Lysosomal membrane protein 2 (LAMP-2) is a target of antineutrophil cytoplasmic autoantibodies (ANCA) in addition to the more commonly known targets proteinase 3 and myeloperoxidase. The prevalence of anti-LAMP-2 antibodies and their relationship to disease in ANCA glomerulonephritis are not well described. We measured anti-LAMP-2 reactivity in 680 sera samples (two academic centers) from patients with ANCA glomerulonephritis (n=329); those with ANCA-negative glomerulonephritis (n=104); those with fimbriated, gram-negative Escherichia coli urinary tract infection (n=104); disease controls (n=19); and healthy volunteers (n=124). With levels in healthy controls used to define a reference range, anti-LAMP-2 reactivity was present in 21% of ANCA sera from two of the centers; reactivity was present in 16% of the control group with urinary tract infection. Western blotting and immunofluorescence microscopy did not verify positivity. Titers of anti-myeloperoxidase and anti-proteinase 3 antibodies were 1500-fold and 10,000-fold higher than anti-LAMP-2 titers, respectively. There was no correlation between anti-LAMP-2 antibodies and disease activity. Furthermore, Wistar Kyoto rats injected with anti-LAMP-2 antibodies did not develop glomerulonephritis. In conclusion, antibodies that react with LAMP-2 may exist at very low titers in a minority of patients with ANCA disease. These data do not support a mechanistic relationship between anti-LAMP-2 antibodies and ANCA glomerulonephritis.

Data derived from periodontitis patients have provided support for a relationship between the distribution of selected members of the periodontopathic microbiota and antibody levels to the intact bacteria in both serum and GCF. These data are consistent with the systemic antibody as a reflection of the host response to an infectious process associated with an episode of disease activity. The purpose of this report is to address the concept that the host antibody responses may help to elucidate the specific etiologic agents and be used to model the risk for future periodontal disease progression in recurring periodontitis. These findings from one study in adult periodontitis patients indicated that elevations in certain antibody specificities are most closely associated with patients exhibiting a risk of disease recurrence. Furthermore, analysis of the frequency of antibody elevations suggested that patients capable of maintaining elevated antibody to these pathogens post-treatment, may be indicative of an individual at less risk. A 2nd investigation was implemented to address questions concerning host-parasite interactions in A. actinomycetemcomitans-associated recurring periodontitis. The results showed distinctive characteristics of local and systemic antibody responses and A. actinomycetemcomitans infection in patients with varying extents of recurrent disease. These longitudinal studies developed evidence for the potential of local and/or systemic antibody responses as indicators of periodontal disease recurrence.

Longitudinal investigations concerning immunological responses and periodontal disease activity support a relationship between serum antibody levels and the micro-organisms associated with dental plaque. To define this host response further, we studied the relationship of antibody avidity to Actinobacillus actinomycetemcomitans (Aa) in 11 adult periodontitis and 6 localized juvenile periodontitis (LJP) patients with Aa infections. Patients were monitored every 3-4 months for immunological and clinical variables including probing pocket depths (PD), bleeding on probing (BOP), plaque index (PLI), and the number of disease active sites (DA). Avidity indices were determined using an ELISA and significant changes from each patients' baseline level were determined. The results showed different response patterns between and within the patient groups. A subset of the subjects experienced significant changes in antibody avidity over time. Between group comparisons yielded no significant differences in the number of positive or negative avidity index changes, although there were more frequent changes in the disease active adult periodontitis group. There were also no significant correlations between clinical parameters and antibody avidity, although there were changes in the clinical parameters between baseline and significant avidity change points, and also between baseline and the determination of active disease. Further studies will be necessary to define fully the role of antibody avidity and its relationship to the pathogenesis of periodontal diseases.

SUMMARYWe designed a study to examine the serum IgG antibody avidity characteristics in: (i) normal subjects (N); (ii) Actinobacillus actinomycetemcomitans-infected adult periodontitis (AP Aa+); (iii) A. actinomycetemcomitans-infected localized juvenile periodontitis (UP Aa+); and (iv) AP subjects (AP) with various antibody patterns and disease presentation. Although there were significant elevations in antibody levels for AP Aa+ and UP Aa+ patients compared with AP and normal patients (P < 0'0001), there were no significant differences in the avidity indices (AI). Correlations of antibody levels to avidity revealed that functional activity of the antibody as measured by avidity was independent of antibody levels. Increasing antibody levels correlated with an increase in the number of infected sites, yet there was a trend for AI to decrease with increased infection. Avidity indices for all patient groups did not appear to show a strong biologic relationship to plaque; however, in AP Aa+ and UP Aa+ patients there was a generally positive relationship between avidity and bleeding on probing or pocket depth. In AP Aa+ and UP Aa+ patients, and in AP patients there was a positive relationship of avidity through a threshold of ::::::8 active disease sites. This study hypothesized that antibody avidity to A. actinomycetemcomitans could help to explain the relationship between the active host response and chronic infection with this pathogen. The results provide evidence that both antibody levels and avidity may contribute to the variation in host resistance to infection and disease associated with A. actinomycetemcomitans.