Evaluation of chemiluminescence, procoagulant activity and antigen presentation by monocytes from lepromatous leprosy patients with or without reactional episodes.

In this study, we evaluated the activity of peripheral blood mononuclear cells (PBMC), isolated from treated and untreated lepromatous leprosy patients, from lepromatous leprosy patients during and after reactional episodes (erythema nodosum leprosum (ENL) and reversal reaction (RR)), and from normal healthy individuals. We determined reactive oxygen intermediate (ROI) production, procoagulant activity (PCA) and HLA-DR antigen expression of monocytes, besides lymphoproliferation, both in the presence and absence of various stimulatory agents. Phorbol myristate acetate (PMA) stimulated ROI production by monocytes from all the groups studied, with patients during reactional episodes (ENL and RR) showing a significantly higher response (p < 0.009 and p < 0.00001). Irradiated Mycobacterium leprae, although having little effect when added alone, strongly suppressed PMA-stimulated ROI production. Muramyl dipeptide (MDP) had no influence on either basal or on PMA-induced ROI production. Basal monocyte PCA, as well as M. leprae or concanavalin A (ConA)-induced monocyte PCA was comparable in monocytes from all the groups studied. ConA was able to induce mitogenic activity in mononuclear cells isolated from all the groups studied. M. leprae, although stimulatory for normal individuals, did not induce lymphoproliferation in lepromatous leprosy patients, except for cells from patients during RR, which responded equally to M. leprae and to ConA. The absence of M. leprae-induced lymphoproliferation in lepromatous leprosy patients is not caused by the lack of basal HLA-DR expression, as PBMC from all individuals studied showed the same level of this antigen. Our results suggest an increase of spontaneous or PMA-induced monocyte activity, as detected by ROI production, during the reactional episode; addition of M. leprae suppressed this response. The increase in monocyte activity could be correlated with the increase of lymphoproliferation response to M. leprae during RR, but not during ENL. The importance of a possible immune suppressive action of M. leprae is discussed.

An unusual case of Hansen's disease (lepromatous leprosy) with circulating anticoagulant and macroglobulinemia.

A 42-year-old Mexican migrant laborer with a previous history of neurofibromatosis presented with a stuffy nose and chronic ulceration of his soft palate. Multiple subcutaneous nodules were found on his skin, and laboratory investigation revealed an elevated activated partial thromboplastin time (APTT). Further laboratory evaluation showed a lupus-like circulating anticoagulant deemed IgM by quantitative immunoglobulin studies. Although coagulation defects in lepromatous leprosy are rare, the preoperative preparation of a patient with leprosy may require a screening prothrombin time (PT), APTT and platelet count. Abnormalities in these values may indicate the need for specific factor assays and a search for circulating anticoagulant.

Anticardiolipin antibodies in patients with infectious diseases.

IgG or IgM anticardiolipin antibodies were present in the sera of 67% of 33 patients with Hansen's disease, in 53% of 30 patients with tuberculosis and in 50% of 16 patients with endocarditis. Despite the high frequency of these antibodies, no patient had a history of thrombosis or abortion. Anti-denatured DNA antibodies were tested in patients with tuberculosis and patients with Hansen's disease. Only in the latter group did we observe a statistically significant association between anticardiolipin and anti-denatured DNA antibodies. Anticardiolipin binding activity, however, could not be inhibited by preincubation of sera with a variable concentration of denatured DNA. These data suggest that: a) Anticardiolipin antibodies in infectious diseases do not necessarily participate in the pathogenesis of thrombotic or obstetric complications; b) Anti-denatured DNA and anticardiolipin antibodies in the population studied do not have a cross-reaction.

[Immunologic factors and platelet vessel wall interactions (author's transl)]. / Facteurs immunologiques et interactions entre plaquettes et paroi vasculaire.

Platelet subendothelium interaction is an essential step in thrombosis and hemostasis which can be modulated by immunoglobulins, immune complexes, complement, and leukocytes. Antiplatelet antibodies can induce thrombocytopenia which is accompanied by a reduced vascular wall thickness and an increased fenestration. Antigen-antibody complexes can activate platelets inducing platelet release and aggregation. This reaction is amplified by the first component of complement C1q. Cytotoxic antibodies directed against endothelial cells have been observed in transplantation. These antibodies can be directed against HL-A antigens or specific endothelial antigens. Anticollagen antibodies have been detected in patients with leprosy. The C1q component can inhibit adhesion of platelets to collagen and platelet aggregation induced by collagen. The association of acquired or congenital C1q deficiency and vasculitis has been reported. C3a is taken up by endothelial cells and metabolized. C3a and C5a can modify vessel wall permeability and activate granulocytes which can become toxic for endothelial cells. Leukocyte cationic protein can reduce platelet aggregation. An anti-von Willebrand antibody could be the origin of hemostatic abnormalities and endothelial lesions. The involvement of immunologic factors in platelet vessel wall interactions is complex. Immune complexes and some antibodies seem capable of promoting thrombosis, while a component of complement (C1q) may also have an antithrombotic role.

Immunologic aspects of leprosy as related to leucocytic isoantibodies and platelet aggregating factors.

The incidences of various iso- and autoantibodies in a random population of 112 unselected leprosy patients is presented. Low titers of leucocytic isoantibodies and platelet aggregating factor were detected in the sera of a variable number of such patients. The leucoisoagglutinins were found in 8% of the sera of tuberculoid as well as lepromatous leprosy patients, whereas the leucoisocytotoxins were detected in a larger percentage of the lepromatous (40%) as well as tuberculoid (28%) cases. The platelet aggregating factors (PAF) were positive in 51.2% and 45% of lepromatous and tuberculoid cases respectively. Of the 21 positive sera for PAF, the antiplatelet factor by antihuman globulin consumption test could be demonstrated only in 66.6% and 50% of lepromatous and tuberculoid sera respectively. To study the frequencies of these newly detected antibodies or antibody-like factor and to compare their occurrences with other well-documented autoantibodies present in the sera of leprosy patients: cryoglobulins, antinucleoprotein antibody and thyroglobulin autoprecipitin were also studied in the sera of the same population of leprosy patients. It has been observed that the simultaneous occurrence of all these auto- and isoantibodies in the serum of one patient is a rare phenomenon. Leucocytic and platelet counts of these patients having antibodies against leucocytes and platelets were found to be within normal limits. Accordingly, it is suggested that the low levels of antileucocyte antibody and antiplatelet factor are probably harmless to the hosts. On the other hand, it is postulated that these antibodies may act as enhancing factors by being specifically adsorbed on the lymphoid cells, thus rendering them unresponsive to mitogenic stimulus in vitro. From these studies it seems that leprosy, especially the lepromatous type, is associated with some of the serological features suggestive of an autoimmune aberration.