NKG2D Polymorphism in Melanoma Patients from Southeastern Spain.

BACKGROUND: Natural killer (NK) and CD8+ T cells are involved in the immune response against melanoma. C-Type lectin-like NK cell receptors are located in the Natural Killer Complex (NKC) region 12p13.2-p12.3 and play a critical role in regulating the activity of NK and CD8+ T cells. An association between polymorphisms in the NKC region, including the NKG2D gene and NKG2A promoter, and the risk of cancer has been previously described. The aim of this study was to analyze the association of polymorphisms in the NKC region with cutaneous melanoma in patients from southeastern Spain. METHODS: Seven single-nucleotide polymorphisms (SNPs) in the NKG2D gene (NKC3,4,7,9,10,11,12), and one SNP in the NKG2A promoter (NKC17) were genotyped by a TaqMan 5' Nuclease Assay in 233 melanoma patients and 200 matched healthy controls. RESULTS: A linkage disequilibrium analysis of the SNPs performed in the NKC region revealed two blocks of haplotypes (Hb-1 and Hb-2) with 14 and seven different haplotype subtypes, respectively. The third most frequent haplotype from the block Hb-2-NK3 (CAT haplotype)-was significantly more frequent on melanoma patients than on healthy controls (p = 0.00009, Pc = 0.0006). No further associations were found when NKC SNPs were considered independently. CONCLUSIONS: Our results suggest an association between NKG2D polymorphisms and the risk of cutaneous malignant melanoma.

Dens invaginatus: reporte de un caso clínico / Dens invaginatus: case report

RESUMEN Introducción: De las malformaciones dentales una de las más frecuentes es el dens in vaginatus o dens in dente, esta alteración anatómica representa un reto para el clínico, debido a su anatomía compleja; sin embargo, gracias a los auxiliares de diagnóstico como la tomografía cone-beam, podremos planear el tratamiento para ofrecer el mejor pronóstico. El presente artículo relata un caso clínico de dens in dente presente en diente veintiuno, con necrosis pulpar y periodontitis apical asintomática. Se solicitó TAC cone-beam, se diagnosticó como tipo II según Oehlers; es instrumentado, irrigado con ultrasonido y obturado con técnica «onda continua de calor¼, con un éxito radiográfi co a seis meses de evolución. Actualmente, gracias a los métodos de diagnóstico y auxiliares de tratamiento tales como el ultrasonido, los sistemas de inyección de gutapercha, se pueden ofrecer tratamientos más efi cientes en la terapéutica endodóncica.

ABSTRACT Introduction: The Dens Invaginatus or Dens in dent it is the most common dental abnormal structure, this anatomic variation means a true clinic challenge because of its complex anatomy, however , thanks to the auxiliary tools for diagnosis just like Cone Beam Computerized Tomography, we can plan a good treatment to offer the best diagnosis. This article describes a clinic case about Dens in Dent in twenty one tooth with pulp necrosis and asymptomatic apical periodontitis. Cone Beam Computerized Tomography was requested, the image helped to classify the kind of Dens in Dent which is type II according to Oehlers´s classifi cation. It is instrumented, irrigated with ultrasound and sealed with "continuous wave of heat "technique. This technique ensures a radiographic success with six months of evolution. Currently, thanks to diagnostic methods and treatment aids such as ultrasound, gutta-percha injection system more effi cient treatments can be offered in endodontic therapeutics.

MHC class I chain-related gene a diversity in patients with cutaneous malignant melanoma from southeastern Spain.

A limited number of studies have been performed so far on the polymorphism in the transmembrane region (exon 5) of the major histocompatibility complex class I chain-related gene A (MICA) in patients with melanoma. However, the influence of MICA polymorphism in extracellular domains (exons 2, 3, and 4) has not been investigated on melanoma disease. This study aims to characterize the influence of extracellular MICA polymorphism, and its previously described linkage disequilibrium with HLA-B locus, on patients with cutaneous melanoma from southeastern Spain. For this purpose, MICA and HLA-B genotyping was performed in 233 patients and 200 ethnically matched controls by luminex technology. Patients were classified according to the presence of methionine or valine at codon 129 of MICA gene. We found a high frequency of MICA(*)009 in melanoma patients compared with controls (P = 0.002, Pc = 0.03). Our results also showed an association between MICA(*)009 and HLA-B(*)51 alleles in both patients and controls. This association was stronger in patients than controls (P = 0.015). However, a multivariate logistic regression model showed that neither MICA(*)009 nor the combination MICA(*)009/HLA-B(*)51 was associated with melanoma susceptibility. No relationship was observed between MICA-129 dimorphism and melanoma nor when MICA polymorphism was evaluated according to clinical findings at diagnosis.

Immunogenetic biomarkers in inflammatory bowel diseases: role of the IBD3 region.

Many studies have demonstrated the linkage between the IBD3 region (6p21.1-23), an area which encompasses the famous human leukocyte antigen (HLA) complex, and Crohn's disease (CD) or ulcerative colitis (UC). IBD3 is the only region that meets genome-wide significance, and provides stronger evidence of the linkage than 16p13.1-16q12.2 (IBD1), the locus that contains the susceptibility gene CARD15. However, despite these findings, IBD3 susceptibility genes remain elusive and unclear due to the strong linkage disequilibrium, extensive polymorphism, and high gene density that characterize this area and also due to varying allele frequencies in populations around the world. This area presents an extremely high abundance of genes, including the classical and non-classical major histocompatibility complex (MHC) class I and II genes, and other genes, namely MHC class III genes tumor necrosis factor (TNF)-α and -ß, and Hsp, whose proteins play key functions in immunological processes. To date, it is not clear which genes within the MHC family contribute to the IBD pathogenesis, although certain HLA alleles have been associated with IBD. Recent insights into the biological function of other genes encoded within the IBD3 region, such as the MHC class I chain-related (MIC) genes, have led investigators to a more comprehensive exploration of this region. MHC class I chain-related molecule A (MICA) is highly polymorphic and interacts with NKG2D, its receptor on the surface of NK, Tγδ and T CD8(+) cells. Increased expression of MICA in intestinal epithelial cells and increased expression of NKG2D in CD4(+) T cells (lamina propria) in patients with CD have also been reported. MICA alleles have also been associated with IBD, and a variation at amino acid position 129 of the α2-heavy chain domain seems to categorize MICA alleles into strong and weak binders of NKG2D receptor, thereby influencing the effector cells' function. In this regard, a relevant role of MICA-129-Val/Met single nucleotide polymorphism has recently been implicated in the pathogenesis of IBD. TNF-α and -ß also play an important role in inflammatory response. In fact, IBD is commonly treated with TNF-α inhibitors. Additionally, polymorphisms of TNF-α gene are known to affect the gene expression level and particular TNF-α genotypes may influence the response of IBD patients treated with TNF-α inhibitors.

HLA-DRB1 and HLA-DQB1 genes on susceptibility to and protection from allergic bronchopulmonary aspergillosis in patients with cystic fibrosis.

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity pulmonary disease that affects both patients with cystic fibrosis (CF) and those with asthma. HLA-DRB1 alleles have previously been associated with ABPA-CF susceptibility; however, HLA-DQB1 allele associations have not been clearly established. The aim of the present study was to investigate HLA class II associations in patients with ABPA-CF and determine their roles in susceptibility or protection. Patients with ABPA-CF, patients with CF without ABPA, patients with asthma without ABPA (AST), and healthy controls were included in this study. DNA was extracted by automatic extractor. HLA-DRB1 and -DQB1 genotyping was performed by the Luminex PCR-SSOP method (One Lambda, Canoga Park, CA, USA). Allele specific PCR-SSP was also performed by high-resolution analysis (One Lambda). Statistical analysis was performed with SSPS and Arlequin software. Both HLA-DRB1*5:01 and -DRB1*11:04 alleles occurred with greater frequency in patients with ABPA-CF than in those with AST and CF and control subjects, corroborating previously published data. On the other hand, analysis of haplotypes revealed that almost all patients with ABPA-CF lacking DRB1*15:01 or DRB1*11:04 carry either DRB1*04, DRB1*11:01, or DRB1*07:01 alleles. In the HLA-DQB1 region, the HLA-DQB1*06:02 allele occurred more frequently in patients with ABPA-CF than in those with AST and CF and healthy controls, whereas HLA-DQB1*02:01 occurred less frequently in patients with ABPA-CF. These data confirm that there is a correlation between HLA-DRB1*15:01, -DRB1*11:04, DRB1*11:01, -DRB1*04 and -DRB1*07:01 alleles and ABPA-CF susceptibility and suggest that HLA-DQB1*02:01 is an ABPA-CF resistance allele.

Low median fluorescence intensity could be a nonsafety concept of immunologic risk evaluation in patients with shared molecular eplets in kidney transplantation.

Human leukocyte antigen (HLA) antibodies are usually "epitope" and not "antigen" specific. This work presents an interesting case concerning Luminex median fluorescence intensity (MFI) levels in antibodies considered low risk (<1,000), but producing humoral rejection. These low-titer antibodies could play an important role in transplantation. A 42-year-old woman was retransplanted with a deceased donor with negative complement-dependent cytotoxicity cross-matching. Our patient was pretransplant (PrT) sensitized to HLA antigens (single antigens (SA) = 31%) for 1 previous transplant. Thus, the formerly detected sensitized antigens were A32, A30, A31, cross-reacting group 5C, and DQ3 with a MFI(max) ≈ 4,127. In the posttransplantation period (PTP), the patient exhibited important instability in renal function and we detected an increased SA percentage (61%) with MFI(max) = 15,029 (A*32) with other antigens (detected with a low PrT MFI [<1,000]) as anti-A*03 (MFI(max) = 13,301) and anti-A*11 (MFI(max) = 13,714) specificities. Anti-A*03 was a donor-specific antibody (DSA). Renal biopsy was compatible with humoral rejection. The patient was pulsed with methylprednisolone, plasmapheresis, and intravenous immunoglobulin without improvement. Thus, we added anti-CD20 and the initial clinical response was highly favorable. Biopsies resulted in suggestive rejection reversion. MFI A*03 DSA decreased to 6,908 and later to MFI(max) = 5,505. After a 6-month PTP, the patient is well with MFI(max) = 3,124. It was possible to define exactly the potential immunizing epitope eplets whose recognition determined the specific antibody production. A*32:01, A*30:01, A*31:01 (detected PrT), A*11:01, and A*03:01 (detected PTP) alleles have several shared eplets (62QE, 70AQS, and 76VGT), with 62QE being the only eplet present on all alleles. In conclusion, low MFI levels in antibodies considered low risk could be important in posttransplant humoral rejection, although the patient's renal function can be restored. Thus, specific shared eplets should always be investigated with respect to previous transplant mismatches.