HLA haplotypes

Tumor cells in the first metastasis escaped immune recognition due to selective loss of HLA haplotype, but maintain the expression of HLA-A2 antigen. In contrast, in the second metastasis immune escape from immune dominant antigen-specific T cell responses were mediated by HLA class I downregulation which results in the impaired presentation of this epitope, whereas another tumor antigen-specific epitope was presented. This resulted in the shift of the dominant T cell response to a subdominant targeted response. 

Jimenez, P., Canton, J., Collado, A., Cabrera, T., Serrano, A., Real, L. M., Garcia, A., Ruiz-Cabello, F., and Garrido, F., 1999, Chromosome loss is the most frequent mechanism contributing to HLA haplotype loss in human tumors, Int J. Cancer 83 91-77. 

Maleno, L, Lopez Nevot, M. A., Seliger, B., and Garrido, F., 2004, Low frequency of HLA haplotype loss associated with loss of heterozygocity in chromosome region 6p21 in clear renal cell carcinomas, Int J. Cancer 109 636-638. 

IDDM is associated with other diseases thought to involve autoimmune components (4) activated cell-mediated immunity toward pancreatic islet cells and cell antigens from IDDM patients and (5) the correlation of IDDM with HLA haplotypes associated with other autoimmune diseases (Maclaren, 1981 Lern-marketal., 1991 Andreani et al., 1991 Rossini etal., 1991). 

A 32-year-old woman with previous autoimmune disorders and a susceptible HLA haplotype developed diabetes with newly positive glutamic acid decarboxylase... 

Ross OA, Curran MD, Rea IM, Hyland P, Duggan O, Barnett CR, Annett K, Patterson C, Barnett YA, Middleton D. HLA haplotypes and TNF polymorphism do not associate with longevity in the Irish. Mech Agein Dev 2003 124 563-567. 

Usuku K, Sonoda S, Osame M, Yashiki S, Takahashi K, Matsumoto M, Sawada T, Tsuji K, Tara M, Igata A (1988) HLA haplotype-linked high immune responsiveness against HTLV-I in HTLV-I-associated myelopathy Comparison with adult T-ceU leukemia/lymphoma. Ann Neurol 23(Suppl) S 143-150. 

Skin reactions have a general incidence of 10%, are more common in patients with renal disorders and in those taking thiazide diuretics, and are closely correlated with persistently high serum concentrations of oxipurinol (13). The positive association of severe skin reactions with HLA haplotypes AW33 and B17 suggests a genetic predisposition to these reactions (14). 

Treatment with sulfasalazine was associated with lupus-Uke symptoms and systemic lupus eiythematosus-related autoantibody production in 10% of patients with early rheumatoid arthritis risk factors included a systemic lupus eiythematosus-related HLA haplotype, increased serum interleukin-10 concentrations, and a speckled pattern of antinuclear antibodies (96). 

One was a known case of pre-existent multiple sclerosis but the other had no history of neurological diseases. Both had HLA haplotype DR2 and B7, which are associated with multiple sclerosis. A causal link between immunization and demyelination cannot be established from these two case reports, but the time interval would fit a proposed immunological mechanism. In addition, the Centers for Disease Control (CDC) in Atlanta, Georgia, received reports on four cases of chronic demyelinating disease. Several other reports describe related conditions or other forms of neurological disorder. 

Isolated reports of Candida esophagitis or Pneumocystis proved Pneumocystis carinii) infections in immunocompetent patients and the possible decrease in CD4-I- T cells with or without opportunistic infections in several HIV-infected patients (SED-13,1097) (379) suggest that unexpected immunosuppressive effects of interferon alfa can occur. An autoimmune destruction of CD4 cells in patients with a particular HLA haplotype has been proposed as a possible mechanism (380). One patient also had an acute and fatal acute precipitation of infection with Entamoeba histolytica (SEDA-22, 403). However, the available evidence is still very limited and no firm conclusion can be drawn on a possible association between interferon alfa treatment and a fall in CD4 cell count or an immunosuppressive effect. 

From reports containing information on HLA types, clinical descriptions of adverse events in those given Lyme disease vaccine are similar in people with DR4 and non-DR4 HLA haplotypes and do not suggest more inflammatory arthritis in people of DR4 haplotype (15) [http //www.fda.gOv/ohrms/dockets/ac/01/briefing/3680b2-06.pdf]. The characteristics of adverse events in people with a self-reported history of Lyme disease do not differ substantially from all adverse events after Lyme... 

As exemplified by HLA-DQp haplotypes in type I diabetes mellitus, an individual s HLA status may be relevant to genetic counseling for certain multifactorial diseases. The relation of HLA haplotypes to disease and the use of this information in genetic counseling are referred to as... 

Fig. 6. Inheritance of HLA haplotypes, Either one of the father s haplotypes can combine with either one of the mother s haplotypes, resulting in four haplotypic combinations in the offspring.

Fig. 7. Meiotic recombination affecting HLA haplotypes. The offspring has inherited an intact A3, B44, DR4 haplotype from the father and a recombinant haplotype from the mother consisting of A2 and B13 from one chromosome and OR5 from the other.

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