 8-year-old female who has a history of FMF for 5 years applied to our hospital with complaints of persistent swelling and pain of her left knee for 8 months. The patient had been tried to be managed with non-steroidal anti-inflammatory drugs as well as intra-articulary steroids and colchicine. However, arthritis and acute phase response persisted. With sulphasalazine, complete recovery was achieved. It is our belief that sulphasalazine can be a choice of medical treatment in protracted FMF arthritis.

Chronic kidney disease in children in Turkey.

To determine the incidence, etiology and treatment patterns of chronic kidney disease (CKD) in children a questionnaire was sent to pediatric nephrology centers in Turkey, asking them to report patients under the age of 19 years who had estimated glomerular filtration rates (GFRs) of

Left ventricular diastolic function evaluated with tissue Doppler imaging in children with familial Mediterranean fever.

The aim of this study was to assess the left ventricular diastolic function using conventional echocardiography and tissue Doppler imaging in children with familial Mediterranean fever. This study included 29 (13 males and 16 females) patients and 30 healthy subjects as controls. Body mass index was calculated and arterial blood pressure was monitored. After an overnight fast, venous blood samples were taken and serum amyloid A protein, C-reactive protein, serum-fasting glucose, total cholesterol, triglycerides, high-density lipoprotein cholesterol, very low density lipoprotein cholesterol, and serum low-density lipoprotein cholesterol levels were measured. A complete 2-dimensional, M-mode, pulse wave Doppler, and pulse wave tissue Doppler echocardiographic examination was performed. There were no significant differences between the groups regarding age, body mass index values, systolic and diastolic blood pressures, heart rates, serum-fasting glucose, total cholesterol, triglycerides, high-density lipoprotein cholesterol, very low density lipoprotein cholesterol, and serum low-density lipoprotein cholesterol. Serum levels of inflammatory markers were higher in patients' group (C-reactive protein and serum amyloid A protein levels were 10.84 mg/dl, 22.32 mg/l in patients' group, respectively, and 4.11 mg/dl, 3.65 mg/l, respectively, in the healthy controls.) Peak mitral A wave, E and A wave ratio differed significantly in both groups. There were statistically significant differences regarding parameters observed by tissue Doppler imaging such as E'm, A'm, E'm, and A'm ratio between patients' group and controls. Tissue Doppler imaging provided additional information on left ventricular diastolic function. While systolic functions were in normal range, some of the diastolic function parameters were impaired in patients with familial Mediterranean fever during childhood.

The relationship between urinary tract infections and vesicoureteral reflux in Turkish children.

Early determination of renal scar development risk in children following first urinary tract infection (UTI) and early detection and treatment of vesicoureteral reflux (VUR) are important to prevent renal functional impairment. The aim of this study was to determine the prevalence of VUR and associated renal scar formation, in children who had acute pyelonephritis (APN), first afebrile UTI, and recurrent afebrile UTIs. Patient records of 642 children having UTI were scrutinized and 278 out of 642 were enrolled in this study. The patients were divided into three groups: Group 1, patients with APN (n = 73); Group 2, patients with the first afebrile UTI (n = 88); and group 3, patients with recurrent afebrile UTIs (n = 117). Among these groups, VUR prevalence did not differ significantly (group 1: 24.6%, group 2: 22.7%, and group 3: 26.4%. Renal scarring was detected in 19.3% of the patients and was remarkably lower in group 2 when compared with the other two groups (P < 0.05). Renal scarring was found in 37.1% of the patients with VUR, whereas it was found in 14.3% of patients without VUR. Renal scarring incidence was remarkably higher in patients with grades 4-5 VUR (61.5%) compared with those with grades 1-3 VUR (30.6%) (P = 0.055). In conclusion, since VUR was demonstrated in as many as one-quarter of patients with the first afebrile UTI and VUR incidence did not differ significantly among the groups, all UTIs, lower and upper ones, should be carefully evaluated.

CTLA-4 +49 A/G genotype and HLA-DRB1 polymorphisms in Turkish patients with Henoch-Schönlein purpura.

The pathogenesis of Henoch-Schönlein purpura (HSP) remains unknown; however, it is generally considered to be an immune complex-mediated disease. Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) is expressed on activated T cells, and, thus, it is critically involved in the immune response. We aimed to investigate the possible influence of CTLA-4 polymorphisms for susceptibility to HSP and determine if there were associations with human leukocyte antigen (HLA)-DRB1 genotypes. Using polymerase chain reaction-based DNA genotyping, we investigated the polymorphisms located in the genes encoding CTLA-4 in 100 patients with HSP and 156 ethnically matched healthy controls. When CTLA-4 +49 A/G polymorphism of HSP patients and control group was compared, no associations with joint, gastrointestinal or renal manifestations, or susceptibility to HSP, were observed. However, patients with nephrotic proteinuria had higher HLA-DRB1*13 positivity [odds ratio (OR) = 3.76, 95% confidence interval (95%CI) = 1.25-11.23, P = 0.025]. When the patients were stratified according to CTLA-4 polymorphism, a significant association between nephrotic proteinuria patients and carriage of the AG genotype was also found (OR = 15.42, 95%CI = 1.59-148.82, P = 0.008). These results suggested that CTLA-4 +49 A/G polymorphism does not contribute to susceptibility to HSP; however, the presence of CTLA-4 AG genotype and HLA-DRB1*13 could be a risk factor for developing nephrotic-range proteinuria in these patients.

HLA-DRB1 alleles and Henoch-Schönlein purpura: susceptibility and severity of disease.

OBJECTIVE: The genetic basis of susceptibility to Henoch-Schönlein purpura (HSP) may be conferred by a number of gene loci, including the MHC. Associations between human leukocyte antigen (HLA) and disease can help to establish a basis for susceptibility and assist in the prediction of the outcome and clinical heterogeneity. We aimed to investigate the implications of the HLA-DRB1 locus and the susceptibility to HSP, and to determine if there are associations with joint, gastrointestinal, and renal manifestations of the disease. METHODS: We studied 110 Turkish patients (men/women: 66/44) with HSP. Patients and ethnically matched controls with respect to age and sex (n = 250) were HLA-DRB1 genotyped from DNA determined using molecular based methods. RESULTS: HLA-DRB1 genotype differences between patients with HSP and controls were observed. The frequency of HLA-DRB1 11/14 was higher [odds ratio (OR) 1.97, 95% confidence interval (95% CI) 1.25-3.12, p = 0.003; OR = 1.83, 95% CI = 1.02-3.28, p = 0.035, respectively] and the frequency of HLA-DRB1 10/17 was lower (OR = 1.04, 95% CI = 1.01-1.86, p = 0.035; OR = 3.96, 95% CI = 1.17-13.33, p = 0018, respectively) in patients with HSP compared to controls. No HLA-DRB1 associations with gastrointestinal and renal manifestations were found (p > 0.05). In contrast, HLA-DRB1*11 positivity was increased and HLA-DRB1 14 positivity reduced in HSP patients with joint manifestations (OR = 2.68, 95% CI = 1.09-6.66, p = 0.029; OR = 9.34, 95% CI = 3.38-25.64, p = 0.000, respectively). Also, HLA-DRB1 13 positivity was found to be increased in patients with nephrotic proteinuria (OR = 3.76, 95% CI = 1.25-11.23, p = 0.025). CONCLUSION: These results suggest that genetic factors from HLA-DRB1 genotypes might be related to the susceptibility to HSP for Turkish children but not to the severity of this disease. Additional studies are required to confirm the association of alleles encoded in the HLA region with the disease progression and severity.