[High-sensitivity C-reactive protein: a new risk factor of coronary disease]. / La protéine C-réactive hypersensible (CRPhs): un nouveau facteur de risque de maladie coronarienne?

CRP is an acute-phase protein released after an infection or an inflammation. Atherosclerosis is actually believed to result from the combination of lipid deposits in the arterial wall together with inflammatory cells. Numerous prospective studies have shown that the serum level of CRPhs is a strong predictor of future coronary events. The risk of such events is twice as high in patients with mean CRPhs values of 2.4 mg/l than in patients with values of 1 mg/l. Serum levels of CRPhs have been measured in 265 of our patients with normal sedimentation rate. Mean levels were 1.5 + 1.5 mg/l in men and 1.64 + 1.5 mg/l in women. Levels were higher in obese and diabetic patients. CRP levels can be slightly increased in arthritis. Serum levels double in women treated by oral estrogens after menopause. CRP should be measured at least 4 weeks after an infection such as a viral rhinitis. CRP levels decrease by 15 to 30% after treatment with glitazone (rosiglitazone) and with statins. The effect of aspirin is controversial. The magnitude of the preventive effect of aspirin and of statins on coronary risks could depend on the basal level of CRPhs. If these data are confirmed, it would be easier to select those patients who would be the most likely to benefit from the antiinflammatory treatments.

Transmembrane signaling changes with aging.

Altered immune response and transmembrane signaling with aging has previously been demonstrated. The aim of the present study was to characterize PMNLs and lymphocyte G proteins and to determine whether their relative amounts are altered with aging. First we studied the effects of FMLP on PMNLs IP3 formation. It was found that in any group of elderly the PMNLs IP3 formation was significantly decreased compared to that of young subjects. In FMLP receptor binding affinity no measurable difference exists in either low- or high-affinity FMLP receptors. The autoradiogram of 32P-ADP-ribosylated proteins by CT in lymphocytes of young individuals showed a major polypeptide of 40 kDa, and two much less prevalent components of 52 and 45 kDa. In contrast, in lymphocytes of elderly subjects the major polypeptide was 45 kDa, and the two others were very weakly labeled. In PMNLs, CT labeled the 45-kDa band quite strongly, mainly in the elderly, and the 52- and 40-kDa bands were very weakly labeled, mainly in young subjects. When PT was used, no age-related pattern changes could be demonstrated, while differences could be observed between the two types of cells.

Altered functions of peripheral blood monocytes in homosexual males and intravenous drug users with persistent generalized lymphadenopathy.

Persistent generalized lymphadenopathy (PGL) is observed predominantly in subjects at risk of developing AIDS. Twenty-seven individuals belonging to such groups: twelve homosexual males and fifteen intravenous drug users, were investigated for immunological abnormalities with particular attention to monocyte functions. They were compared with five AIDS patients. Twenty out of twenty-two individuals had anti-LAV/HTLV-III antibodies and most had abnormalities characteristic of AIDS: polyclonal hypergammaglobulinemia, decreased cell-mediated immunity, inverted T-cell helper/suppressor ratio and histological alterations of lymph nodes. As for peripheral blood monocyte functions, phagocytic capacity and production of O2- were normal and bactericidal capacity was decreased. Monocytes cultured in the presence of concanavalin A produced less PGE2 and more IL-1/MCF than normal monocytes. Similar abnormalities were found using monocytes from AIDS patients. These data suggest that monocytes from patients with PGL have functional alterations that may be either intrinsic or secondary to lymphocyte dysfunction(s); these alterations do not account for the decreased capacity of lymphocytes to respond to mitogens but may explain the uncontrolled activation of B cells.

[Persistent generalized lymphadenopathies in homosexuals and drug addicts: changes in humoral and cellular immunity]. / Lymphadénopathies persistantes généralisées chez les homosexuels et les toxicomanes: altérations de l'immunité humorale et cellulaire.

In two groups of subjects at risk for acquired immune deficiency syndrome (AIDS), homosexual males and intravenous drug users with persistent generalized lymphadenopathy, humoral and cell-mediated immunity were compared. A small group of patients with definite AIDS were also studied. It was found that levels of immunoglobulins, serological markers for virus and other infections, cell-mediated immunity and histology of lymph nodes were similar in homosexuals and drug users, whereas the lymphocyte sub-populations differed completely. The number of T4+ lymphocytes was markedly decreased in homosexuals but normal in drug users; the number of T8+ lymphocytes was much higher in drug users than in homosexuals. This discrepancy may explain the extremely low prevalence of AIDS cases observed among Swiss drug users as compared with the high frequency noted among homosexuals.

Macro-creatine kinase type 1. Immunological studies in 14 patients with comments on clinical significance.

Circulating autoantibodies directed at creatine kinase (CK) BB isozyme are detected in plasma in the form of an immune complex (immunoglobulin CK BB) termed macro-CK type 1. Fourteen patients presented a falsely elevated CK MB isozyme fraction as measured by the immunoinhibition method; they were found to have IgG-CK BB complexes, which was considered to be indirect evidence of circulating anti-CK BB autoantibodies. No evident clinical association between the detection of this autoantibody in complexed form and autoimmune disease could be established, there was no significantly increased incidence of other autoantibodies, and there was no specific alteration in immunoglobulin and complement levels; however, the HLA haplotype A1,B8,DR3, which is known to be associated with autoimmunity, was present in five patients.

Low levels of functional of alpha 1-proteinase inhibitor in the promotion of C3-cleavage by granulocyte-neutral proteases in pleural empyema.

It has been suggested that C3 breakdown by granulocyte-neutral proteases in pleural empyemas may be related to a decreased inhibitor potential for these enzymes. In the present study it was shown that in 17 infected pleural effusions, high proteolytic activity on 125I-labeled C3 (16.3% +/- 4.4%) correlated with low functional levels of alpha 1-proteinase inhibitor (alpha 1-PI), as determined by trypsin-inhibitory capacity (56.2 +/- 20.1 IU/ml; rs = -0.97, P less than .001), whereas in 18 sterile pleural effusions there was no such correlation (125I-labeled C3 cleavage, 2.2% +/- .2%; trypsin-inhibitory capacity, 192.6 +/- 26.7 IU/ml). However, alpha 1-PI and alpha 2-macroglobulin protein concentrations in infected and sterile effusions (as measured by immunodiffusion) were similar. Fifteen strains of three bacterial species--Streptococcus pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis--isolated from patients with pneumonia or empyema inactivated the elastase-inhibitory capacity of alpha 1-PI in vitro. These results show that in empyemas functional levels of alpha 1-PI were too low to inactivate granulocyte elastase and that some bacterial species may contribute to the low inhibitor potential of infected pleural fluid by direct alpha 1-PI inactivation.

Phagocytosis, bactericidal capacity, and PGE2 production of monocytes in systemic lupus erythematosus and rheumatoid arthritis.

Peripheral blood monocytes from 10 systemic lupus erythematosus (SLE) and 10 rheumatoid arthritis (RA) patients as well as from 24 controls were studied for such functions as phagocytosis, bactericidal capacity, iodination, and PGE2 production. Phagocytosis of opsonized erythrocytes, exploring only the Fc receptor, was increased in SLE and RA. Killing of Staphylococcus aureus was decreased in both SLE and RA in the presence of AB serum, but not in the presence of autologous serum. Iodination was, on the average, normal in SLE and elevated in RA. Prostaglandin E2 production was decreased in SLE (except with the highest concentration of Con A) and increased in RA. In SLE, functional alterations were more pronounced in clinically active than in inactive disease. These results show that in SLE and RA peripheral blood monocytes have alterations of their functions that are independent of serum factors. It is suggested that these abnormalities may be relevant to the pathogenetic mechanisms and evolution of these diseases.

Functional and biochemical characteristics of human "null" lymphoid cells.

Human peripheral null cells (non-T and non-B lymphocytes) were isolated by removing B lymphocytes and monocytes on nylon-wool columns and by E rosette-forming cells depletion. The null cell population contained less than 1% of SIg-bearing cells, cells with complement receptors (EAC+), and E mouse rosette-forming cells, but was contaminated by about 5% of T lymphocytes and 10% of monocytes. High affinity Fc receptors were present on 12% of the null cells. No intracytoplasmic immunoglobulins (CIgs) were detected by immunofluorescence. Culture of these null cells for 2 to 6 days did not modify their surface receptors. Null cells were not stimulated to undergo blastogenesis by the following mitogenic agents: concanavalin A (Con A), phytohemagglutinin-L (PHA-L), lentil lectin, wheat germ agglutinin, pokeweed mitogen (PWM), peanut agglutinin, and neuraminidase-galactose oxidase. PWM did not induce the transformation of null cells into B lymphocytes and no SIg, CIg, and production of Ig were detected by immunofluorescence and by measuring the incorporation of 3H-leucine. However the antibody-dependent cellular cytotoxicity of these null cells was very active compared to unpurified lymphocytes. Analysis of the lectin-binding surface glycoproteins, after labeling of the cells, by polyacrylamide gel electrophoresis (PAGE), showed that the 27,000- to 33,000-dalton component (Ia-like antigen) present in large amounts on B lymphocytes and monocytes was absent in null cells. These results are in agreement with the hypothesis that null cells consist of one or several populations different from the other lymphocytes and that they are not direct precursors or immature T and B lymphocytes.

Demonstration of a local exhaustion of complement components and of an enzymatic degradation of immunoglobulins in pleural empyema: a possible factor favouring the persistence of local bacterial infections.

Local bacterial infections such as abscesses or purulent exudates most often contain numerous, easily culturable bacteria despite an intense inflammatory reaction characterized by the ingress of polymorphonuclear leucocytes. In order to understand the mechanisms leading to such a persistent infection, we used pleural empyema as a model and measured the levels and catabolism of complement as well as of immunoglobulins in 28 infectious pleural effusions associated with either a positive or with a negative bacterial culture. Classic and alternative pathway haemolytic activities, factor B and C4 haemolytic activities as well as native C3 were markedly decreased or undetectable in most culture-positive effusions when compared to culture-negative effusions (P less than 0.005); breakdown products of factor B and C3 were markedly increased in culture-positive fluids. Eleven out of 14 culture-positive fluids exhibited IgG breakdown as opposed to none of the culture-negative fluids. In seven out of 14 culture-positive fluids, incubation with 125I-IgG led to their in vitro breakdown. This proteolytic activity could be abolished by preincubation of the culture-positive fluids with normal sera. Thus, increased catabolism of complement and breakdown of immunoglobulins, both leading to local consumption of immune reactants, could be one of the causes for bacterial persistence in pleural empyema.

Comparison between surface components from human B and chronic lymphatic leukaemia lymphocytes isolated by lentil lectin.

Peripheral blood lymphocytes from patients with chronic lymphatic leukaemia (CLL) were compared to normal purified B lymphocytes. Lymphocytes were cultured in the presence of 3H-fucose, and glycoproteins isolated by lentil lectin, were analysed by sodium dodecyl sulphate polyacrylamide gel electrophoresis. Most of the major components detected in normal B lymphocytes were also present in CLL lymphocytes. Although B and CLL lymphocytes shared several components of similar molecular size, the latter appeared to be a heterogeneous cell population. The most important finding was the presence of a prominent component of approximately component of approximately 35,000 daltons in normal B and in 7 out of 8 cases of CLL. This component was not related to surface immunoglobulins but appeared to have a molecular weight very similar to the human Ia-like antigen. A labelled component of approximately 140,000 daltons was also present in large amounts in B lymphocytes and in 5 cases of CLL. Receptors specific for CLL lymphocytes were not found.

Surface glycoproteins from human T, B and chronic lymphatic leukemia lymphocytes isolated by 3 different lectins.

Glycoproteins from the surface of human T. B and leukemic lymphocytes were isolated and partially characterized by using three different lectins, Lens culinaris lectin (Lc), wheat germ agglutinin (WGA) and phytohemagglutinin from Phaseolus vulgaris (PHA). Cells were labelled either with I125 or 3H-fucose and lysed with detergent. Labelled components were isolated by incubation with lectins and anti-lectin antisera and immune precipitates were analysed by SDS-polyacrylamide gel electrophoresis. The results obtained show: 1) components with a molecular weight of 35,000-27,000 daltons were detected by the three lectins in both B and CLL lymphocytes but not in T lymphocytes; these components have a molecular weight similar to the Ia like antigen; 2) B and CLL lymphocytes were found to share several components of similar molecular size and specially the 35,000-27,000 daltons receptors; 3) in T lymphocytes, the 35,000-27,000 daltons components were absent, but components of low molecular weight, about 23,000, were easily detected. These data indicate that lectins bind to several identical receptors on the surface of different lymphocytes populations but also to some specific components.