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A major aspect of the adaptive host response in periodontitis is the production of antibodies. Several risk and susceptibility factors for periodontitis, including smoking, age and composition of the subgingival microflora, have also been suggested to influence antibody production.The present study was conducted to investigate plasma levels of immunoglobulin (Ig) G, A and M antibodies in periodontitis patients of Caucasian European heritage in relation to disease severity, smoking, diagnosis and prevalence of periodontopathogens.In this study, 29 patients with severe periodontitis, 51 with moderate periodontitis and 55 controls without periodontal destruction were enrolled. From the total of 80 patients, 18 were diagnosed with aggressive periodontitis and 62 with chronic periodontitis. Total IgG, IgA and IgM as well as IgG isotypes were analyzed in plasma samples.Levels of total IgG, IgA and IgM were not different between patients and controls; however, in periodontitis, higher levels of IgG1 and IgG2 were observed. Smoking appeared to be significantly and inversely related to antibody levels in periodontitis, in particular for total IgG and IgG2. The absence of an elevated total IgG and IgG2 in smoking patients was irrespective of severity, prevalence of periodontal pathogens and diagnosis. The elevation of total IgG and IgG1 and IgG2 in non-smoker periodontitis patients was observed in patients with moderate periodontitis and even greater in patients with severe periodontitis, but was independent whether patients were infected with Actinobacillus actinomycetemcomitans or Porphyromonas gingivalis and independent of diagnosis. Clinically, it was observed that patients who smoked had more periodontal bone loss; the current findings on antibody levels may be one of several mechanisms related to more extensive periodontal breakdown in smoker patients.The current study shows that non-smoker periodontitis patients have higher levels of total IgG and IgG2 than smoker periodontitis patients.