Mycobacterium avium complex disease in patients with AIDS: seroreactivity to native and recombinant mycobacterial antigens

Abstract

Antibodies to Mycobacterium avium complex (MAC) antigens were measured by enzyme-linked immunosorbent assays and immunoblot analyses in sera from 20 patients with AIDS and disseminated MAC disease, 5 human immunodeficiency virus-seronegative patients with pulmonary MAC infections, and 20 healthy controls. Whereas enzyme-linked immunosorbent assay titers for healthy controls and patients with AIDS and MAC disease were comparable, human immunodeficiency virus-seronegative patients with MAC disease had higher anti-MAC antibody titers (P < 0.01). Immunoblot analysis with the same sonic extracts indicated that each of the three groups had a limited heterogeneous response to M. avium antigens. No significant differences in immunoblot reactivities were detected. However, immunoblot studies with recombinant nontuberculous mycobacterial antigens revealed that sera from over 90% of the patients with MAC disease and only 25% of controls recognized a recombinant protein derived from a 35-kDa mycobacterial antigen. Although sonic extracts did not permit adequate discrimination of antibody reactivity in patients with MAC disease, recombinant antigens mày be useful as indicators of disease. Mycobacterium avium-M. intracellulare complex (MAC) bacilli are common environmental organisms that are readily isolated from fresh and salt water, soil, and dust (11). Until recently, MAC disease was rare and generally seen only in patients with severe underlying conditions such as silicosis, emphysema, and Hodgkin's disease (9). However, in the past decade, the importance of MAC has increased dramatically primarily because of its association with AIDS (8, 14). Hospital-based estimates suggest that 30 to 50% of patients with AIDS develop MAC infections. M. avium is the most common bacterial isolate and the major cause of systemic bacterial infections in AIDS-afflicted individuals (31). As patients with AIDS live longer because of improved drug therapies, MAC bacteremia is expected to increasingly contribute to AIDS-related morbidity and mortality (15). The frequency of MAC disease is also increasing in the immunocompetent population. Prince et al. (22) have reported that MAC pulmonary infections are becoming a prevalent clinical problem in persons without predisposing conditions. In fact, non-AIDS-related pulmonary disease caused by MAC is as common as pulmonary tuberculosis in many areas of the United States. Currently, the clinical management of MAC disease is challenging. The MAC bacilli readily develop resistance to available tuberculosis medications. Combination chemotherapy with amikacin, ethambutol, rifampin, and ciprofloxacin can clear the MAC bacteremia. However, many patients fail to respond or relapse despite the multiple drug treatments (30). Furthermore, the detection and diagnosis of MAC disease is time-consuming and difficult. Standard culture methods, often essential for diagnosis, require several weeks for positive identification (26). Modern nucleic acid hybridization techniques are extremely specific but are not generally...

Nucleotide sequence analysis and serologic characterization of a 27-kilodalton Mycobacterium intracellulare lipoprotein

“…The high frequency of anti-MAC seroreactivity within the general population is probably a result of repeated colonization and transient infections of this environmental organism. The failure of AIDS patients to mount a generalized elevated humoral response to MAC infections is also consistent with observations reported in previous studies (3,21,42). Patients with AIDS have been shown to have impaired humoral responses to newly acquired infections and newly introduced antigens (20,35).…”

“…Antibodies reacting with MI43 were detected in sera from 80% of HIV-seronegative patients infected with the MAC, 90% of tuberculosis patients, 50% of patients with AIDS and MAC disease, and 40% of healthy controls. The reactivity of control sera against M. avium antigens has been reported previously (3,21,41). The high frequency of anti-MAC seroreactivity within the general population is probably a result of repeated colonization and transient infections of this environmental organism.…”

The Mycobacterium avium complex.

“…The antibody response of humans and mice to MAC infection, as judged by Western blots (immunoblots), is heterogeneous (36,343), and blot profiles from different patients show distinct individual patterns with a few predominant common bands. Like M. tuberculosis, M. avium releases a 65-kDa protein in response to the stress of increased temperature or exposure to acid pH (39).…”

Age-dependent humoral responses of children to mycobacterial antigens

“…Low levels of antibody to a variety of both general mycobacterial (2, 7) and specific MAC antigens have been detected in sera from healthy adults (4,24,38). Elevated antibody levels to MAC antigens have been found in sera from nonimmunocompromised patients with MAC pulmonary infections as well as patients with hairy cell leukemia who are also infected with DMAC (29,43,45). In contrast, AIDS patients infected with DMAC have universally low levels of antibody against MAC antigens in spite of their infection (4,29,44,45).…”