Immunological abnormalities in patients with early-onset ataxia with ocular motor apraxia and hypoalbuminemia.

Early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH) is a neurodegenerative disorder caused by mutation in the aprataxin (APTX)-coding gene APTX, which is involved in DNA single-strand break repair (SSBR). The neurological abnormalities associated with EAOH are similar to those observed in patients with ataxia-telangiectasia. However, the immunological abnormalities in patients with EAOH have not been described. In this study, we report that EAOH patients have immunological abnormalities, including lymphopenia; decreased levels of CD4+ T-cells, CD8+ T-cells, and B-cells; hypogammaglobulinemia; low T-cell recombination excision circles and kappa-deleting element recombination circles; and oligoclonality of T-cell receptor ß-chain variable repertoire. These immunological abnormalities vary among the EAOH patients. Additionally, mild radiosensitivity in the lymphocytes obtained from the patients with EAOH was demonstrated. These findings suggested that the immunological abnormalities and mild radiosensitivity evident in patients with EAOH could be probably caused by the DNA repair defects.

Effects of Albumin Treatment on Systemic and Portal Hemodynamics and Systemic Inflammation in Patients With Decompensated Cirrhosis.

BACKGROUND & AIMS: We investigated the effect of albumin treatment (20% solution) on hypoalbuminemia, cardiocirculatory dysfunction, portal hypertension, and systemic inflammation in patients with decompensated cirrhosis with and without bacterial infections. METHODS: We performed a prospective study to assess the effects of long-term (12 weeks) treatment with low doses (1 g/kg body weight every 2 weeks) and high doses (1.5 g/kg every week) of albumin on serum albumin, plasma renin, cardiocirculatory function, portal pressure, and plasma levels of cytokines, collecting data from 18 patients without bacterial infections (the Pilot-PRECIOSA study). We also assessed the effect of short-term (1 week) treatment with antibiotics alone vs the combination of albumin plus antibiotics (1.5 g/kg on day 1 and 1 g/kg on day 3) on plasma levels of cytokines in biobanked samples from 78 patients with bacterial infections included in a randomized controlled trial (INFECIR-2 study). RESULTS: Circulatory dysfunction and systemic inflammation were extremely unstable in many patients included in the Pilot-PRECIOSA study; these patients had intense and reversible peaks in plasma levels of renin and interleukin 6. Long-term high-dose albumin, but not low-dose albumin, was associated with normalization of serum level of albumin, improved stability of the circulation and left ventricular function, and reduced plasma levels of cytokines (interleukin 6, granulocyte colony-stimulating factor, interleukin 1 receptor antagonist, and vascular endothelial growth factor) without significant changes in portal pressure. The immune-modulatory effects of albumin observed in the Pilot-PRECIOSA study were confirmed in the INFECIR-2 study. In this study, patients given albumin had significant reductions in plasma levels of cytokines. CONCLUSIONS: In an analysis of data from 2 trials (Pilot-PRECIOSA study and INFECIR-2 study), we found that albumin treatment reduced systemic inflammation and cardiocirculatory dysfunction in patients with decompensated cirrhosis. These effects might be responsible for the beneficial effects of albumin therapy on outcomes of patients with decompensated cirrhosis. ClinicalTrials.gov, Numbers: NCT00968695 and NCT03451292.

Inflammatory factors for hypoalbuminemia in Japanese peritoneal dialysis patients.

AIM: Hypoalbuminaemia is a common complication of peritoneal dialysis (PD), and the leakage of albumin through peritoneal membrane may be a principal reason for hypoalbuminaemia. However, the relationship between peritoneal inflammation, peritoneal transport properties and hypoalbuminaemia has not been fully elucidated. METHODS: A cross-sectional study was performed on 76 Japanese PD patients who had been using a low-glucose PD solution and icodextrin. Systemic inflammatory markers of C-reactive protein (CRP) and serum interleukin-6 (IL-6), peritoneal effluent markers of dialysate IL-6 and CA125, the dialysate-to-plasma ratio of creatinine (D/Pcr) and the dialysate protein concentration were measured and examined for their relationship with hypoalbuminaemia. RESULTS: There was a significant positive correlation between serum IL-6 and dialysate IL-6, mean dialysate IL-6 being significantly higher than mean serum IL-6, suggesting that intraperitoneal inflammation was a principal origin of systemic inflammation. Both serum and dialysate IL-6 were significantly correlated with serum albumin (r= -0.25, P<0.05 and r=-0.32, P<0.01, respectively). Dialysate IL-6 was significantly correlated with D/Pcr and the dialysate protein concentration, and there was a significantly positive association between D/Pcr and the dialysate protein concentration. Dialysate CA125, which is argued to be a marker of mesothelial cell mass in this study, was positively correlated with D/Pcr and the dialysate protein concentration. The dialysate protein, dialysate IL-6 and dialysate CA125 all increased according to the peritoneal transport rate defined by D/Pcr. A multiple-regression analysis showed that serum albumin was independently associated with the age, D/Pcr and serum IL-6. CONCLUSION: Hypoalbuminaemia was attributable to both the increased peritoneal permeability and systemic inflammation, and intraperitoneal inflammation might contribute to developing these complications.

Cronkhite-Canada syndrome: report of a rare case and review of the literature.

Cronkhite-Canada syndrome is rarely encountered in clinical practice. Notably, most patients with Cronkhite-Canada syndrome exhibit hypoalbuminemia. Because the cause of Cronkhite-Canada syndrome is unknown, no specific treatment method has been established. Here, we describe a 59-year-old woman with Cronkhite-Canada syndrome in whom clinical manifestations were considerably relieved after treatment with prednisone.

Serum antibodies against human albumin in critically ill and healthy dogs.

OBJECTIVE: To characterize the magnitude and duration of the antibody response against human albumin (HA) in critically ill and healthy dogs. DESIGN: Cohort and cross-sectional study. ANIMALS: Fourteen critically ill dogs that received 25% HA as part of their treatment protocol, 2 healthy dogs with no known previous exposure to HA that received 2 infusions of 25% HA (positive control dogs), and 47 healthy dogs and 21 critically ill dogs with no known exposure to HA (negative control dogs). PROCEDURES: An ELISA to detect IgG against HA was developed. Serum samples were obtained from the critically ill dogs prior to infusion of HA, at the time of hospital discharge, and 4 to 6 weeks and 6 months after HA administration. Serum samples were obtained at 2- to 4-week intervals from both positive control dogs for 101 weeks. A single serum sample was obtained from each of the negative control dogs. RESULTS: All 14 critically ill dogs developed serum IgG against HA. Peak antibody response was detected 4 to 6 weeks after HA administration. In both positive control dogs, IgG against HA was detected 10 days after HA administration and continued past 97 weeks. The peak antibody response was detected at 3 weeks in 1 dog and at 9 weeks in the other. Five of the 68 (7%) negative control dogs had a positive antibody response. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that dogs developed a pronounced IgG response following exposure to HA and that some dogs with no history of HA administration were positive for anti-HA IgG.

Rituximab in severe lupus nephritis: early B-cell depletion affects long-term renal outcome.

BACKGROUND AND OBJECTIVES: Standard treatment for lupus nephritis, including corticosteroids and cyclophosphamide, is efficient but is still associated with refractory or relapsing disease, or severe deleterious effects. Rituximab, a monoclonal chimeric anti-B cell antibody, is increasingly used in patients with lupus nephritis, but reported series were small and had a short follow-up. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The authors analyzed clinical and histologic data of 20 patients who were treated with rituximab for lupus nephritis and followed up for at least 12 mo. RESULTS: Nineteen women and one man received rituximab as induction treatment for an active class IV (15 cases) or class V (5 cases) lupus nephritis. Rituximab was given for lupus nephritis refractory to standard treatment (12 cases), for relapsing disease (6 cases), or as first-line treatment (2 cases). Three patients received cyclophosphamide concomitantly with rituximab. Ten received new injections of rituximab as maintenance therapy. Side effects included mainly five infections and four moderate neutropenias. After a median follow-up of 22 mo, complete or partial renal remission was obtained in 12 patients (60%). Lupus nephritis relapsed in one patient, who responded to a new course of rituximab. The achievement of B cell depletion 1 mo after rituximab, which negatively correlated with black ethnicity and hypoalbuminemia, was strongly associated with renal response. Rapidly progressive glomerulonephritis did not respond to rituximab. CONCLUSION: Rituximab is an interesting therapeutic option in relapsing or refractory lupus nephritis when early B cell depletion is obtained.