CXCL13 and CCL21 have been functionally implicated in lymphoid tissue organization both in the upstream phases of lymphoid tissue embryogenesis and in ectopic lymphoid neogenesis in transgenic mice. Here, we analyzed the relationship between CXCL13 and CCL21 production and lymphoid tissue organization in rheumatoid synovitis as a model of a naturally occurring ectopic lymphoneogenesis. Through systematic analysis of mRNA and protein expression, we defined the microanatomical relationship between CXCL13 and CCL21 in progressive aggregational and structural phases of synovial inflammatory infiltrate. We provide the first direct in situ evidence that production of CXCL13 and CCL21 (rather than simply protein binding) is associated with inflammatory lymphoid tissue formation and development with the demonstration, in organized aggregates, of a secondary lymphoid organ-like compartmentalization and vascular association. Notably, the presence of CXCL13 and CCL21 (protein and mRNA) was also demonstrated in non-organized clusters and minor aggregational stages, providing evidence that their induction can take place independently and possibly upstream of T-B compartmentalization, CD21 + follicular dendritic cell network differentiation and germinal center formation. Our data support the concept that, under inflammatory conditions, CXCL13 and CCL21 participate in lymphoid tissue microanatomical organization, attempting to recapitulate, in an aberrant lymphoid neogenetic process, their homeostatic and morphogenetic physiologic functions.

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Fusobacterium nucleatum is an anaerobic bacillus of oro-pharyngeal origin. We describe a case of two manifestations of fusobacterium-induced sepsis originating from an asymptomatic dental root abscess. CASE HISTORY A 63-year-old Caucasian man presented to the accident and emergency department with a 2-week history of night sweats, anorexia, 6 kg weight loss and lumbo-sacral back pain radiating to the right buttock and thigh. In addition, he had been intermittently confused and drowsy over the previous 48 hours. Other than gout and osteoarthritis there was no significant past medical history. On examination, he was apyrexial but tachycardic, with normal cardiac sounds and no peripheral stigmata of infective endocarditis. There was no focal spinal tenderness or nuchal rigidity and neurological examination was normal apart from significantly diminished straight leg raise on the right. Laboratory tests showed raised inflammatory markers (C-reactive protein [CRP] 402 mg/L, normal range [NR]510; erythrocyte sedimentation rate [ESR] 84 mm in first hour), leucocytosis, (total white cell count [WCC] 27.5 with neutrophils 23.1Â10 9 /L) and deranged liver function (alkaline phosphatase 282 IU/L, NR5125; AST 53 IU/L, NR540; LDH 225 IU/L, NR5180). Serial blood cultures, myeloma screen, tumour markers, X-ray of the chest and lumbo-sacral spine, abdominal ultrasound and electrocardiogram were negative or normal. Magnetic resonance imaging of the lumbar spine showed discitis of L4/L5. This disc was subsequently aspirated under computed tomography guidance prior to commencement of empirical antibiotic therapy with intravenous fluclox-acillin and oral Fucidin (sodium fusidate). Forty-eight hours later the patient became acutely confused with signs of acute urinary retention and bilateral lower limb hypertonia and hyperreflexia. Plantar responses were flexor and muscle power normal; sensation was difficult to assess. Repeat blood tests demonstrated a rise in neutrophil count to 32.9Â10 9 /L and acute renal failure with urea 24.1 mmol/L and creatinine 409 mmol/L.

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