Specific antibody uptake in tuberculosis?
Dear Sir, With interest we read the paper by Lee et al., entitled "Immunoscintigraphy in the detection of tuberculosis with radiolabeled antibody fragment against Mycobacterium boris bacillus Calmette-Gu6rin: a preliminary study in a rabbit model", dealing with specific targeting of tuberculous lesions [1]. Although their objectivedemonstration of specific antibody uptake in tuberculous infection-is attractive, we have encountered several problems with the presentation and especially the interpretation of the results: 1. It is not possible to induce a tuberculous infection with heat-killed Mycobacteriurn tuberculosis (BCG): what one induces is dead-BCG granulomas.
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It is not surprising that the antibody performs less well in the acute syphilis model (injection of antibody 10 days after inoculation) than in the subacute dead-BCG model (injection of antibody 6 weeks after inoculation). As we have shown previously, iodinated proteins do not show prolonged retention in acute infection due to the high turnover rate in these lesions [2,3]. In the acute syphilis model, one observes a relatively higher increase in vascular permeability, resulting in a high influx rate (initially high target to background ratios), but also a high efflux rate (relatively poor target to background ratios at later time points). The data reported by Lee et al. further emphasize the role of the radiolabel in imaging experimental infectious disease. Fundamental differences between indium-111 labelled and iodinated proteins both specific and non-specific antibodiescan be observed in the efflux rate out of the lesion due to the properties of the radiolabel after release from the protein [4][5][6]. For these reasons, conclusions on the performance of a specific antibody for subacute infection cannot be derived from comparison to an acute model.
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The authors confirmed the presence of antigen in the cytoplasm of histiocytes in the tuberculous lesions by immunohistochemical and acid-fast bacilli stains. However, their conclusion that antigen-antibody reaction is therefore an important factor in accumulation of the antibody is invalid since antibody-antigen interaction is not demonstrated. This can only be done with autoradiographic methods showing association of the radiolabel with the antigen. Even then, it remains to be proven that the intact radiolabel-antibody complex is actually bound to the antigen. Moreover, how do the authors explain specific targeting of intracytoplasmic antigen with large radiolabelled proteins?
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The non-specific control antibody shows even higher uptake in the BCG foci than the BCG-specific W i m J.G. Oyen z