Report from the Killer-cell Immunoglobulin-like Receptors (KIR) component of the 17th International HLA and Immunogenetics Workshop.

The goals of the KIR component of the 17th International HLA and Immunogenetics Workshop (IHIW) were to encourage and educate researchers to begin analyzing KIR at allelic resolution, and to survey the nature and extent of KIR allelic diversity across human populations. To represent worldwide diversity, we analyzed 1269 individuals from ten populations, focusing on the most polymorphic KIR genes, which express receptors having three immunoglobulin (Ig)-like domains (KIR3DL1/S1, KIR3DL2 and KIR3DL3). We identified 13 novel alleles of KIR3DL1/S1, 13 of KIR3DL2 and 18 of KIR3DL3.

IFNG +874 A/T is associated with acute lymphoblastic leukemia in Mexican Mestizos.

Acute lymphoblastic leukemia (ALL), the most common type of cancer in children worldwide, has one of the highest incidence rates in Mexico. It is a multifactorial disease and different cytokine single nucleotide polymorphisms (SNP), have been associated with ALL expression. Few studies have been published analyzing IFNG +874 T/A and IL2 -330 G/T in this type of leukemia.

Patterns of admixture and population structure in native populations of Northwest North America.

The initial contact of European populations with indigenous populations of the Americas produced diverse admixture processes across North, Central, and South America. Recent studies have examined the genetic structure of indigenous populations of Latin America and the Caribbean and their admixed descendants, reporting on the genomic impact of the history of admixture with colonizing populations of European and African ancestry. However, relatively little genomic research has been conducted on admixture in indigenous North American populations.

HLA-DRB1 Class II antigen level alleles are associated with persistent HPV infection in Mexican women; a pilot study.

Background: Persistent infection with high-risk human papillomavirus (HPV) is a major risk factor for malignant lesions and cervical cancer. A widely studied element in the search for genetic factors influencing risk HPV infection diseases is allelic variation of the human leukocyte antigen (HLA) locus. The study was designed to search for HLA susceptibility alleles contributing to the persistence of HPV infection in Mexican women.

Major histocompatibility complex and strong human leukocyte antigen-DRB1 and gender association with Vogt-Koyanagi-Harada syndrome in Mexican Mestizos.

Vogt-Koyanagi-Harada syndrome (VKH) is a multisystem autoimmune disorder mediated by cytotoxic T cells targeting melanocytes antigen(s). A strong major histocompatibility complex (MHC) association with HLA-DRB1*04:05 has been demonstrated in different populations. We investigated the contribution of HLA-A*, -B*, -C*, -DRB1*, and -DQB1* genes, belonging to the human leukocyte antigen (HLA), to the expression of VKH and we analyzed the influence of gender on the HLA association.

Multiple sclerosis risk markers in HLA-DRA, HLA-C, and IFNG genes are associated with sex-specific childhood leukemia risk.

Previous epidemiologic studies showed four times increased risk of acute lymphoblastic leukemia (ALL) in children of women with multiple sclerosis (MS). MS shows a risk association with Human leukocyte antigens (HLA)-DRA single nucleotide polymorphism (SNP) rs3135388, which is a proxy marker for DRB1*1501. We examined the relevance of rs3135388 in childhood ALL risk along with two other HLA-DRA SNPs in two case-control groups: 114 cases and 388 controls from South Wales (UK) and 100 Mexican Mestizo cases and 253 controls.

HLA complex-linked heat shock protein genes and childhood acute lymphoblastic leukemia susceptibility.

Three heat shock protein 70 (HSP70) genes, HSPA1L, HSPA1A, and HSPA1B, are located within the human leukocyte antigen (HLA) class III region. HSPs act as stress signals and regulate natural killer cell response to cancer. HSP70 gene polymorphisms show disease associations partly due to their linkage disequilibrium with HLA alleles.

Association of narcolepsy-cataplexy with HLA-DRB1 and DQB1 in Mexican patients: a relationship between HLA and gender is suggested.

Background: Narcolepsy-cataplexy is characterized by excessive daytime sleepiness with recurrent episodes of irresistible sleep, cataplexy, hallucinations and sleep paralysis. Its aetiology is unknown, but it is positively associated with the human leukocyte antigens (HLA) in all studied populations. The purpose of the present study was to investigate the association of HLA class II DRB1/DQB1 alleles with narcolepsy-cataplexy in Mexican Mestizo patients.

Phenotype frequencies of autosomal minor histocompatibility antigens display significant differences among populations.

Minor histocompatibility (H) antigens are allogeneic target molecules having significant roles in alloimmune responses after human leukocyte antigen-matched solid organ and stem cell transplantation (SCT). Minor H antigens are instrumental in the processes of transplant rejection, graft-versus-host disease, and in the curative graft-versus-tumor effect of SCT. The latter characteristic enabled the current application of selected minor H antigens in clinical immunotherapeutic SCT protocols.

Distribution of HLA-B27 subtypes in ankylosing spondylitis in an Israeli population.

Background: The aim of this study was to investigate the contribution of the B27 subtypes to ankylosing spondylitis (AS) expression in a group of Jewish patients from Israel and to compare their distribution with that found in Mexican Mestizo patients. Several HLA-B27 alleles have been clearly associated with AS. Among them, B( *)2705 and B( *)2702 are involved in susceptibility in different populations worldwide.

Magnetic fields and acute leukemia in children with Down syndrome.

Background: : We analyzed effects of exposure to magnetic fields on the expression of acute leukemia in children with Down syndrome (who have a 20-fold higher risk of leukemia).

Methods: : We performed a case-control study that included 42 children with both acute leukemia and Down syndrome as cases and 124 healthy children with Down syndrome as controls. We obtained demographic information concerning the children and took spot measurements of magnetic fields at each residence.

HLA and autoimmune diseases: Type 1 diabetes (T1D) as an example.

Autoimmune diseases need to be considered at a genetic and mechanistic level. T1D is an autoimmune, chronic, multifactorial and polygenic disease characterized by the destruction of the pancreatic beta-cells associated with long term dysfunction of several organs and tissues. Mechanisms of susceptibility include epi-genetic and post-transcriptional effects that regulate transmission and expression of the inherited genes.

Hematopoietic stem cell transplantation (HSCT): an approach to autoimmunity.

HSCT provides the opportunity to replace a damaged tissue. It is the most important treatment for high risk hematologic malignant and non malignant disorders. An important challenge in the identification of matched donors/patients is the HLA diversity.

HPV16-specific cytotoxic T lymphocyte responses are detected in all HPV16-positive cervical cancer patients.

Objectives: The specific CTL response against human papillomavirus (HPV) antigens in women with cervical cancer has been poorly studied. Immunological monitoring of this response is central for understanding the principles that underlie successful immunotherapeutic strategies. The aim of the study was to investigate the HPV16 E6/E7-specific CTL immune response in a group of untreated HPV16-positive cervical cancer patients.

Role of HLA class II alleles in susceptibility to and protection from localized cutaneous leishmaniasis.

Localized cutaneous leishmaniasis (LCL) is the prevalent form of leishmaniasis in Mexico. It is limited to the skin; reversible upon treatment and the host cellular immune response is intact. Several genes that influence the expression of LCL have been described in the mouse.

Molecular mechanisms of MHC linked susceptibility in leprosy: towards the development of synthetic vaccines.

Tuberculoid (TT) and lepromatous leprosy (LL) develop in the human host depending on his ability to trigger a specific cellular immune response(CIR). Different genes have been demonstrated in susceptibility/protection and may explain the forms of leprosy. The major histocompatibility complex (MHC) play an important role.

Classic Pars Planitis: strong correlation of class II genes with gender and some clinical features in Mexican Mestizos.

The purpose of this study was the investigation of human leukocyte antigen (HLA) genes in Mexicans with classical Pars Planitis (CPP). Seventy-nine unrelated patients and 204 healthy controls were studied. HLA-A, -B, and -C typing was done on T cells isolated with immunomagnetic beads.

Native American mtDNA prehistory in the American Southwest.

This study examines the mtDNA diversity of the proposed descendants of the multiethnic Hohokam and Anasazi cultural traditions, as well as Uto-Aztecan and Southern-Athapaskan groups, to investigate hypothesized migrations associated with the Southwest region. The mtDNA haplogroups of 117 Native Americans from southwestern North America were determined. The hypervariable segment I (HVSI) portion of the control region of 53 of these individuals was sequenced, and the within-haplogroup diversity of 18 Native American populations from North, Central, and South America was analyzed.

Protective effect of DRB1 locus against type 2 diabetes mellitus in Mexican Mestizos.

The aim of the study was to investigate the participation of human leukocyte antigen (HLA) class II alleles in the expression of type 2 diabetic and in nondiabetic subjects with and without family history of diabetes. The purpose was to evaluate any HLA association and to look for different patterns of insulin resistance and insulin secretion, comparing subjects with a low probability of developing diabetes, as a result of their family history. We recruited 87 healthy subjects without family history of diabetes, 48 healthy subjects with family history, and 47 type 2 diabetic patients.

Frequency of cytokine polymorphisms in populations from western Europe, Africa, Asia, the Middle East and South America.

PCR-SSOP identification procedures for IL-2, IL-6, IL-10, TNF-alpha and TNF-beta cytokine polymorphisms have been developed. Application of the procedures to a range of diverse geographically distributed populations has identified ethnic differences within the groups studied. Five populations were investigated, Northern Ireland, South African Zulu, Omani, Singapore Chinese and Mexican Mestizos.