Normal magnetic resonance appearances of the temporomandibular joints in children and young adults aged 2-18 years.

BACKGROUND: Knowledge of normal appearances of the temporomandibular joint (TMJ) is paramount when assessing the joint for disease in juvenile idiopathic arthritis. Reliable features defining normal TMJs in children are limited. OBJECTIVE: To establish reliable normal standards for the TMJ at magnetic resonance imaging (MRI). MATERIALS AND METHODS: We included children and young adults aged 2-18 years undergoing a head MRI for reasons not believed to affect the TMJs. We assessed TMJ anatomy and contrast enhancement using a high-resolution 3-D T1-weighted sequence. We noted joint fluid and bone marrow oedema based on a T2-weighted sequence. Three experienced radiologists read all examinations twice in consensus and defined intraobserver consensus agreement. RESULTS: We evaluated the TMJs in 101 children and young adults (45 female), mean age 10.7 years (range 2-18 years). The intraobserver consensus agreement for the assessment of anterior condylar inclination in the sagittal/oblique plane was moderate to good (Cohen κ=0.7 for the right side). Cohen κ for intraobserver consensus agreement for condylar shape in the coronal plane on a 0-2 scale was 0.4 for the right and 0.6 for the left. Intraobserver agreement for measurement of joint space height and assessment of bone marrow oedema was poor. There was a statistically significant increase in anterior inclination by age in the sagittal plane on a 0-2 scale (P<0.0001). Eighty percent of the condyles showed a rounded shape in the coronal plane while 20% showed mild flattening. Thirty-five of 36 right TMJs showed contrast enhancement (mild enhancement in 32 joints, moderate in 3 joints). CONCLUSION: Subjective assessment of the anterior condylar inclination in the sagittal/oblique plane and condylar flattening in the coronal plane can be considered precise features for describing TMJ anatomy in healthy children. There is an increasing anterior inclination by age. Mild contrast enhancement of the TMJs should be considered a normal finding.

Association between circulating levels of the novel TNF family members APRIL and BAFF and lymphoid organization in primary Sjögren's syndrome.

B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are members of the tumour necrosis factor superfamily. We have examined circulating BAFF and APRIL in relation to serological deviations and lymphoid organization in the salivary glands of the chronic, autoimmune disorder Sjögren's syndrome. Lymphoid organization in the shape of ectopic germinal centers were detected in 33 of 130 consecutive minor salivary gland biopsies and coincided with increased focus score and elevated levels of serum IgG. Follicular dendritic cell networks, proliferation of mononuclear cells and altered B/T cell ratio also separated the two subgroups. Serum levels of sBAFF and sAPRIL were increased in Sjögren's syndrome compared to healthy blood donors, especially in anti-Ro/La+ patients. Though the differences could not be related to germinal center formation, positive correlations between serum levels of sBAFF and sAPRIL, focus score and IgG denotes their possible role in the disease progression of primary Sjögren's syndrome.

Programmed cell death of peripheral blood B cells determined by laser scanning cytometry in Sjögren's syndrome with a special emphasis on BAFF.

Functionally impaired B cells play an important role in the pathogenesis of Sjögren's syndrome (SS). The aim of the study was to investigate the apoptosis susceptibility of peripheral blood B cells from patients with SS and the impact of B cell activating factor (BAFF) on the apoptosis capability of these cells in correlation with IgG production. Peripheral blood B cells were isolated and stained for apoptosis markers (Bax, Bcl-2) and members of the TNF-R superfamily, CD95 and CD40. The apoptosis frequency of cells bearing these markers were assessed. Also, the apoptosis capability of cultured B-lymphocytes was investigated in medium alone, with anti-CD95 or with soluble BAFF. Quantitative ELISA was performed to detect plasma levels of sBAFF. Furthermore, the level of circulating B-cell cytokines was measured. BAFF levels were compared between patients with normal and elevated IgG levels. In SS, Bcl-2 positive B cell counts were significantly higher then in controls, also in this population the apoptosis frequency was reduced. Apoptosis within Bax+ and CD40+ B cells were significantly decreased in patients. BAFF induced a significant antiapoptotic effect in SS; also this effect was clearly evident in B cells from SS with hypergammaglobulinaemia. Plasma BAFF levels were significantly higher in SS, mostly in patients with hypergammaglobulinaemia. Plasma B-cell cytokines were raised in SS. In Sjögren's syndrome B cells, a general antiapoptotic tendency might lead to prolonged B-cell survival driven at least partly by elevated levels of BAFF and supposedly by B-cell cytokines. Also, the exaggerated BAFF stimulation might lead to excessive immunoglobulin production. The B-cell apoptosis defects, the increased BAFF levels-correlating with hypergammaglobulinaemia-together with the raised B-cell cytokine levels indicates the disturbed B-cell biology in the disease.

Programmed cell death in rheumatoid arthritis peripheral blood T-cell subpopulations determined by laser scanning cytometry.

Because peripheral blood mononuclear cells play an important role in the perpetuation of the autoimmune process in rheumatoid arthritis (RA) and because the maintenance of these cells might be caused by the dysregulation of apoptosis, we investigated the apoptosis susceptibility of peripheral blood mononuclear cells from patients with RA. Freshly separated peripheral blood lymphocytes were stained for apoptosis markers (CD95, Bax, Bcl-2, TNF receptor) and for an activation marker (CD45-RO), and the apoptosis frequency of cells bearing these markers were assessed by the terminal-deoxynucleotidyl transferase-mediated dUTP digoxigenin nick end labeling method and nuclear condensation analysis with laser scanning cytometry. Also, the ability of CD4(+) and CD8(+) T-cell populations to undergo apoptosis was investigated with 24-hour culture in medium alone or with different apoptosis inducers (anti-CD3, anti-CD95, anti-TNF receptor). Laser scanning cytometry analysis was used to enumerate the phenotype and apoptosis ratios of both freshly isolated and cultured lymphocytes. Quantitative ELISA was performed to detect plasma levels of TNF-alpha and soluble Fas ligand. Furthermore, we studied the relationship between marked apoptotic defects in patients with RA and the severity of clinical disease. CD4(+) T-cell counts in patients with RA were elevated compared with controls. A decreased rate of anti-CD95-mediated apoptosis was found within the CD4(+) and CD8(+) lymphocytic subpopulations. In patients with RA, decreased Bax expression and decreased apoptosis rate within the Bax-positive cells were found, whereas Bcl-2 expression was elevated. The CD45-RO expression was higher, whereas the apoptosis within CD45-RO(+) cells were decreased in RA. Evaluation of plasma soluble Fas ligand revealed significantly decreased levels in patients compared with controls. The reduced susceptibility to CD95-mediated apoptosis may contribute to the expansion of an activated CD4(+) lymphocyte subpopulation and thus to the maintenance of peripheral autoreactive T-cell clones in RA. We also revealed a relationship between in vitro demonstrated lymphocyte apoptosis defects and clinical disease activity.

Attenuated apoptosis of B cell activating factor-expressing cells in primary Sjögren's syndrome.

B cell activating factor (BAFF) is known to be a powerful regulator of B-cell differentiation and proliferation. The aim of this study was to assess the incidence of apoptosis among BAFF-expressing cells in Sjögren's syndrome (SS) salivary gland tissue. We performed double stainings of BAFF together with one of the markers, CD21, CD68, CD40, Fas, Bcl-2 or Bax, and monitored apoptosis among BAFF expressing cells by using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick-end labeling method. A significantly lower level of apoptosis among the BAFF-expressing cells was detected in salivary glands from patients with SS compared with controls (p = 0.03). Furthermore, no difference in the coexpression of Fas or CD40 together with BAFF was detected between patients and controls. Coexpression of the pro apoptotic molecule Bax together with BAFF was nonsignificantly decreased in patients with SS compared with controls. Our results suggest that a reduced level of apoptosis among BAFF-expressing cells might lead to longer-existing BAFF expression within these cells and thereby maintain signaling for tissue-infiltrating B cells to proliferate and mature.