Lymph node biopsy analysis reveals an altered immunoregulatory balance already during the at-risk phase of autoantibody positive rheumatoid arthritis.

The balance between proinflammatory and regulatory CD4+ T cells is tightly controlled in lymphoid organs. In autoimmune diseases this balance is altered in the periphery and target tissue of patients. However, not much is known about the balance initiated in lymphoid organs during the development of disease. Since systemic autoimmunity is present years before the clinical manifestations of rheumatoid arthritis (RA), it is possible to study the immunoregulatory balance during the earliest (preclinical) phases of disease. Here, we report for the first time the frequency and phenotype of proinflammatory and regulatory CD4+ T cells in lymph node biopsies obtained from autoantibody positive individuals at risk for developing RA, patients with established disease and healthy controls. The frequency of proinflammatory LN Th1 cells was increased in RA patients compared with HCs, while the frequency of regulatory T cells was lower in LN biopsies of RA-risk individuals. Upon in vitro stimulation LN CD4+ T cells produced lower levels of proinflammatory cytokines, IFN-γ and IL-17A, in both RA-risk individuals and early RA patients. This study shows that already during the earliest phases of systemic autoimmunity the immunoregulatory balance between proinflammatory and regulatory CD4+ T cells is altered in LN tissue.

Human lymph-node CD8(+) T cells display an altered phenotype during systemic autoimmunity.

Although many studies are focused on auto-reactive CD4(+) T cells, the precise role of CD8(+) T cells in autoimmunity is poorly understood. The objective of this study is to provide more insight into the phenotype and function CD8(+) T cells during the development of autoimmune disease by studying CD8(+) T cells in human lymph-node biopsies and peripheral blood obtained during the earliest phases of rheumatoid arthritis (RA). Here, we show that lymphoid pro-inflammatory CD8(+) T cells exhibit a less-responsive phenotype already during the earliest phases of autoimmunity compared with healthy individuals. We found an increase in CD8(+) memory T cells in lymphoid tissue during the earliest phases of autoimmunity, even before clinical onset of RA, accompanied by an increased frequency of non-circulating or recently activated (CD69(+)) CD8(+) T cells in lymphoid tissue and peripheral blood. Importantly, lymphoid pro-inflammatory CD8(+)IL-17A(+) T cells displayed a decreased capacity of cytokine production, which was related to disease activity in early RA patients. In addition, a decreased frequency of regulatory CD8(+)IL-10(+) T cells in peripheral blood was also related to disease activity in early RA patients. Our results suggest that different CD8(+) T-cell subsets are affected already during the earliest phases of systemic autoimmunity.

Blood volume measurement with indocyanine green pulse spectrophotometry: dose and site of dye administration.

BACKGROUND: (1) To determine the optimal administration site and dose of indocyanine green (ICG) for blood volume measurement using pulse spectrophotometry, (2) to assess the variation in repeated blood volume measurements for patients after subarachnoid hemorrhage and (3) to evaluate the safety and efficacy of this technique in patients who were treated for an intracranial aneurysm. METHODS: Four repeated measurements of blood volume (BV) were performed in random order of bolus dose (10 mg or 25 mg ICG) and venous administration site (peripheral or central) in eight patients admitted for treatment of an intracranial aneurysm. Another five patients with subarachnoid hemorrhage underwent three repeated BV measurements with 25 mg ICG at the same administration site to assess the coefficient of variation. FINDINGS: The mean +/- SD in BV was 4.38 +/- 0.88 l (n=25) and 4.69 +/- 1.11 l (n=26) for 10 mg and 25 mg ICG, respectively. The mean +/- SD in BV was 4.59 +/- 1.15 l (n= 26) and 4.48 +/- 0.86 l (n=25) for central and peripheral administration, respectively. No significant difference was found. The coefficient of variance of BV measurement with 25 mg of ICG was 7.5% (95% CI: 3-12%). CONCLUSIONS: There is no significant difference between intravenous administration of either 10 or 25 mg ICG, and this can be injected through either a peripheral or central venous catheter. The 7.5% coefficient of variation in BV measurements determines the detectable differences using ICG pulse spectrophotometry.

Interobserver variability in the detection of cerebral venous thrombosis using CT venography with matched mask bone elimination.

OBJECTIVES: Computed tomography venography (CTV) has proven to be a reliable imaging method in the evaluation of cerebral venous thrombosis with good correlation to magnetic resonance (MR) imaging and digital subtraction angiography (DSA). It is fast and widely accessible, especially in the emergency setting. For better visualization of vascular structures bone is often removed from the images. The purpose of this study was to evaluate the quality of a fully automatic bone removal method, matched mask bone elimination (MMBE), and to assess the interobserver variability of the CTV technique. PATIENTS AND METHODS: Fifty patients with clinical suspicion of cerebral venous thrombosis underwent multislice CTV with MMBE post-processing. Axial source images and maximum intensity projections were retrospectively evaluated by two neuroradiologists for quality of bone removal and for the presence or absence of thrombosis in nine dural sinuses and five deep cerebral veins. A per sinus/vein and a per patient analysis (thrombosis in at least one sinus or vein) was performed and interobserver agreement was assessed. RESULTS: Both observers considered bone removal good in all patients (100%). Interobserver agreement per patient was excellent (kappa=0.83), with a full agreement in 47 of 50 patients (94%). The interobserver agreement per sinus or vein was good (kappa=0.76), with a full agreement in 679 of 700 sinuses or veins (97%). CONCLUSION: CTV aided with MMBE is a robust technique for visualization of the intracranial venous circulation, removing bone effectively. CTV has high interobserver agreement for presence or absence of cerebral venous thrombosis.

Perfusion CT to evaluate the effect of transluminal angioplasty on cerebral perfusion in the treatment of vasospasm after subarachnoid hemorrhage.

INTRODUCTION: Delayed ischemic neurologic deficits secondary to vasospasm are a major cause of morbidity and mortality after subarachnoid hemorrhage (SAH). Treatment of vasospasm after SAH is associated with complications, and reliable techniques for evaluating effects of treatment of vasospasm in such patients are warranted. We present the use of perfusion computed tomography (PTC) to evaluate the effect of transluminal percutaneous angioplasty in a with SAH and vasospasm-induced ischemia. METHODS: Dynamic PCT with deconvolution produced maps of time-to-peak, mean transit time, regional cerebral blood flow, and regional cerebral blood volume, with a computerized automated map of the infarct and penumbra. CT scanners with quadruple detector array were used before and after angioplasty. RESULTS: Before angioplasty and intraarterial papaverine, PCT showed normal to decreased cerebral blood flow and increased cerebral blood volume and mean transit time in the middle cerebral artery territory of the left hemisphere. After angioplasty and intraarterial papaverine, PCT showed normalization of perfusion parameters. CONCLUSION: PCT can be a useful technique in monitoring angioplasty treatment effects in patients with vasospasm after SAH.