Sickle cell anemia (SCA) is a hemoglobinopathy presenting severe endothelial damage associated with increased prevalence of hypertension (HTN). Few studies have used ambulatory blood pressure ...monitoring (ABPM) in pediatric patients with SCA. The aim of this study was to characterize the ABPM profile in children with SCA.
A retrospective cross-sectional study was conducted on all subjects <18 years of age with SCA who presented at a medical reference center in the city of Cartagena, Colombia. Anthropometric, clinical laboratory, treatment, and ABPM parameters, including ambulatory arterial stiffness index (AASI) were registered.
The study included 79 patients, of these, 23 (29%) children had normal BP, 49 (62%) had abnormal BP and 7 (9%) had HTN. Mean age was 10.5 ± 3.6 years and 44 (56%) cases were male. Forty-eight (60%) patients had pre-HTN. Masked HTN was present in 6 (8%) patients. One (1%) had ambulatory HTN, and another one (1%) had white coat HTN. The HTA group exhibited significantly higher systolic BP and diastolic BP compared to the other groups in 24-hour BP readings, daytime BP, and night-time BP ABPM parameters ( P < 0.05), except for daytime DBP ( P = 0.08). Mean AASI was 0.4 ± 0.2. The HTN group had the highest AASI value compared to the other groups ( P = 0.006).
Significant alterations in ABPM parameters are frequently observed in pediatric patients with SCA. The incorporation of ABPM, along with the assessment of AASI, is recommended for a comprehensive evaluation of cardiovascular and renal risk in SCA patients.
Background
Adiponectin and leptin are pivotal in the regulation of metabolism. Pediatric lupus nephritis (pLN), a manifestation of childhood systemic lupus erythematosus (SLE) affecting the kidneys, ...is associated with impaired adipokine levels, suggesting a role in pLN pathogenesis. The aim of this study was to explore the potential relationship between specific single-nucleotide polymorphisms (SNPs)—methylenetetrahydrofolate reductase (MTHFR) rs1801131 and fibrinogen gamma chain (FGG) rs2066865—and the serum levels of leptin and adiponectin in patients with pLN.
Methods
Ninety-eight pLN patients and one hundred controls were enrolled in the study. Serum leptin and adiponectin levels were measured using ELISA. DNA extraction and real-time PCR genotyping were performed for
MTHFR
rs1801131 and
FGG
rs2066865 SNPs.
Results
Compared to healthy controls, pLN patients exhibited significantly greater serum leptin (11.3 vs. 18.2 ng/mL,
p
< 0.001) and adiponectin (18.2 vs. 2.7 ug/mL,
p
< 0.001). Adiponectin levels were positively correlated with proteinuria (
p
< 0.05), while leptin levels positively correlated with proteinuria, SLE disease activity index-2000 (SLEDAI-2K), and cyclophosphamide usage (all
p
< 0.05). There was no significant association between
MTHFR
rs1801131 or
FGG
rs2066865 SNPs and pLN in either codominant or allelic models (all
p
> 0.05). However, the AG genotype of
FGG
gene rs2066865 SNP was significantly associated with high leptin levels (> 15 ng/mL) (
p
= 0.01).
Conclusion
Serum adiponectin and leptin levels are associated with pathological manifestations of pLN. High leptin levels are associated with the AG genotype of
FGG
rs2066865 SNP in pLN patients, suggesting direct involvement in disease progression and potential utility as a disease biomarker.
Introduction: tropomyosin is a pan-allergen that shows cross-reactivity between different species. In tropical countries, allergy to arthropods (mites, shrimp, cockroaches, mosquitoes) or nematodes ...(Ascaris spp) is common. IgE epitopes of tropomyosin may be the source of sensitization and the development of allergic symptoms. However, T epitopes (MHC-II) polarize the Th2 response. Objective: This study aimed to identify by in silico methods tropomyosin consensus B and T epitopes of shrimp species, house dust mites, insects, and nematodes associated with allergic diseases in tropical countries. Methods: in silico analysis included tropomyosin from mites (Der p 10, Der f 10, Blo t 10), insects (Aed a 10, Per a 7, Bla g 7), shrimp (Lit v 1, Pen m 1, Pen a 1), and nematode (Asc l 3); all sequences were taken from the UniProt database. Linear IgE epitopes were predicted with AlgPred 2.0 and validated with BepiPred 3.0. MHC-II binding T cell epitopes were predicted using the IEDB server, which implements nine predictive methods (consensus method, combinatorial library, NN-align-2.3, NN-align-2.2, SMM-align, Sturniolo, NetMHCIIpan -3.1, and NetMHCIIpan -3.2) these predictions focused on 10 HLA-DR and 2 HLA-DQ alleles associated with allergic diseases. Subsequently, consensus B and T epitopes present in all species were identified. Results: we identified 12 sequences that behaved as IgE-epitopes and B-cell epitopes, three of them: 160RKYDEVARKLAMVEA174, 192ELEEELRVVGNNLKSLEVSEEKAN215, 251KEVDRLEDELV261 were consensus in all species. Eleven peptides (T-epitopes) showed strong binding (percentile rank ≤ 2.0) to HLA-DRB1*0301, *0402, *0411, *0701, *1101, *1401, HLA- DQA1*03:01/DQB1*03:02, and HLA- DQA1*05:01/DQB1*02:01. Only two T-epitopes were consensus in all species: 167RKLAMVEADLERAEERAEt GEsKIVELEEELRV199, and 218EEeY KQQIKT LTaKLKEAEARAEFAERSV246. Subsequently, we identified 2 B and T epitope sequences and reached a consensus between species 167RKLAMVEA174 and 192ELEEELRV199. Conclusions: These data describe three sequences that may explain the IgE cross-reactivity between the analyzed species. In addition, the consensus B and T epitopes can be used for further in vitro investigations and may help to design multiple-epitope protein-based immunotherapy for tropomyosin-related allergic diseases.
Objetivo: Este estudio tuvo como objetivo identificar mediante métodos in silico epítopes B y T consenso de tropomiosina de especies de camarón, ácaros del polvo doméstico, insectos y nematodos asociados a enfermedades alérgicas en países tropicales. Métodos: El análisis in silico incluyó tropomiosina de ácaros (Der p 10, Der f 10, Blo t 10), insectos (Aed a 10, Per a 7, Bla g 7), camarones (Lit v 1, Pen m 1, Pen a 1), y nematodo (Asc l 3). Todas las secuencias se tomaron de la base de datos UniProt. Los epítopes IgE lineales se predijeron con AlgPred 2.0 y se validaron con BepiPred 3.0. Los epítopes de células T de unión a MHC-II se predijeron utilizando el servidor IEDB, que implementa nueve métodos predictivos (método de consenso, biblioteca combinatoria, NN-align-2.3, NN-align-2.2, SMM-align, Sturniolo, NetMHCIIpan -3.1 y NetMHCIIpan -3.2). Estas predicciones se centraron en diez alelos HLA-DR y 2 HLA-DQ asociados con enfermedades alérgicas. Posteriormente, se identificaron epítopes consenso B y T presentes en todas las especies. Resultados: Se identificaron 12 secuencias que se comportaron como epítopes de IgE y, también, como epítopes de células B. Tres de ellas: 160RKYDEVARKLAMVEA174, 192ELEEELRVVGNNLKSLEVSEEKAN213 y 251KEVDRLEDELV261, fueron consenso en todas las especies. Once péptidos mostraron una fuerte unión (rango percentil ≤ 2,0) a HLA-DRB1*0301, *0402, *0411, *0701, *1101, *1401 y a HLA HLA-QA1*03:01/DQB1*03:02, o HLA-DQA1*05:01/DQB1*02:01. Solo se encontraron dos secuencias: 167RKLAMVEADLERAEERAEtGEsKIVELEEELRV199 con fuerte afinidad por HLADQA1* 03:01/DQB1*03:02, y HLA-DQA1*05:01/DQB1*02:01. Se identificaron dos secuencias que son epítopos B y T, y son consenso entre especies: 167RKLAMVEA174 y 192ELEEELRV199. Conclusiones: Estos datos describen tres secuencias que pueden explicar la reactividad cruzada de IgE entre las especies analizadas. Además, los epítopos B y T consenso se pueden usar para investigaciones in vitro adicionales, y pueden ayudar a diseñar inmunoterapia basada en proteínas de múltiepítopes para enfermedades alérgicas relacionadas con la tropomiosina.
Introduction: Chronic spontaneous urticaria (CSU) is an inflammatory skin disease related to poor quality of life. Previous studies have found that vitamin D deficiency and vitamin D recep-tor (VDR) ...TaqI, BsmI, FokI, and ApaI gene single-nucleotide polymorphisms (SNPs) influence immune response and susceptibility to skin disorders.
Aim: To explore the role of VDR SNPs, and the association of vitamin D serum levels in a sample of Colombian Caribbean CSU patients.
Methods: It is a case-control study. A group of CSU patients (n = 100) was compared with healthy individuals as a control group (n = 100). VDR polymorphisms were genotyped by quantitative polymerase chain reaction and Taqman® probes. Allelic, genotypic, and haplotype associations were estimated. Serum vitamin D levels were measured using enzyme-linked-immunosorbent serologic assay.
Results: Compared to the control group, the presence of G allele in TaqI and A allele in FokI SNPs of VDR gene was found to be a risk factor for CSU (odds ratio (OR) estimated using logistic regression adjusted by gender: 2.08 and 1.61, respectively, all P values < 0.05). The individuals who carry GCCA haplotype showed decrease in vitamin D levels (11.34 ng/mL; P = 0.002) with the G allele of TaqI and A allele of FokI gene SNPs.
Conclusion: We reported for the first time the association of TaqI rs731236 and FokI rs2228570 VDR gene SNPs showing as a risk factor for CSU in a sample of multiethnic patients from the Colombian Caribbean population.
Pregnancy-associated atypical hemolytic uremic syndrome (P-aHUS) is a rare condition characterized by microangiopathic hemolytic anemia and kidney injury from thrombotic microangiopathy. P-aHUS ...occurs in approximately 1 in 25,000 pregnancies and is strongly related to complement dysregulation and pregnancy-related disorders, such as preeclampsia, eclampsia, and hemolysis, elevated liver enzymes, low platelet (HELLP) syndrome, resulting in adverse perinatal and fetal outcomes. Complement dysregulation in P-aHUS is commonly attributed to genetic mutations or autoantibodies affecting complement factors, including
,
, and
We present a case of a 25-year-old primigravida who experienced severe preeclampsia and HELLP syndrome followed by the development of complicated P-aHUS during the early postpartum period. The patient exhibited severe clinical manifestations, including hypertensive emergency, central nervous system involvement, renal impairment, and microangiopathic hemolytic anemia. Timely initiation of eculizumab therapy resulted in successful disease remission. Further genetic analysis revealed a likely rare pathogenic
gene variant.
Background: Helminth infections for Ascaris lumbricoides and exposure to mite allergens stimulate a Th2 immune response present in allergic diseases. Helminth proteins are well known can modulate the ...host immune response and lessen the inflammation response. We evaluate the Ig E reactivity to a molecule constructed from A. lumbricoides T epitopes (MP1) in sera from patients suffering from T1D, LN, and JIA Methods: We designed and expressed a synthetic multi-epítope protein named MP1 from A. lumbricoides and house dust mites allergens. By indirect ELISA, we evaluated IgE-reactivity to MP1 and to the whole-body extract of Ascaris lumbricoidesin 45 sera from Colombian Caribbean patients with lupus nephritis (LN; n=25), type 1 diabetes (T1D; n=10) and Juvenil idiopathic arthritis (JIA; n=10). Individuals with poly autoimmunity were excluded. All patients were referred to the study by their specialist doctor. Results: IgE to whole-body extract of A. lumbricoides showed the following median concentrations: 484.2 ng/ml (IQR: 203.4) in JIA patients, 325.6 ng/ml (IQR: 179.3) in individuals with LN, and 424.7 ng/ml (IQR: 80.1) in T1D group. On the other hand, IgE-reactivity to MP1 was 126.4 ng/ml (IQR: 90.9) in JIA patients, 130.7 ng/ml (IQR: 94.8) in an individual with LN, and 148.8 ng/ml (IQR: 102.1) in T1D group. Although no statistical differences were observed between patient groups, the IgE to MP1 in all patients (n: 45) (IgE median: 134.2 ng/ml; IQR: 100) were significantly less compared to Ascaris extract (IgE median: 380.7 ng/ml; IQR: 175.8); (W:0.732; p-value: 1.034x10-7). Conclusions: These preliminary results suggest that MP1 showed antigenic properties with low IgE-reactivity compared to Ascaris lumbricoides extract in individuals with autoimmune diseases. Further studies are needed to understand better the immune response induced by this molecule.
Objetivo: Evaluar la reactividad IgE de sueros en pacientes que padecen diabetes tipo 1 (DT1), nefritis lúpica (NL) y artritis idiopática juvenil (AIJ) frente a una molécula construida a partir de epítopes T de alérgenos de A. lumbricoides. Métodos: Se diseñó y expresó una proteína multi-epítopes sintética (MP1), a partir de alérgenos de A. lumbricoides y ácaros del polvo doméstico. Mediante ELISA indirecto, se evaluaron las reactividades IgE anti-MP1 y al extracto de cuerpo entero de Ascaris lumbricoides, en sueros de pacientes con nefritis lúpica (NL; n=25), diabetes tipo 1 (T1D; n=10) y artritis idiopática juvenil (AIJ; n=10), procedentes del Caribe colombiano. Se excluyeron los individuos con poliautoinmunidad. Todos los pacientes fueron remitidos al estudio por su médico especialista. Resultados: La IgE frente al extracto de cuerpo completo de A. lumbricoides mostró concentraciones de 484,2 ng/ml (RIQ: 203,4) en pacientes con AIJ; 325,6 ng/ml (RIQ: 179,3) en individuos con NL; y 424,7 ng/ml (RIQ: 80,1) en el grupo con DT1. Por otra parte, la reactividad de IgE anti-MP1 fue de 126,4 ng/ml (RIQ: 90,9) en los pacientes con AIJ; 130,7 ng/ml (RIQ: 94,8) en los individuos con NL; y 148,8 ng/ml (RIQ: 102,1) en el grupo con DT1. Aunque no se observaron diferencias estadísticas entre los grupos de pacientes, la reactividad IgE anti- MP1 en todos los pacientes (n: 45) (mediana de IgE: 134,2 ng/ml; RIQ: 100), fue significativamente inferior en comparación con el extracto de Ascaris (mediana de IgE: 380,7 ng/ml; RIQ: 175,8); (W: 0,732; p-valor: 1,034x10-7). Conclusiones: Estos resultados preliminares sugieren que MP1 mostró propiedades antigénicas con baja reactividad IgE, en comparación con el extracto de Ascaris lumbricoides en individuos con enfermedades autoinmunes. Se necesitan más estudios para comprender mejor la respuesta inmunitaria inducida por esta molécula.
Introduction
Atypical hemolytic uremic syndrome (aHUS) is a rare and genetically mediated systemic disease most often caused by uncontrolled and chronic complement activation that leads to systemic ...thrombotic microangiopathy, renal and extra-renal damage.
Materials and methods
This is descriptive, retrospective and multicenter study, which reports demographic, clinical, laboratory, and genetic characteristics, as well as their treatment response and outcome of 20 aHUS patients diagnosed between 2014 and 2018.
Results
Most patients were female adults (75%) and 30% were associated to pregnancy/postpartum, 15% to autoimmune disease, and 65% to infections. Gastrointestinal involvement (75%) was the most frequent extra-renal organ damage. Antenatal mortality and mortality rate were 5% and 10%, respectively. 25% of the patients progressed to end-stage renal disease. In 4/8 of patients treated within 1 week of presentation, eculizumab treatment restored multi-organ function after 4 weeks of treatment. CFH (37%) and CFI (25%) mutations were the most frequent.
Conclusion
This is the first series of aHUS cases of Colombian Caribbean region which reports the clinical and epidemiological characteristics of this condition in this region.
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