1,720,973 research outputs found
Modulatory Effects of Antibody Replacement Therapy to Innate and Adaptive Immune Cells
Full text linkIntravenous immunoglobulin administered at replacement dosages modulates innate and adaptive immune cells in primary antibody deficiencies (PAD) in a different manner to what observed when high dosages are used or when their effect is analyzed by in vitro experimental conditions. The effects seem to be beneficial on innate cells in that dendritic cells maturate, pro-inflammatory monocytes decrease, and neutrophil function is preserved. The effects are less clear on adaptive immune cells. IVIg induced a transient increase of Treg and a long-term increase of CD4 cells. More complex and less understood is the interplay of IVIg with defective B cells of PAD patients. The paucity of data underlies the need of more studies on patients with PAD before drawing conclusions on the in vivo mechanisms of action of IVIg based on in vitro investigations
Relapsing cellulitis and bacteriemia due to a long lasting (10 years) Campylobacter coli infection in a XLA patient
No full textImmunomodulatory effects of intravenous immunoglobulin - assembling a jigsaw puzzle
No full textIntravenous immunoglobulin (IVIG) is widely used for the treatment of autoimmune and inflammatory disorders because of its immunomodulatory effects. The interaction of IVIG with the immune system has been extensively investigated over the past 30 years but, since IVIG modifies responses of many immune cells, a unifying model is far from reach. Here we survey the in vitro studies on the effects on IVIG on macrophages, B cells, T regulatory cells, dendritic cells and soluble factors, as well as the in vivo studies in murine disease models and the preliminary in vivo findings in humans
Efficacy and safety of long-term treatment with low-dose rituximab for relapsing mixed cryoglobulinemia vasculitis
No full textThis study aims to evaluate the efficacy and safety of repeated treatments with low-dose rituximab for relapsing mixed cryoglobulinemia vasculitis. Thirty-seven patients with mixed cryoglobulinemia vasculitis refractory to standard of care treatment, 34 of which were HCV-positive, were treated with rituximab at the reduced dosage of 250 mg/m2 given twice 1 week apart per cycle. Thirty patients (81%) achieved a clinical response; 5 of them remain in remission, 3 were lost to follow-up or died, and 22 relapsed after a mean of 15.7 months. Eleven relapsers were retreated with one (6 patients), 2 (3 patients), or 3 (2 patients) additional rituximab cycles given at each relapse. Clinical and laboratory efficacy and side effects of long-term treatment were evaluated. Clinical response to retreatment was 91% (10/11) at the first relapse, 80% (4/5) at the second relapse, and 100% (2/2) at the third relapse. The mean (±SD) time to relapse was 17.1 ± 14.1 months in 30 patients who were treated with only one cycle (from first cycle to the first relapse) and 45.7 ± 30.6 months (from first cycle to the last observed relapse) in 11 patients treated with 2 or more cycles (p = 0.0037). Severe adverse reactions occurred in 3 patients, in 2 of whom at the first cycle. Our results suggest that repeated treatment of relapsing mixed cryoglobulinemia with a low-dose rituximab regimen is efficacious, safe, and cost-effective for the long-term management of this disorder
Intravenous immunoglobulin replacement therapy in common variable immunodeficiency induces B cell depletion through differentiation into apoptosis-prone CD21low B cells
No full textntravenous immunoglobulin (IVIG), besides its use as replacement therapy in patients with antibody defi- ciencies, is broadly used as an immunomodulatory agent for the treatment of autoimmune and inflammatory disorders. The mechanisms of action of IVIG include Fc receptor blockade, inhibition of cytokines and growth factors, modulation of macrophages and dendritic cells, enhancement of regulatory T cells, and modulation of B cells through the FccRIIB receptor and CD22. Recent studies suggest that in vitro exposure of human B cells to IVIG determines functional changes reminiscent of anergy and that IVIG treatment of patients with common variable immunodeficiency (CVID) induces in B cells ERK activation, a feature of anergy. Here, we show that IVIG therapy drives the B cells of patients with CVID to down-regulate CD21 expression and to assume the peculiar phenotype of the anergic-like, apoptosis-prone CD21low B cells that are spontaneously expanded in a subset of CVID and in some other immunological disorders. The CD21low B cells newly generated after IVIG infusion undergo spontaneous apoptosis upon in vitro culture. Furthermore, IVIG infusion is rapidly followed by a significant, although discrete, decrease in the number of circulating B cells, but not of T cells or of natural killer cells. These findings suggest that IVIG therapy may constrain antibody responses by inducing B cell depletion through differentiation into CD21low B cells that undergo accelerated apoptosis
Sterile abscesses complicating monoclonal gammopathy of undetermined significance.
No full textA 47-year-old man presented with cough, fever and chest pain. A chest CT scan showed multiple nodules with air cavities in some, and IgGj monoclonal gammopathy of undetermined significance (MGUS) was detected. Blood, sputum and bronchoalveolar lavage cultures were negative for common and acid-fast bacteria or fungi. Antineutrophil cytoplasmic antibodies were negative. Empirical broad-spectrum antibiotic therapy was unsuccessful, while steroid therapy (prednisone 50 mg? d) was followed by rapid clinical and radiological improvement. After steroid withdrawal fever recurred and novel pulmonary nodules developed. An open lung biopsy revealed abscesses with acute and chronic inflammatory areas containing neutrophlis and eosinophils, surrounded by giant epitheloid cells and interstitial fibrosis (Fig. 1A). As steroid therapy was resumed, fever disappeared and nodules regressed. The patient remained well on maintenance steroid therapy for 6 months, but shortly after treatment withdrawal fever relapsed and multiple lung, mesenteric, hepatic and splenic abscesses developed (Fig. 1B). As a predominantly eosinophilic abscess was revealed by liver biopsy, visceral larva migrans was suspected and albendazole was given without success. Based on the absence of microorganisms in the lesions, the failure of antimicrobial therapy, and the efficacy of steroid therapy we diagnosed an ‘aseptic abscesses syndrome,’ a rare condition commonly associated with chronic inflammatory bowel disease or MGU
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