Ahmed A. Wadee

ACUTE PHASE PROTEINS IN MAJOR DEPRESSION

Extensive evidence exists associating depression with changes in the immune system. The present study evaluates the levels of complement components C3 and C4, C-reactive proteins, and IL-6 in patients who met DSM-III-R diagnostic criteria for major depressive disorder, as well as controls. Whereas no significant differences between the mean levels of C3 could be detected between depressed patients and controls, the levels of C4, IL-6 (where detected), and C-reactive protein were significantly raised in the group with a depressive disorder. Our study suggests an interaction between psychological state and immune systems operative in host defenses.

Defective monocyte function in patients with systemic lupus erythematosus

Peripheral blood adherent cells from patients with systemic lupus erythematosus (SLE) were shown to have markedly reduced phagocytic activity as compared to normal adherent cells or those from non-SLE patients receiving corticosteroid therapy. Both resting and phagocytosing monocytes showed decreased hexose monophosphate shunt and glycolytic activity. Mononuclear cells from SLE patients showed grossly impaired proliferative activity after NaIO4 activation. Furthermore, addition of SLE adherent cells to normal adherent cell-depleted lymphocytes decreased [3H]thymidine incorporation of the latter cells following NaIO4 treatment. Addition of normal adherent cells to SLE lymphocytes corrected the previous defect, indicating that an adherent abnormality is responsible for the defect in SLE mononuclear cell proliferation to NaIO4 activation.

Influence of ultra-endurance exercise on immunoglobulin isotypes and subclasses.

Background: Strenuous exercise is associated with tissue damage. This activates the innate immune system and local inflammation. Interaction between innate and adaptive immunity is essential for maintaining health, suggesting that the adaptive immune system may also be altered by exercise. Objectives: To determine exercise induced changes in the adaptive immune system by measuring the immunoglobulin isotype and subclass response to an ultra-marathon. Methods: Venepuncture was performed on 11 experienced volunteers (six men, five women; mean (SD) age 43 (9.8) years) 24 hours before the projected finishing time and immediately after and 3, 24, and 72 hours after an ultra-marathon (90 km). Serum was stored at −80°C. IgM, IgD, IgA, IgG, IgG1, 2, 3, and 4, and total IgE were measured. Results: The following immunoglobulins were significantly (p⩽0.05) altered after the race: IgD, immediately (−51%) and 24 hours (−41%) after; IgM 24 hours after (−23%); total IgG immediately after (+12%). There were no reports of symptoms of upper respiratory tract infections after the ultra-marathon. Conclusions: In experienced ultra-endurance runners, alterations in immunoglobulin concentrations after a race suggest an enhanced immune response, including isotype switching, interactions with the innate immune system, and a secondary antibody response. These alterations may have a role in the maintenance of subject health after an ultra-marathon.

Fruit allergy: Demonstration of IgE antibodies to a 30 kd protein present in several fruits

A patient who had experienced allergic responses to various fruits developed an acute anaphylactic reaction after the ingestion of a local strain of cling peaches. The patients serum, but not control sera, contained IgE antibodies reactive to extracts from peaches, guavas, bananas, mandarins, and strawberries in an ELISA. The patients serum, however, did not demonstrate elevated levels of IgE antibodies to extracts from apples, pears, and nectarines. Adsorption of the patients serum with extracts from peaches, strawberries, and mandarins resulted in a decline of detectable IgE antibodies to these fruits. Adsorption with extracts from apples and pears had no such effect. These results demonstrate the specificity of the patients IgE antibodies to selected fruits only. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by Western blotting revealed a 30 kda of protein that was recognized by the IgE antibodies in the patients serum. This protein was not present in extracts from pears or apples. Our results highlight the importance of specific allergens in considering acute allergic reactions to individuals exhibiting sensitivity to various foods or fruits.

Circulating Cytokine Profiles and Their Relationships with Autoantibodies, Acute Phase Reactants, and Disease Activity in Patients with Rheumatoid Arthritis

Our objective was to analyse the relationship between circulating cytokines, autoantibodies, acute phase reactants, and disease activity in DMARDs-naïve rheumatoid arthritis (RA) patients (n = 140). All cytokines were significantly higher in the RA cohort than in healthy controls. Moderate-to-strong positive intercorrelations were observed between Th1/Th2/macrophage/fibroblast-derived cytokines. RF correlated significantly with IL-1β, IL-2, IL-4, IL-10, IL-12, G-CSF, GM-CSF, IFN-γ, and TNF (P < .0001), and aCCP and aMCV with IL-1β, IL-2, IL-4, and IL-10 (P < .0002), while IL-6 correlated best with the acute phase reactants, CRP, and SAA (P < .0001). In patients with a DAS28 score of ≥5.1, IFN-γ, IL-1β, IL-1Ra, TNF, GM-CSF, and VEGF were significantly correlated (P < .04–.001) with high disease activity (HDA). Circulating cytokines in RA reflect a multifaceted increase in immune reactivity encompassing Th1 and Th2 cells, monocytes/macrophages, and synovial fibroblasts, underscored by strong correlations between these cytokines, as well as their relationships with RF, aCCP, and aMCV, with some cytokines showing promise as biomarkers of HDA.

The inhibitory effects of Mycobacterium tuberculosis on MHC class II expression by monocytes activated with riminophenazines and phagocyte stimulants

The expression of MHC class II antigens by peripheral blood monocytes from normal individuals was investigated. Class II expression as determined by a cell HLISA was effectively induced by various phagocyte stimulants. A further aspect of our study investigated the effects of clofazimine, a riminophenazine antimicrobial agent and its analogue, B669, on class II expression. Both agents at concentrations attainable in vivo increased the expression of MHC class II antigens. A 25‐kD glycolipoprotein derived from Mycobacterium tuberculosis that inhibits phagocyte functions has previously been described. This component significantly reduced the expression of MHC class II antigens induced by the riminophenazines, clofazimine and B669, interferon‐gamma (IFN‐γ) or opsonised yeast when added at the initiation of experiments. The riminophenazines could not restore the decrease in class II antigen expression previously inhibited by the 25‐kD mycobacterial fraction. However, cultures prestimulated with the riminophenazines or phagocyte stimulants were unaffected by the 25‐kD mycobacterial fraction. The results suggest the potential use of these agents as modulators of phagocyte function.

Common HLA alleles associated with health, but not with facial attractiveness

Three adaptive hypotheses have been proposed to explain the link between the human leucocyte antigen (HLA) genes, health measures and facial attractiveness: inbreeding avoidance, heterozygote advantage and frequency-dependent selection. This paper reports findings that support a new hypothesis relating HLA to health. We suggest a new method to quantify the level of heterozygosity. HLA heterozygosity did not significantly predict health measures in women, but allele frequency did. Women with more common HLA alleles reported fewer cold and flu bouts per year, fewer illnesses in the previous year and rated themselves healthier than women with rare alleles. To our knowledge, this is the first study to show a positive correlation between HLA allele frequency and general health measures. We propose that certain common HLA alleles confer resistance to prevalent pathogens. Nevertheless, neither HLA heterozygosity nor allele frequency significantly predicted how healthy or attractive men rated the female volunteers. Three non-mutually exclusive explanations are put forward to explain this finding.

In vitro Effects of Histamine on Eosinophil Migration

Histamine at concentrations of 5 X 10(-6) to 5 X 10(-5) M increased eosinophil movement to endotoxin-activated serum (EAS). This effect was due entirely to stimulation of random migration (chemokinesis). Directional motility (true chemotaxis) was inhibited by these concentrations. Regulation of chemotaxis was apparently mediated via an H2 receptor as metiamide, an H2 receptor antagonist, but not diphenylhydramine hydrochloride, an H1 receptor antagonist, blocked the histamine-induced inhibition of chemotaxis. Both histamine and metiamide when used alone had no effect on eosinophil motility. The histamine effects on motility were associated with increased levels of intracellular cAMP, whereas cGMP levels were not affected.

Clinical and serological correlates of antinucleosome antibodies in South Africans with systemic lupus erythematosus

Antinucleosome antibodies (AnuA) are increasingly recognized as an important biomarker in the diagnosis and subset stratification of patients with systemic lupus erythematosus (SLE). The aim of the study was to determine the sensitivity, specificity, and clinico-serological correlates of AnuA in black South Africans with SLE. We performed a cross-sectional study of 86 SLE patients attending a tertiary center and 87 control subjects. AnuA were tested using a second-generation enzyme-linked immunosorbent assay (ELISA). The sensitivity, specificity, positive predictive value, and negative predictive value of AnuA were 45.3, 94.3, 88.6, and 63.6%, respectively. The presence of AnuA were strongly associated with the co-presence of anti-dsDNA antibodies (OR = 3.4, p < 0.0005) and antihistone antibodies (OR = 15.7, p < 0.00001). Patients who were seropositive for AnuA were more likely to have skin involvement (discoid lupus and/or malar rash) and had higher SLE disease activity index (SLEDAI) scores and Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) damage scores (p < 0.05). IgG anticardiolipin antibody (aCL) levels showed a significant correlation with AnuA ratios (p < 0.01). Our findings provide further evidence that AnuA are a sensitive and specific diagnostic biomarker in SLE. Moreover, our finding that the presence of AnuA, but not anti-dsDNA antibodies, are associated with worse SLICC/ACR damage scores suggest that AnuA may have a role in predicting disease outcome. The correlation between IgG aCL and AnuA is a novel finding that merits further studies to determine possible common peptide specificities of the antibodies.

Serum concentrations of C reactive protein, α1 antitrypsin, and complement (C3, C4, C1 esterase inhibitor) before and during the Vuelta a Espańa

Objectives: To determine serum concentrations of proinflammatory (C reactive protein, complement C3 and C4) and anti-inflammatory (α1 antitrypsin, C1 esterase inhibitor (C1-INH)) acute phase proteins in elite cyclists before and during a three week cycle tour. Methods: Seventeen professional cyclists participating in the Vuelta a Espańa volunteered for the study. Their mean (SD) physical characteristics were: age 28 (1) years; height 1.7 (0.06) m; weight 65 (7) kg; body fat 7.6 (0.8)%; Vo2max 75.3 (2.3) ml/kg/min. Venepuncture was performed on each subject 24 hours before the tour began (T0), on day 11 (the first rest day; T1) and day 21 (the second to last stage of the tour; T2). Samples at T1 and T2 were taken about 17 hours after the previous stage. Analysis of variance was used to determine changes over time. Where significance was found, a Tukey post hoc test was performed. Results: C reactive protein concentrations were consistently within the normal range, although there was a 228%, non-significant increase at T1. C3 concentrations fell within the normal range at all times assessed. C4 concentrations before the race were within the normal range and were significantly increased 10 days (T1) into the race. C1-INH concentrations did not change significantly throughout the race. α1 Antitrypsin concentration before the race was at the lower end of the normal range and was only significantly raised at T2. Conclusions: Although not as pronounced as those reported in marathon/ultramarathon runners, elite cyclists participating in a three week cycle tour experienced increases in selected proinflammatory and anti-inflammatory acute phase proteins, indicating an acute phase/inflammatory response. It is tenable that the increase in α1 antitrypsin and C1-INH (anti-inflammatory mediators) at T2 served to attenuate the acute phase/inflammatory response. The lower than normal resting concentrations of the acute phase proteins supports the notion that chronic aerobic exercise induces an anti-inflammatory state.