Human Memory B Cells in Healthy Gingiva, Gingivitis, and Periodontitis.

The presence of inflammatory infiltrates with B cells, specifically plasma cells, is the hallmark of periodontitis lesions. The composition of these infiltrates in various stages of homeostasis and disease development is not well documented. Human tissue biopsies from sites with gingival health (n = 29), gingivitis (n = 8), and periodontitis (n = 21) as well as gingival tissue after treated periodontitis (n = 6) were obtained and analyzed for their composition of B cell subsets. Ag specificity, Ig secretion, and expression of receptor activator of NF-κB ligand and granzyme B were performed. Although most of the B cell subsets in healthy gingiva and gingivitis tissues were CD19(+)CD27(+)CD38(-) memory B cells, the major B cell component in periodontitis was CD19(+)CD27(+)CD38(+)CD138(+)HLA-DR(low) plasma cells, not plasmablasts. Plasma cell aggregates were observed at the base of the periodontal pocket and scattered throughout the gingiva, especially apically toward the advancing front of the lesion. High expression of CXCL12, a proliferation-inducing ligand, B cell-activating factor, IL-10, IL-6, and IL-21 molecules involved in local B cell responses was detected in both gingivitis and periodontitis tissues. Periodontitis tissue plasma cells mainly secreted IgG specific to periodontal pathogens and also expressed receptor activator of NF-κB ligand, a bone resorption cytokine. Memory B cells resided in the connective tissue subjacent to the junctional epithelium in healthy gingiva. This suggested a role of memory B cells in maintaining periodontal homeostasis.

Elevated levels of a disintegrin and metalloproteinase 8 in gingival crevicular fluid of patients with periodontal diseases.

BACKGROUND: A disintegrin and metalloproteinase 8 (ADAM8) is involved in inflammation and is essential for osteoclastogenesis. Elevated ADAM8 levels are detected in human serum and other body fluids in several inflammatory conditions. Therefore, we hypothesized that ADAM8 levels are also raised in gingival crevicular fluid (GCF) of patients with periodontal diseases. METHODS: Forty-five patients with periodontal diseases (n = 15 for each group: the group of patients with gingivitis, the group with aggressive periodontitis [AgP], and the group with chronic periodontitis [CP]) and 15 volunteers who exhibited healthy gingiva were recruited. Four periodontal parameters, gingival index, plaque index, probing depth, and clinical attachment level, were recorded before GCF collection. The presence of ADAM8 in GCF was shown by immunoblotting using anti-human ADAM8 polyclonal antibody against its prodomain, and the ADAM8 levels were measured by an enzyme-linked immunosorbent assay. RESULTS: Four immunoreactive bands at 120, 70, 50, and <30 kDa were detected in the groups of patients with periodontitis, whose intensities were stronger than those in the group of patients with gingivitis, consistent with significantly greater ADAM8 levels in both groups of patients, with either CP or AgP, than those in the group of patients with gingivitis and in the group that was healthy (P <0.001). Moreover, the ADAM8 levels correlated significantly with the four periodontal parameters (P <0.001), indicating that ADAM8 levels are positively associated with the degree of periodontal tissue inflammation and destruction. CONCLUSIONS: The ADAM8 levels are elevated in the GCF of patients with periodontal diseases, including gingivitis, CP, and AgP, in comparison to control participants who are healthy, and they correlate with four clinical parameters that reflect the degree of disease severity.

Long-term survival in infantile malignant autosomal recessive osteopetrosis secondary to homozygous p.Arg526Gln mutation in CLCN7.

Infantile malignant autosomal recessive osteopetrosis (ARO; OMIM 259700) has been reported to be associated with mutations in TCIRG1, CLCN7, or OSTM1. ARO caused by homozygous (or compound heterozygous) mutations in CLCN7, as described here, is usually diagnosed at birth or early in infancy due to generalized osteosclerosis and severe hematologic deficits. The maximal life expectancy of patients with ARO in the absence of bone marrow transplantation is thought to be 10 years. We report on a 25-year-old Thai man who is affected with ARO. Clinical features include proportionate short stature, vision impairment, esotropia, exophthalmos, mild hearing loss, and hepatosplenomegaly. Pancytopenia was present and the patient had frequent illnesses. Radiographs showed generalized osteosclerosis with almost no visible of bone marrow spaces. Dense maxilla and mandible with impacted and malformed teeth were observed. Multiple fractures were reported. He developed osteomyelitis of the mandible on four separate occasions, and partial mandibulectomy was performed. Molecular studies showed that there were no pathogenic mutations in TCIRG1. However, mutation analysis of CLCN7 revealed a homozygous missense mutation (p.Arg526Gln). This patient is, it appears, the longest lived individual with ARO ever reported. Evaluation of osteoclastogenesis in our patient demonstrated very large immature osteoclasts with a high number of nuclei.