Long term prognosis of children born to lupus patients

OBJECTIVE: To determine the long term prognosis of children of patients with systemic lupus erythematosus (SLE). METHODS: Children of patients with SLE were invited to attend our clinic for physical examination and laboratory tests. A total of 195 children (aged 4 months to 26 years; male = 82, female = 113) were examined in 1991, 1995, 1997, and 1998. RESULTS: Two cases were diagnosed as SLE at the first visit and were excluded from the second visit. A significantly higher percentage (52/195 (27%)) of patients were positive for antinuclear antibodies (ANA) at a cut off serum dilution of 1/40 compared with controls (4/57 (7%)). ANA were detected more frequently in female subjects than in men (p<0.05). Forty four subjects were examined on more than two occasions. Nine of the 10 patients who were positive for ANA at the second visit were girls aged 4-8 years. The incidence of anti-DNA and antiphospholipid antibodies in children of patients with SLE was similar to that in the controls. CONCLUSIONS: The finding that children, especially girls, born to maternal lupus patients had a high positive rate for ANA suggests that a genetic factor is involved in SLE pathogenesis. Longitudinal observation of these patients may provide important clinical information and clues to the pathogenesis of SLE.     

Enhancement of the action of colony stimulating factor (CSF) by soluble component(s) of erythrocytes in mouse bone marrow cells cultures.

Rat erythrocytes, separated from other blood cells by SE-cellulose chromatography, were lysed by exposure to hypotonic solution, dialyzed and ultracentrifuged. The supernatant contained a substance which enhanced the activity of colony stimulating factor (CSF) in soft agar cultures of granulocyte-macrophage progenitor cells (CFU-C) from normal mouse bone marrow. The growth-enhancing effect of the erythrocyte factor was observed when mouse L-cell conditioned medium was used as the CSF source and also when serum from endotoxin-treated mice or from mice undergoing graft-versus-host reaction was used as the stimulant. The erythrocyte factor effect was also detected by 3H-thymidine uptake of bone marrow cells in liquid cultures. These results suggest that the effect of the erythrocyte factor on CSF is not restricted to CSF from a specific source nor to semi-solid agar cultures.     

The ratio of neutrophils to lymphocytes and the phenotypes of neutrophils in patients with early gastric cancer

We examined 55 patients (40 male, 15 female) who were diagnosed from 1987 to 1991 as having early gastric cancer (EGC) stage I according to the general rules of classification of the Japanese Research Society for Gastric Cancer. Of the 55 patients, 42 (30 male, 12 female) were alive in April 1992. The prognosis correlated well with the ratio of neutrophils to lymphocytes (N/L ratio) but not with the total number of white blood cells in the peripheral blood. The patients were divided into two groups according to their N/L ratio. Of the 29 patients with an N/L ratio less than 2, 27 were alive in 1992, whereas only 15 of the 26 patients with an N/L ratio of 2 or more were alive (χ² analysis, P = 0.0022). We further examined the phenotypes of neutrophils from 29 other patients with EGC at the time of diagnosis before surgical operation. These patients were divided into two groups: 17 patients with a low N/L ratio (less than 2) and 12 patients with a high N/L ratio (2 or more). CD10 and CD35 expressions on neutrophils from the patients with a low N/L ratio were lower than those from the patients with a high N/L ratio. The N/L ratio correlated well with both CD10 and CD35 expression, whereas no correlation was observed between the numbers of neutrophils and the expression of these phenotypes. The respiratory burst of neutrophils from the patients with a high N/L ratio was higher than that of neutrophils from the patients with a low N/L ratio, though there was no correlation in the phagocytic activity between both groups. It was thus suggested that the heterogeneity of neutrophils is, at least partly, related to the prognosis of patients with EGC. Received: 23 October 1997 / Accepted: 15 January 1998     

Galectin-9 prolongs the survival of septic mice by expanding tim-3-expressing natural killer T cells and PDCA-1+ CD11c+ macrophages

Introduction

Galectin-9 ameliorates various inflammatory conditions including autoimmune diseases by regulating T cell and macrophage/dendritic cell (DC) functions. However, the effect of galectin-9 on polymicrobial sepsis has not been assessed.

Methods

We induced polymicrobial sepsis by cecal ligation and puncture (CLP) in mice. The survival rate was compared between galectin-9- and PBS-treated CLP mice. An ELISA was used to compare the levels of various cytokines in the plasma and culture supernatants. Fluorescence-activated cell sorting analysis was further performed to compare the frequencies of subpopulations of spleen cells.

Results

Galectin-9 exhibited a protective effect in polymicrobial sepsis as demonstrated in galetin-9 transgenic mice and therapeutic galectin-9 administration. In contrast, such effect was not observed in nude mice, indicating the involvement of T cells in galectin-9-mediated survival prolongation. Galectin-9 decreased TNFα, IL-6, IL-10 and, high mobility group box 1 (HMGB1) and increased IL-15 and IL-17 plasma and spleen levels. Galectin-9 increased the frequencies of natural killer T (NKT) cells and PDCA-1⁺ CD11c⁺ macrophages (pDC-like macrophages) but did not change the frequency of CD4 or CD8 T cells, γδT cells or conventional DC. As expected, galectin-9 decreased the frequency of Tim-3⁺ CD4 T cells, most likely Th1 and Th17 cells. Intriguingly, many spleen NK1.1⁺ NKT cells and pDC-like macrophages expressed Tim-3. Galectin-9 increased the frequency of Tim-3-expressing NK1.1⁺ NKT cells and pDC-like macrophages. Galectin-9 further increased IL-17⁺ NK1.1⁺ NKT cells.

Conclusion

These data suggest that galectin-9 exerts therapeutic effects on polymicrobial sepsis, possibly by expanding NKT cells and pDC-like macrophages and by modulating the production of early and late proinflammatory cytokines.     

Poly(Ethyleneimine)-Immobilized-Cloth Enzyme Immunoassay for the Detection of Salmonella Lipopolysaccharide

Poly(ethyleneimine) (PEI) was immobilized on non-woven polyester cloth and examined for application on a simple, rapid and economical “cloth enzyme immunoassay (CEIA)” which was developed originally as polymyxin-CEIA for the detection of Salmonella lipopolysaccharide (LPS). PEI-cloth regardless of the PEI molecular weight, but with the amine group contents of 0.1 ∼ 0.35 meq/g immobilized either in a physisorption-like or chemisorption-like manner, adsorbed LPS rapidly, preferentially and effectively. The captured LPS was then able to be detected qualitatively and quantitatively as an antigen by enzyme immunoassay. PEI-CEIA had a detection limit for Salmonella LPS of 10 ng/ml, which was equivalent to 1.6 × 10⁵ cell/ml and was ten times more sensitive than polymyxin-CEIA. It was possible to detect Salmonella LPS in the presence of a 100-fold excess of E. coli LPS. PEI-CEIA was found to be more sensitive and much easier to carry out than polymyxin-CEIA but had the same advantages as polymyxin-CEIA.     

Perioperative Treatment with Infliximab in Patients with Crohn’s Disease and Ulcerative Colitis is Not Associated with an Increased Rate of Postoperative Complications

Purpose  The impact of infliximab (IFX) on postoperative complications in surgical patients with Crohn’s disease (CD) and ulcerative colitis (UC) is unclear. We examined a large patient cohort to clarify whether a relationship exists between IFX and postoperative complications. Methods  A total of 413 consecutive patients—188 (45.5%) with suspected CD, 156 (37.8%) with UC, and 69 (16.7%) with indeterminate colitis—underwent abdominal surgery at the Massachusetts General Hospital between January 1993 and June 2007. One hundred one (24.5%) had received preoperative IFX ≤ 12 weeks before surgery. These patients were compared to those who did not receive IFX with respect to demographics, comorbidities, presence of preoperative infections, steroid use, and nutritional status. We then compared the cumulative rate of complications for each group, which included deaths, anastomotic leak, infection, thrombotic complications, prolonged ileus/small bowel obstruction, cardiac, and hepatorenal complications. Potential risk factors for infectious complications including preexisting infection, pathological diagnosis, and steroid or IFX exposure were further evaluated using logistic regression analysis. Results  Patients were similar with respect to gender (IFX = 40.6% men vs. non-IFX = 51.9%, p = 0.06), age (36.1 years vs.37.8, p = 0.43), Charlson Comorbidity Index (5.3 vs. 5.7, p = 0.25), concomitant steroids (75.3% vs. 76.9%, p = 0.79), preoperative albumin level (3.3 vs. 3.2, p = 0.36), and rate of emergent surgery (3.0% vs. 3.5%, p = 1.00). IFX patients had higher rates of CD (56.4% vs. 41.9%, p = 0.02), concomitant azathioprine/6-mercaptopurine use (34.6% vs. 16.6%, p < 0.0001), and lower rates of intra-abdominal abscess (3.9% vs. 11%, p < 0.05). After surgery, the two groups had similar rates of death (2% vs. 0.3% p = 0.09), anastomotic leak (3.0% vs. 2.9%, p = 0.97), cumulative infections (5.97% vs. 10.1%, p = 1), thrombotic complications (3.6% vs. 3.0%, p = 0.06), prolonged ileus/small bowel obstructions (3.9 vs. 2.8, p = 0.59), cardiac complications (1% vs. 0.6%, p = 0.42), and hepatic or renal complications (1.0 vs. 0.6% p = 0.72). A logistic regression model was then created to assess the impact of IFX, as well as other potential risk factors, on the rates of cumulative postoperative infections. We found that steroids (odds ratio [OR] = 1.2, p = 0.74), IFX (OR 2.5, p = 0.14), preoperative diagnosis of CD (OR = 0.7, p = 0.63) or UC (OR = 0.6, p = 0.48), and preoperative infection (OR = 1.2, p = 0.76) did not affect rates of clinically important postoperative infections. Conclusions  Preoperative IFX was not associated with an increased rate of cumulative postoperative complications. Dr. Sands has received research grants and honoraria for lecturing and consulting from Centocor.