High titers of antinuclear antibody and the presence of multiple autoantibodies are highly suggestive of systemic lupus erythematosus.

The aim of this study is to evaluate the relationship between antinuclear antibody (ANA) titer and specificity, as well as the relationship between the number of positive-autoantibodies (AAbs) in antinuclear antibodies (ANAs) and specificity for systemic lupus erythematosus (SLE), so as to explore their significance in the diagnosis of SLE. A total of 1297 patients with ANA results was enrolled in this study, including 148 patients with SLE patients. The sensitivity, specificity, sensitive likelihood ratio and specific likelihood ratio of indicators in SLE were determined by receiver-operator characteristic (ROC) curve after measurement of ANA and ANAs by indirect immunofluorescence (IIF) and immunoblotting, respectively. ROC analysis showed that the specificity of ANA titer ≥ 1 +, ≥ 2 + and ≥ 3 + for SLE was estimated to be 81.29%, 90.69% and 96.52% respectively, with a increased titer-specific likelihood ratio (5.16, 9.29 and 19.60, respectively). The specificity of the number of positive-AAbs ≥ 1, ≥ 2 and ≥ 3 in ANAs for SLE was estimated to be 80.42%, 94.95% and 99.3% respectively, with a increased number-specific likelihood ratio (4.8, 15.26 and 72.48, respectively). The estimated sensitivity of the number of positive-AAbs ≥ 3, AnuA and anti-rRNP was higher than that of anti-Sm (p < 0.01) (50.68%, 41.89% and 31.76% vs. 16.89%, respectively), while there was no significant difference in their specificity (99.3%, 99.74% and 99.56% vs. 99.74%, respectively) (p > 0.05). High titers of ANA and the presence of multiple AAbs in ANAs are highly specific for SLE and highly suggestive of SLE. The likelihood of SLE can be assessed by ANA titer and the number of positive-AAbs in ANAs.

Clinical characteristics of autoimmune GFAP astrocytopathy.

The clinical features of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy remain to be elucidated. We describe here the clinical features of 14 patients with GFAP astrocytopathy confirmed by detection of GFAP-IgG in cerebrospinal fluid (CSF). The novel findings of this study are as follows. First, over half of the patients presented with movement disorders (tremor, myoclonus, and ataxia), autonomic dysfunction (mainly urinary dysfunction), and hyponatremia. Second, most patients showed transient elevation of adenosine deaminase activity levels in CSF. Finally, some patients showed bilateral hyperintensities in the posterior part of the thalamus on brain magnetic resonance imaging.

Evidence for the role of mast cells in colon-bladder cross organ sensitization.

This study examined the contribution of mast cells to colon-bladder cross organ sensitization induced by colon irritation with trinitrobenzene sulfonic acid (TNBS-CI). In urethane anesthetized rats 12 days after TNBS-CI, the voiding interval was reduced from 357 s to 201 s and urothelial permeability, measured indirectly by absorption of sodium fluorescein from the bladder lumen, increased six-fold. These effects were blocked by oral administration of ketotifen (10 mg/kg, for 5 days), a mast cell stabilizing agent. TNBS-CI in wild type mice produced a similar decrease in voiding interval (from 319 s to 209 s) and a 10-fold increase in urothelial permeability; however this did not occur in KitªWª/KitªW-vª mast cell deficient mice. Contractile responses of bladder strips elicited by Compound 48/80 (50 µg/ml), a mast cell activating agent, were significantly larger in strips from rats with TNBS-CI (145% increase in baseline tension) than in control rats (55% increase). The contractions of strips from rats with TNBS-CI were reduced 80-90% by pretreatment of strips with ketotifen (20 µM), whereas contractions of strips from control animals were not significantly changed. Bladder strips were pretreated with SLIGRL-NH2 (100 µM) to desensitize PAR-2, the receptor for mast cell tryptase. SLIGRL-NH2 pretreatment reduced by 60-80% the 48/80 induced contractions in strips from rats with TNBS-CI but did not alter the contractions in strips from control rats. These data indicate that bladder mast cells contribute to the bladder dysfunction following colon-bladder cross-sensitization.

Bone marrow-derived cells are sufficient and necessary targets to mediate glomerulonephritis and vasculitis induced by anti-myeloperoxidase antibodies.

Clinical and experimental evidence indicate that ANCA cause pauci-immune necrotizing and crescentic glomerulonephritis (NCGN) and systemic small vessel vasculitis in humans. One of the major target antigens for ANCA is myeloperoxidase (MPO). An animal model that closely resembles the human disease is induced by intravenous injection of anti-MPO IgG into mice. The likely primary pathogenic targets for the anti-MPO IgG are circulating neutrophils and monocytes, although other cells have been implicated, including endothelial cells and epithelial cells. Herein is reported a new model for anti-MPO-mediated glomerulonephritis and vasculitis that further documents the pathogenic potential of ANCA and demonstrates that bone marrow (BM)-derived cells are sufficient targets to cause anti-MPO disease in the absence of MPO in other cell type. MPO knockout (Mpo-/-) mice that were immunized with mouse MPO were exposed to irradiation and received a transplant of Mpo+/+ or Mpo-/- BM. Engraftment in mice with circulating anti-MPO resulted in development of pauci-immune NCGN in all mice and pulmonary capillaritis and splenic necrotizing arteritis in some. Anti-MPO IgG also was introduced intravenously into chimeric mice by transplantation of Mpo+/+ BM into irradiated Mpo-/- mice or Mpo-/- BM into irradiated Mpo+/+ mice. Chimeric Mpo-/- mice with circulating MPO-positive neutrophils developed NCGN, whereas chimeric Mpo+/+ mice with circulating MPO-negative neutrophils did not, thereby indicating that BM-derived cells are not only sufficient but also necessary for induction of anti-MPO disease. This novel animal model further documents ANCA IgG interactions with neutrophils as a cause of ANCA-associated glomerulonephritis and vasculitis.

Serum C-reactive protein concentration and lower urinary tract symptoms in older men in the Third National Health and Nutrition Examination Survey (NHANES III).

BACKGROUND: Inflammatory infiltrates are frequently found in and around nodules in benign prostate hyperplasia (BPH). We examined cross-sectionally the association of serum C-reactive protein concentration, a non-specific marker of inflammation, and lower urinary tract symptoms (LUTS), suggestive of BPH. METHODS: We included 2,337 men, 60 years and older, who participated in the Third National Health and Examination Survey (NHANES III) between 1988 and 1994. As part of NHANES III, serum C-reactive protein concentration was measured and men reported whether they currently experienced nocturia, incomplete emptying, hesitancy, or weak stream as well as whether they had had non-cancer prostate surgery in the past. All results were weighted to account for sampling probability in NHANES III. RESULTS: Age-adjusted and weighted mean serum C-reactive protein concentration was 0.32 mg/dl in men without symptoms and without surgery, 0.35 mg/dl in men with three or four symptoms (P = 0.06), and 0.36 mg/dl in men with one or two symptoms (P = 0.06). After adjusting for age and race and excluding men with an acute infection, men with a C-reactive protein concentration above the limit of detection (>0.30 mg/dl) were 1.47 times (95% CI 0.87-2.50) more likely to have three or four symptoms than men with a C-reactive protein concentration below the detection limit, although the association was not statistically significant. The association was not attenuated after adjusting for the metabolic syndrome, but was attenuated after excluding men with metabolic syndrome. CONCLUSIONS: These results suggest that elevated circulating C-reactive protein concentration might be an indicator of intraprostatic inflammation in symptomatic BPH. The presence of the metabolic syndrome might be a mediator of this association.