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  • Nonmyeloablative HLA-Matched Sibling Allogeneic Hematopoietic Stem Cell Transplantation for Severe Sickle Cell Phenotype

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    JAMA. 2014; 312(1):48-56. doi: 10.1001/jama.2014.7192

    In a trial involving 30 adult patients with sickle cell phenotype with or without thalassemia, Hsieh and coauthors report that after undergoing nonmyeloablative allogeneic hematopoietic stem cell transplantation from human leukocyte antigen–matched siblings, 26 patients achieved long-term engraftment.

  • Hydrolyzed Infant Formula and Early β-Cell Autoimmunity: A Randomized Clinical Trial

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    JAMA. 2014; 311(22):2279-2287. doi: 10.1001/jama.2014.5610

    In a double-blind randomized clinical trial of 2159 infants with HLA-conferred disease susceptibility and a first-degree relative with type 1 diabetes, The TRIGR Study Group tests the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of diabetes-associated autoantibodies, May 2002-April 2013 at 78 study centers in 15 countries.

  • JAMA October 12, 2011

    Figure 2: Antigen Presentation and Production of Antibodies to Gluten Peptides and Tissue Transglutaminase (tTG)

    In the subepithelium of the small intestine, native (partially digested) gluten peptides are deamidated by the enzyme tTG. While tTG is ubiquitous, it is predominantly stored intracellularly in an inactive state and released in the presence of inflammation and activated by higher levels of extracellular calcium ions. Deamidation leads to change in shape and charge of the gluten peptides, permitting high-affinity binding to HLA-DQ2 and -DQ8 on APCs such as dendritic cells and macrophages. Only HLA-DQ2 and -DQ8 are able to bind gluten peptides strongly enough to trigger an inflammatory reaction, so the presence of at least 1 of these molecules is a prerequisite for development of celiac disease. Naive T cells that have been activated by deamidated gluten presented by APCs are then able to stimulate both a TH1 cytotoxic and TH2 humoral antibody response. The TH2 response leads to production of antibodies against native gluten peptide, deamidated gluten peptide, and tTG. Antibodies to the self-protein tTG are produced because tTG is often still complexed with deamidated gluten peptides during presentation by APCs. This directed anti-self immune response is the major autoimmune component of celiac disease. TCR indicates T-cell receptor; IFN, interferon.
  • The Next Frontier for Stem Cell Transplantation: Finding a Donor for All

    Abstract Full Text
    JAMA. 2010; 303(14):1421-1422. doi: 10.1001/jama.2010.413
  • JAMA December 16, 2009

    Figure: Cord Blood Transplants

    Taking into account exposure of a fetus to maternal human leukocyte antigens that the fetus itself does not inherit might improve the success of cord blood stem cell transplants.
  • JAMA February 1, 2006

    Figure: Survival of Patients With SCID Who Received a Bone Marrow Transplant From a RID, MUD, or MMRD

    For patients who received multiple transplants, survival was calculated from the date of the last transplantation. RID indicates family-related, HLA-identical donor; MUD, HLA-matched unrelated donors; and MMRD, HLA-mismatched related donor.
  • Bone Marrow Transplantation for Severe Combined Immune Deficiency

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    JAMA. 2006; 295(5):508-518. doi: 10.1001/jama.295.5.508
  • Clinical Results From Transplanting Incompatible Live Kidney Donor/Recipient Pairs Using Kidney Paired Donation

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    JAMA. 2005; 294(13):1655-1663. doi: 10.1001/jama.294.13.1655
  • Kidney Paired Donation and Optimizing the Use of Live Donor Organs

    Abstract Full Text
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    JAMA. 2005; 293(15):1883-1890. doi: 10.1001/jama.293.15.1883
  • JAMA July 7, 2004

    Figure: Endometrial Cells Derived From Donor Stem Cells in Bone Marrow Transplant Recipients

    Immunohistochemistry for HLA-A11 using anti–HLA-A11 monoclonal antibody, biotin peroxidase detection system, and diaminobenzidine as the chromogen (brown), and for leukocyte common antigen (CD45) using anti-CD45 monoclonal antibody, biotin peroxidase detection system, and Nova red as the chromogen (red). Hematoxylin was used as the counterstain. A, Control showing concordant HLA-A11–positive epithelial cells (brown) and CD45-positive leukocytes (brown and red) in a nontransplanted individual (original magnification ×200). B, Endometrial glands of HLA-A11–positive donor origin (brown) in HLA-A11–negative transplant recipient (patient 1) and surrounding leukocytes (red). C, Endometrial stromal cells in HLA-A11–negative transplant recipient (patient 1) showing endogenous stromal cells (HLA-A11 negative/CD45 negative; blue [small arrow]); stromal cells of HLA-A11–positive donor origin (HLA-A11 positive/CD45 negative; brown [black arrowhead]); and leukocytes of donor origin (HLA-A11 positive/CD45 positive; brown and red [white arrowhead]) (original magnification ×400).
  • JAMA July 7, 2004

    Figure: Endometrial Cells Derived From Donor Stem Cells in Bone Marrow Transplant Recipients

    Lane A, Molecular weight markers. Lane B, Positive control (actin). Lanes C-G show RT-PCR amplification products using HLA-A11 exon 3 primers and varying other components: lane C, reverse transcriptase and no endometrial RNA; lane D, reverse transcriptase and endometrial RNA from an HLA-A11–negative control; lane E, no reverse transcriptase and endometrial RNA from an HLA-A11–positive control; lane F, reverse transcriptase and endometrial RNA from an HLA-A11–negative transplant recipient (patient 1) who received HLA-A11–positive bone marrow; and lane G, reverse transcriptase and endometrial RNA from an HLA-A11–positive control.
  • JAMA July 7, 2004

    Figure: Endometrial Cells Derived From Donor Stem Cells in Bone Marrow Transplant Recipients

    Immunohistochemistry using anti–HLA-A11 monoclonal antibody, biotin peroxidase detection system, diaminobenzidine as the chromogen (brown), and hematoxylin counterstain. A, HLA-A11–negative control (original magnification ×200). B, HLA-A11 immunopositivity (brown) in an HLA-A11–positive control (original magnification ×200). C, HLA-A11 immunopositivity (brown) in patient 1. More than 50% of the cells were of donor origin (original magnification ×100). D, Endometrial glands partially derived from cells of donor origin (brown; original magnification ×400). E, Rare cells of donor origin (brown) in an endometrial gland. Functional differentiation is noted by characteristic cilia. Arrowheads identify the ciliated epithelial surface (original magnification ×600).
  • JAMA July 7, 2004

    Figure: Endometrial Cells Derived From Donor Stem Cells in Bone Marrow Transplant Recipients

    Immunofluorescence using tetrarhodamine isothiocyanate for calcitonin expression (red) and fluorescein isothiocyanate for donor-derived cells (green) in endometrial epithelial cells of HLA-A11–negative transplant recipient (patient 1) who received bone marrow from an HLA-A11–positive donor. A, Calcitonin expression in endometrial epithelium indicative of receptivity to blastocyst implantation. B, Mismatched HLA-A11–positive endometrial epithelial cell of donor origin (arrowheads). C, Merge demonstrating HLA-mismatched cell expressing calcitonin as a marker of functional differentiation (original magnification ×100).
  • Endometrial Cells Derived From Donor Stem Cells in Bone Marrow Transplant Recipients

    Abstract Full Text
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    JAMA. 2004; 292(1):81-85. doi: 10.1001/jama.292.1.81
  • JAMA May 5, 2004

    Figure 1: Set of Polymorphic STR Markers in HLA Region of Chromosome 6 Used for Preimplantation HLA Typing

    Graphic representation of short tandem repeats (STRs) in HLA classes I, II, and III on chromosome 6. All STR markers are dinucleotide repeats (AC)n, except for DQCARII, which is (CTG)n; TNF b,c,d—(CT)n; 62—(TC-CA)n; MICA—(GCT)n; D6S510—(CA-GA)n; MOG d—(CTC)n. The STRs needed for identification of matching are shown in relation to genes in the HLA region, ordered from telomere (top) to centromere (bottom), allowing accurate HLA typing and identification of possible recombinations, which may lead to misdiagnosis. Markers with asterisks indicate possible ambiguity in localization.
  • JAMA May 5, 2004

    Figure 3: Preimplantation HLA Typing for Diamond-Blackfan Anemia, Resulting in Birth of an HLA-Matched Child

    Short tandem repeat (STR) and gene order for haplotypes of mother, father, and affected child. Examples of different results of HLA typing of biopsied blastomeres are shown. Embryo 1 is HLA matched to the affected sibling. Embryo 8 shows maternal recombination and embryo 16 shows double recombination involving both the paternal and maternal alleles. Embryo 5 shows an extra maternal chromosome consistent with trisomy 6. Markers with asterisks indicate possible ambiguity in localization. Genes with asterisks indicate allelic variants.
  • JAMA May 5, 2004

    Figure 4: Preimplantation HLA Typing for Acute Lymphoid Leukemia, Resulting in Birth of an HLA-Matched Child

    Short tandem repeat (STR) order for haplotypes of mother, father, and affected child. Examples of different results of HLA typing of biopsied blastomeres are shown. Embryo 4 is HLA matched to the affected sibling. Embryo 1 has no paternal chromosome present (monosomy 6). Embryo 2 shows only maternal chromosomes being present (uniparental disomy). Embryo 7 is both a paternal and maternal nonmatch, the latter being due to maternal recombination. The other 2 embryos are nonmatches, embryo 5 being a maternal match only and embryo 6 being a paternal match only. Markers with asterisks indicate possible ambiguity in localization.
  • Preimplantation HLA Testing

    Abstract Full Text
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    JAMA. 2004; 291(17):2079-2085. doi: 10.1001/jama.291.17.2079
  • JAMA October 1, 2003

    Figure: Infant Diet Exposures by HLA-Defined Risk

    A, Proportion becoming positive for islet autoimmunity by age at first exposure to any cereals in all 1183 children. B, Proportion becoming positive for islet autoimmunity by age at first exposure to any cereals in 321 children who are HLA positive. C, Proportion becoming positive for islet autoimmunity by age at first exposure to any cereals in 862 children who are negative.
  • Timing of Initial Cereal Exposure in Infancy and Risk of Islet Autoimmunity

    Abstract Full Text
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    JAMA. 2003; 290(13):1713-1720. doi: 10.1001/jama.290.13.1713