Non-familial multiple keratoacanthomas in a 70 year-old long-term non-progressor HIV-seropositive man.

We describe here multiple keratoacanthomas in an Human Immunodeficiency Virus (HIV)-seropositive 70 year-old man. The patient had multiple epithelial tumors of the skin showing rapid growth, histopathological features of a keratoacanthoma and a conspicuous tendency toward spontaneous remission. A diagnosis of nonfamilial multiple keratoacanthoma was established. The patient had a CD4 count of 633 cells/microL. The HIV disease in our patient was of a nonprogressive nature with CCR5-positive T cells.

B-cell immune responses in HIV positive and HIV negative patients with tuberculosis evaluated with an ELISA using a glycolipid antigen.

The diagnostic value of the PGL-Tb1 enzyme-linked immunosorbent assays (ELISA) was established following a survey study using sera from 220 Tuberculosis patients (including 69 HIV coinfected) and 324 controls. A higher percentage (76.8%) of the HIV-seropositive compared to the HIV-seronegative (58.9%) TB patients were ELISA positive (p=0.02) with a specificity of 94%. In HIV-positive TB patients, ELISA sensitivity was identical for all sites of disease and antibody levels were not affected by the CD4+ counts, PPD results, age or bacterial yield. Combining data for both the smear microscopy and ELISA maximized sensitivity. The kinetics of anti-PGL-Tb1 antibody was evaluated in cohort studies using sera collected before, during and after treatment for clinical TB for 79 TB patients (including 39 HIV coinfected). Statistically significant ELISA signals were observed in 51.3% of HIV-seropositive TB patients prior to the diagnosis of clinical TB and elevated antibody levels persisting 18 months after the end of antituberculous chemotherapy. Asymptomatic development of antibody also occurred in 22.7% of a cohort of 44 HIV-positive patients with a high risk of tuberculosis, but no correlation was found between persisting elevated antibody levels and progression to active disease. This antibody response in absence of disease, might reflect the control of an incipient tuberculosis infection by antituberculous prophylaxis or through an improved protective immune response associated with antiretroviral therapy.

DC-SIGN association with the Th2 environment of lepromatous lesions: cause or effect?

The clinical spectrum of leprosy is related to patients' immune responses. Non-responsiveness towards Mycobacterium leprae (ML) seems to correlate with a Th2 cytokine profile. The reason for such a polarized immune response remains unclear. The C-type lectin, DC-SIGN, expressed by subsets of dendritic cells (DCs) and macrophages, has previously been associated with Th2 responses. Here we show abundant DC-SIGN expression in lepromatous but not borderline tuberculoid leprosy, in both HIV-positive and HIV-negative patients. Moreover, we demonstrate that DC-SIGN can act as an entry receptor for ML, as it does for M. tuberculosis, through the cell wall component lipoarabinomannan. DC-SIGN is expressed on virtually all ML-containing cells, providing further evidence for its role as a receptor. DC-SIGN may therefore be induced on macrophages in lepromatous leprosy and may then contribute to mycobacterial entry into these cells.

Leprosy reversal reaction in HIV-positive patients.

We report two cases of leprosy in HIV-infected patients who, by their clinical, histological and immunological features, enhance the evidence that HIV-positive leprosy does not differ from nonHIV-positive leprosy. Moreover, extensive studies of reversal reactions in HIV-positive patients might be of great interest in determining the exact pathogenesis of this leprosy reactional state.

Clinical usefulness of serological measurements obtained by antigen 60 in mycobacterial infections: development of a new concept.

The humoral immune response occurring during mycobacterial infections was analysed with an ELISA test based on antigen 60. With tuberculosis, IgM antibodies indicate a primo-infection or a process of reactivation while IgG determinations allow an evaluation of the intensity of the infectious process. The test is also applicable to extrapulmonary tuberculosis, provided its sensitivity be adapted to these particular cases. This is particularly clear for tuberculous meningitis. The test is not species-specific and allows the detection of antibodies in atypical mycobacterioses and in leprosy patients. The final differentiation must be done by clinical examinations and cultures. In leprosy patients, IgM antibodies are detected nearly as frequently as IgG antibodies. In HIV-seropositive patients, the A60 seropositivity is correlated with a reactivation of former tuberculous infections and with primary tuberculous infections. At the AIDS stage, the A-60 seropositivity is due to atypical mycobacteria, with a better IgM than IgG response. Healthy people are negative in serology: the positive cases observed are due to inapparent infections gained by contact with an infectious focus. The seropositive cases observed in non-tuberculous hospitalized patients are restricted to some disease types, essentially lung infections (cystic fibrosis, cancer pneumopathies, sarcoidosis). Some patients have low levels of antibodies. This anergy may be traced to the formation of immune complexes or else to a weak avidity of the specific antibodies produced. This test should not be considered to be a diagnostic tool by itself. It should be used in conjunction with other diagnostic means that, together, allow the determination of a diagnosis.

Distribution of antibodies against denatured collagen in AIDS risk groups and homosexual AIDS patients suggests a link between autoimmunity and the immunopathogenesis of AIDS.

Autoimmunity often precedes the onset of AIDS-related complex or AIDS, and a number of autoantibodies have been described in AIDS patients and persons at risk for AIDS. The presence of such antibodies provokes speculation that autoimmunity is a component of AIDS pathogenesis. We report evidence of an autoantibody (anticollagen) common to all homosexual AIDS patients studied. High titer serum reactivity against collagen was detected in all homosexual AIDS patients, and in HIV+ homosexuals (66%), HIV+ i.v. drug users (38%) HIV- homosexuals (32%), HIV+ transfusion recipients (22%), and HIV+ hemophiliacs (13%), but not in HIV- i.v. drug users, HIV- transfusion recipients, HIV- hemophiliacs, rheumatoid arthritis patients, or controls. Anticollagen reactivity does not correlate with serum IgG levels, so it is not merely a reflection of polyclonal B-cell activation. Titration of anticollagen positive sera typically revealed anticollagen antibody titers 100 times those of normal sera. Affinity purification and immunoblot analysis confirmed the antibody nature of the anticollagen reactivity. The anticollagen antibodies react preferentially with primary determinants of types I and III collagen revealed after heat denaturation. Similar antibodies occur infrequently in rheumatoid arthritis patients, more often on SLE, and frequently in graft vs host disease and lepromatous leprosy. Levels of anticollagen activity in HIV+ i.v. drug users and transfusion recipients correlate with serum beta 2-microglobulin levels, suggesting that those persons with anticollagen antibodies are at greater risk of developing AIDS. This correlation, the fact that anticollagen antibodies occurred in all homosexual AIDS patients tested, and the occurrence of antibodies against denatured collagen in immune disorders with features similar to AIDS suggest these antibodies may be related to disease progression. The association of anticollagen autoantibodies with AIDS and certain other infections and immune disorders may reflect common immunopathogenic features in the etiology of these disorders.