Detection of IgA subclasses and J chain mRNA bearing plasma cells in human dental periapical lesions by in situ hybridization.

Humoral immune responses are implicated in the pathogenesis of human dental periapical lesions. To elucidate whether IgA-associated immune systems play a role in the lesions, the in situ hybridization technique was used to detect J chain mRNA expression, which is correlated with the secretion of dimeric IgA. In addition, IgA subclass mRNA-expressing cells were also investigated by double target in situ hybridization (ISH) methodology using digoxigenin- and biotin-labeled IgA subclass specific oligonucleotide probes. This double target ISH technique involved immunochemical detection with an alkaline phosphatase-conjugated antibody and a peroxidase conjugated avidin-biotin complex system to detect IgA subclass mRNA in the formalin-fixed, paraffin wax embedded periapical tissue sections. Twenty-four biopsy samples (16 periapical granulomas and 8 radicular cysts) were examined. IgA subclass mRNA positive plasma cells were detected in all samples. IgA1 mRNA-expressing cells were predominant both in granulomas and cysts (mean = 75.3 +/- 11.2%, 64.8 +/- 21.3%, respectively), and the IgA1 proportion was higher in granulomas than in cysts, although no significant difference was seen between the two lesions (p = 0.132). J chain mRNA positive cells were very sparsely detected in 21/24 cases. The median percentages of J chain mRNA positive cells/IgA mRNA positive plasma cells (4.7%, range 0.3-13.6%) in cysts were significantly higher than in granulomas (1.3%, range 0-7.7%; p = 0.03). This result supports the hypothesis that dimeric IgA may be more actively produced in radicular cysts than in granulomas. These features are thought to reflect the local activation of the periapical immune system in response to environmental factors and indicate that secretory IgA mediated immune defense systems appear to play little role in these lesions. Our results indicate that the IgA-associated immune response in periapical lesions is more similar to serum or systemic IgA responses than to mucosa-associated immune responses where dimeric IgA predominates.