James D. Folds

Progression to AIDS: the effects of stress, depressive symptoms, and social support.

OBJECTIVE We examined the effects of stress, depressive symptoms, and social support on the progression of HIV infection. METHODS Eighty-two HIV-infected gay men without symptoms or AIDS at baseline were followed up every 6 months for up to 5.5 years. Men were recruited from rural and urban areas in North Carolina as part of the Coping in Health and Illness Project. Disease progression was defined using criteria for AIDS (CD4+ lymphocyte count of <200/microl and/or an AIDS-indicator condition). RESULTS We used Cox regression models with time-dependent covariates, adjusting for age, education, race, baseline CD4+ count, tobacco use, and number of antiretroviral medications. Faster progression to AIDS was associated with more cumulative stressful life events (p = .002), more cumulative depressive symptoms (p = .008), and less cumulative social support (p = .0002). When all three variables were analyzed together, stress and social support remained significant in the model. At 5.5 years, the probability of getting AIDS was about two to three times as high among those above the median on stress or below the median on social support compared with those below the median on stress or above the median on support, respectively. CONCLUSIONS These data are among the first to demonstrate that more stress and less social support may accelerate the course of HIV disease progression. Additional study will be necessary to elucidate the mechanisms that underlie these relationships and to determine whether interventions that address stress and social support can alter the course of HIV infection.

Comparison of Granulocyte Colony-Stimulating Factor (G-CSF)-Mobilized Peripheral Blood Progenitor Cells and G-CSF-Stimulated Bone Marrow as a Source of Stem Cells in HLA-Matched Sibling Transplantation

HLA-identical bone marrow or stem cell transplantation from a sibling is the preferred treatment for patients with chronic myelogenous leukemia, bone marrow failure syndromes, relapsed acute leukemia, and specific inborn errors of metabolism. Several groups have shown that granulocyte colony-stimulating factor (G-CSF)--mobilized peripheral blood progenitor cells (PBPCs) obtained from HLA-matched siblings are effective in reconstitution of marrow function after marrow ablative conditioning therapy. To evaluate whether G-CSF treatment before bone marrow harvest leads to enhanced recovery of PBPC counts and recovery from limited graft-versus-host disease (GVHD), we assessed the outcome of a sequential cohort of patients treated identically and then given either G-CSF--mobilized PBPCs or G-CSF--stimulated bone marrow from HLA-identical siblings. We show that the time to neutrophil engraftment is identical in the 2 cohorts, whereas platelet engraftment is earlier with the use of PBPCs. The incidence of acute GVHD was decreased, and that of chronic GVHD significantly decreased, in the group receiving bone marrow. Overall survival was not different between the 2 groups. Thus, G-CSF--stimulated bone marrow offers a source of stem cells that allows for early neutrophil engraftment with a decreased risk of GVHD.

Major depression and immunity: Preliminary evidence of decreased natural killer cell populations

1. Alterations in cellular immunity have been suggested to occur in major depressed patients. 2. To investigate the populations of B-cells, T-cells and T-cell subsets in major depression, the authors utilized monoclonal antibody techniques to enumerate the number of total lymphocytes, B-cells and T-cell subpopulations in recently admitted patients with major depression or non-affective disorders. 3. The authors also studied the relationship between the immune state and hypercortisolism as measured by post-dexamethasone serum cortisol. 4. The preliminary findings from this pilot study suggest that major depressed patients may have altered cellular immunity as demonstrated by lower numbers of natural killer cells. 5. Further study will be necessary to confirm the trend for lower numbers of T-cell lymphocytes and T-cell subpopulations including helper cells, suppressor cells and natural killer cells in patients with non-suppression of serum cortisol following dexamethasone.

Immediate effects of intravenous IgG administration on peripheral blood B and T cells and polymorphonuclear cells in patients with myasthenia gravis

Five patients with myasthenia gravis, who received treatment with intravenous 7S γ-globulin were monitored for changes in immunological status. Serum immunoglobulin G increased from an average of 1.4 to 4.7 g/dl during the 5-day course of therapy. Specific antibody to the acetylcholine receptor present in three of five patients did not change. A transient decrease in total peripheral blood leukocytes was observed in five patients due to decreases in the absolute number of polymorphonuclear cells and lymphocytes in the circulation. Lymphocyte surface marker studies revealed that the percentage of surface immunoglobulin positive cells increased in all patients from an average of 13 to 26% by day 5 of therapy; however, the percentage of HLA-Dr- and Leu 12 (CD19)-positive B cells did not change. Lymphoid cells positive for the Leu 11 (CD16) marker doubled from an average of 11 to 24% during the 5-day course of therapy. Surface Ig-positive cells and Leu 11 (CD16)-positive cells returned to pretreatment values by 7 days posttherapy. Helper/suppressor cell ratios slowly decreased in all patients from an average of 2.9 to 2.2 by 1 week posttherapy and remained low for several weeks.

Cell-mediated immunity during syphilis. A review

Evidence is presented which reinforces the complexity of the host-parasite interaction during the course of syphilis. Infection with Treponema pallidum evokes a complicated antibody response and an assortment of cell-mediated immune reactions in the host. It appears that humoral immunity plays a minor role towards the complete elimination of syphilitic infection while the cellular limb of the immune response may be an important host defence mechanism. Information now available indicates that a state of anergy, or immunosuppression, exists in the early stages of human and experimental rabbit syphilis based upon negative skin reactions to T. pallidum antigen(s), the abnormal histological appearance of lymphoid organs, and impaired in vitro lymphocyte reactivity. It is also evident that in the later stages of the disease cellular immunity becomes activated as delayed type skin reactions can normally be elicited in tertiary syphilitics and lymphocyte behaviour in cell culture appears normal. Several mechanisms have been invoked to explain the delay in an effective immune response against syphilitic infection and the duration of the disease: (1) a capsule-like substance on the outer surface of virulant T. pallidum may act as a barrier against treponemicidal antibody; (2) this material and other biological properties of virulent treponemes could enable spirochaetes to escape being engulfed by macrophages and other phagocytic cells; (3) antigenic competition among different treponemal antigens causing partial tolerance; (4) T. pallidum infection may bring about the elaboration of immunosuppressive substances of host or treponemal origin which inhibit the proper function of lymphocytes, macrophages, and other cell types.

Practical Evaluation of Methods for Detection and Specificity of Autoantibodies to Extractable Nuclear Antigens

ABSTRACT Detection and specificity of autoantibodies against extractable nuclear antigens (ENA) play a critical role in the diagnosis and management of autoimmune disease. Historically, the detection of these antibodies has employed double immunodiffusion (DID). Autoantibody specificity was correlated with diagnoses by this technique. Enzyme immunoassays have been developed by multiple manufacturers to detect and identify the specificity ENA autoantibodies. To address the relationship of ENA detection by DID and enzyme immunoassay, the performances of five immunoassays were compared. These included two DID and three enzyme-linked immunoassays (ELISA) (both screening and individual antigen profile kits). The sample set included 83 ENA-positive, antinuclear-antibody (ANA)-positive specimens, 77 ENA-negative, ANA-positive specimens, and 20 ENA- and ANA-negative specimens. Sensitivity and specificity were calculated by two methods: first, by using the in-house DID result as the reference standard, and second, by using latent class analysis, which evaluates each kit result independently. Overall, the results showed that the ELISA methods were more sensitive for detection of ENA autoantibodies than DID techniques, but presence and/or specific type of ENA autoantibody did not always correlate with the patients clinical presentation. Regardless of the testing strategy an individual laboratory uses, clear communication with the clinical staff regarding the significance of a positive result is imperative. The laboratory and the clinician must both be aware of the sensitivity and specificity of each testing method in use in the clinical laboratory.

Neutral proteases confined to one class of lysosomes of human polymorphonuclear leukocytes.

Summary We find that protease and esterase activity of human PMN exist in a latent form in a class of membrane-bound particles which sediment at a distinctive density. Readily separated from these granules by sucrose density gradient centrifugation is a separate class of particles, which is associated with an aminopeptidase not previously described in human PMN lysosomal granules. Protease, esterase, and aminopeptidase act optimally at or near pH 7.2.

High Versus Low Basal Cortisol Secretion in Asymptomatic, Medication-free HIV-infected Men: Differential Effects of Severe Life Stress on Parameters of Immune Status

Abstract The authors hypothesized that HIV-infected men with high basal cortisol secretion would exhibit greater stress-related reductions in the ratio of Th1 /Th2 cell-derived cytokines and numbers ofCD8+ T and NK lymphocytes than low basal cortisol secretors. A semistructured interview was used to assess life stress during the preceding 6 months of 94 HIV-infected men classfied as high and low cortisol secretors (n = 47/group). Increased levels of severe life stress were highly correlated with lower numbers of CD8+ T cells, CD16+ and CD56+ NK cells, CD57+ cells, and higher DHEA-S concentrations in the high cortisol group. Conversely, no significant correlations were found in the low cortisol group. No correlations were found between stress and CD4+ T helper/ inducer cell counts, cytokine production, or testosterone levels in either participating group. These data suggest that severe stress in combination with high glucocorticoid activity may modify select parameters of immune status in HIV-infected men.

Comparison of a lysed whole blood method to purified cell preparations for lymphocyte immunophenotyping: differences between healthy controls and HIV-positive specimens

Although the majority of clinical laboratories now use a lysed whole blood (LWB) method for routine immunophenotyping, researchers wishing to perform other types of studies with lymphocytes from HIV+ patients may still need to use purified cell preparations, such as peripheral blood mononuclear cells (PBMC). A comparison study of the two methods was performed, using peripheral blood specimens from normal donors and from patients infected with the human immunodeficiency virus (HIV+). Reproducibility studies and several types of holding studies (both before and after specimen processing) were also performed. The results suggest that the two different methods of sample preparation have different effects upon abnormal patient specimens than those observed in healthy controls. Immunophenotyping results derived from the two different methods cannot be considered equivalent for the purposes of quantitating the presence of a particular type of cell.

Interaction of human polymorphonuclear leukocyte elastase with human IgM. In vitro production of an Fabμ-like fragment

Human granulocyte elatase has ample opportunity to interact with immunoglobulins at both the intracellular and extracellular level. Thus, the susceptibility of human IgM to proteolysis by this enzyme was investigated. Treatment of monoclonal IgM with elastase in the presence of 2 mM cysteine for 18 hr at 37°C resulted in the formation of a major fragment (Frag. A) and small peptides. Fragment A had an approximate mol. wt of 50,000 as determined by gel filtration. Reduction and subsequent sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of Frag. A revealed 2 bands having mol. wt of 23,000 and 30,000, respectively. Ouchterlony analysis showed Frag. A to contain light (K) chain and a portion of the heavy (μ) chain. Fragment A appeared to be antigenically identical with Fab produced by trypsin or papain digestion of IgM but completely different from Fc5μ produced by trypsin digestion of IgM. Fc5μ was digested to small peptides by the enzyme. These findings show that human PMN elastase can specifically degrade IgM in vitro, producing an Fab-like fragment and small peptides.