Spurious elevation of hemoglobin A1c by hereditary persistence of fetal hemoglobin.

We present the case of a 61- year-old black woman with a diagnosis of type 2 diabetes and a falsely elevated hemoglobin A1c (HbA1c) due to hereditary persistence of fetal hemoglobin. Physicians and allied health care professionals are alerted to this potentially significant problem in the diagnosis and management of diabetes mellitus (DM), particularly in the wake of the Diabetes Complications and Control Trial when "strict" glycemic control assessed by HbA1c is now the standard of care.

Sporadic Creutzfeldt-Jakob disease presenting as major depression.

We describe a 68-year-old white woman who initially had symptoms of major depression and was admitted to a psychiatric hospital where she had electroconvulsive therapy. With failure of psychiatric treatment and subsequent rapidly progressive dementia, she had left frontal brain biopsy. The biopsy revealed spongiform changes, the hallmark of Creutzfeldt-Jakob disease (CJD). We report a case of sporadic CJD with unusual initial presentation of psychiatric symptoms.

Bronchiolitis obliterans with organizing pneumonia (BOOP) heralding anti-Jo-1-positive polymyositis.

We report a 51-year-old man who presented with 3 weeks of polyarthritis with fever, nonproductive cough, bibasilar crackles, tachypnea, and hypoxia. Initial laboratory data showed an increased erythrocyte sedimentation rate, rheumatoid factor, and anti-Jo-1 antibody. Imaging studies showed bilateral lower lobe infiltrates of the lung. A transbronchial biopsy specimen revealed characteristic findings for bronchiolitis obliterans organizing pneumonia (BOOP). About 6 months later, he developed profound proximal muscle weakness with a dramatic increase in creatine phosphokinase and aldolase and a further elevation of anti-Jo-1. Muscle biopsy specimen findings were consistent with polymyositis.This represents an unusual case in which BOOP occurred at the onset of an illness initially suggestive of rheumatoid arthritis (RA). The anti-Jo-1-positivity led to close follow up and later discovery of evolution into polymyositis. BOOP can be an early feature of polymyositis as well as RA.

Characterization of a conserved T cell epitope in HIV-1 gp41 recognized by vaccine-induced human cytolytic T cells.

A human CTL epitope located in a region of the HIV-1 envelope protein gp41 that is highly conserved among various HIV-1 strains was identified. This epitope was recognized by CD4+ CTL clones that were induced in seronegative humans by immunization with recombinant gp160. Fusion proteins carrying portions of the HIV-1 env gene and synthetic peptides were used to localize this epitope to amino acids 584-595 of the HIV-1 BRU env sequence. Only two positions within this epitope showed variation among North American HIV-1 isolates, and the substitutions were conservative in nature. The Lys to Arg substitution at position 593 abolished recognition, probably by interfering with the peptide-MHC interactions. This epitope was recognized in association with at least one subtype of the widely distributed human class II MHC specificity DPw4, namely DPw4.2. The relatively high frequency of this allele (27.2% among Caucasians) makes it likely that a larger fraction of the population would generate a response directed at this epitope than would be the case for epitopes recognized in the context of gene products of most other class II and class I loci. Interestingly, the closely related DP beta-chain allele types 4.1 and 2.1, which differ from 4.2 by 3 and 1 amino acids, respectively, were unable to present this gp41 peptide to DPw4.2-restricted clones. Comparison of the structure of this epitope with that of other peptides recognized in the context of DPw4.2 led to the identification of a consensus sequence for DPw4.2 binding peptides. Because the gp41 CTL epitope 584-595 identified here is highly conserved and is recognized in the context of a common DP allele, it may represent an important target region for vaccine development. Our results indicate that vaccines containing this epitope may induce in a significant fraction of those immunized CTL active against at least half of all HIV-1 strains.

Induction of CD4+ human cytolytic T cells specific for HIV-infected cells by a gp160 subunit vaccine.

Cytolytic T lymphocyte (CTL) responses were evaluated in humans immunized with recombinant human immunodeficiency virus type 1 (HIV) envelope glycoprotein gp160. Some vaccinees had gp160-specific CTLs that were shown by cloning to be CD4+. Although induced by exogenous antigen, most gp160-specific CTL clones also recognized gp160 synthesized endogenously in target cells. These clones lysed autologous CD4+ T lymphoblasts infected with HIV. Of particular interest were certain vaccine-induced clones that lysed HIV-infected cells, recognized gp160 from diverse HIV isolates, and did not participate in "innocent bystander" killing of noninfected CD4+ T cells that had bound gp120.

Genetic variability in HIV-1 gp120 affects interactions with HLA molecules and T cell receptor.

The propensity of HIV-1 to undergo sequence variation, particularly in the envelope glycoprotein gp120, complicates vaccine development and may enable the virus to evade ongoing immune responses in infected individuals. We present here a molecular analysis of the effects of this variability on human T cell recognition of HIV-1 gp120. Synthetic peptides representing a defined CD4+ human T cell epitope in gp120 were used to survey gp120 molecules from various HIV-1 strains for the capacity to be recognized in the context of a single human MHC molecule, DR4. Variation affected recognition at two levels. For some strains, variation in this epitope was sufficient to alter the interaction of Ag receptors on gp120-specific human T cell clones with peptide-DR4 complexes on APC. In the case of two strains, the natural variation was sufficient to prevent the critical initial interaction between the relevant gp120 peptides and DR4 on the APC. However, these strains were highly divergent from the reference strain. Thus it is encouraging to note that the range of natural sequence variation in this T cell epitope falls, for the most part, within the range of peptide sequences that can be accommodated by the relevant human MHC molecule.

Anchor sequence-dependent endogenous processing of human immunodeficiency virus 1 envelope glycoprotein gp160 for CD4+ T cell recognition.

Human CD4+ T cell clones and cell lines were shown to lyse recombinant vaccinia virus-infected cells that synthesize the HIV-1 envelope glycoprotein gp160. The processing of endogenously synthesized gp160 for recognition by CD4+ T cells required that the protein, after synthesis on the rough endoplasmic reticulum and during subsequent cellular transport, remain attached to the luminal/extracellular membrane face by a hydrophobic anchor sequence.