Heterogeneity of B cell involvement in acute nonlymphocytic leukemia

In order to study the pattern of B cell involvement in acute nonlymphocytic leukemia (ANLL), multiple B lymphoid cell lines were established by Epstein-Barr virus transformation of peripheral blood mononuclear cells from two patients with the disease who were heterozygous for the X chromosome-linked glucose-6-phosphate dehydrogenase (G6PD). In one patient, the progenitor cells involved by the leukemia exhibited multipotent differentiative expression, whereas in the other patient the cells showed differentiative expression restricted to the granulocytic pathway. In the patient whose abnormal clone showed multipotent expression, the ratio of B-A G6PD in B lymphoid cell lines was skewed in the direction of type B (the enzyme characteristic of the leukemia clone) and significantly different from the 1:1 ratio expected. It is, therefore, likely that the neoplastic event occurred in a stem cell common to the lymphoid series as well as to the myeloid series. In contrast, evidence for B cell involvement was not detected in the patient whose ANLL progenitor cells exhibited restricted differentiative expression. These findings underscore the heterogeneity of ANLL. Clinically and morphologically similar malignancies in these two patients originated in progenitors with different patterns of stem cell differentiative expression. This difference may reflect differences in cause and pathogenesis.     

CGA-7 and HHF, two monoclonal antibodies that recognize muscle actin and react with adherent cells in human long-term bone marrow cultures

The CGA-7, a monoclonal antibody that reacts with smooth muscle cell actin but not with endothelial cell or fibroblast actin, and HHF, a monoclonal antibody that reacts with smooth muscle, skeletal muscle, and cardiac muscle actin, both recognize microfilaments present within adherent cells from actively hematopoietic human long-term marrow cultures. Macrophages, monocytes, and cultured marrow fibroblasts do not react with either antibody. These data suggest that the anti-actin antibodies may serve as useful markers for in vitro microenvironmental cells and lend support to the hypothesis that stromal cells from long- term marrow cultures are different from marrow fibroblasts and may constitute a unique cell lineage.     

Use of risk stratification to target therapies in patients with recent onset arthritis; design of a prospective randomized multicenter controlled trial

Background  

Early and intensive treatment is important to inducing remission and preventing joint damage in patients with rheumatoid arthritis. While intensive combination therapy (Disease Modifying Anti-rheumatic Drugs and/or biologicals) is the most effective, rheumatologists in daily clinical practice prefer to start with monotherapy methotrexate and bridging corticosteroids. Intensive treatment should be started as soon as the first symptoms manifest, but at this early stage, ACR criteria may not be fulfilled, and there is a danger of over-treatment. We will therefore determine which induction therapy is most effective in the very early stage of persistent arthritis. To overcome over-treatment and under-treatment, the intensity of induction therapy will be based on a prediction model that predicts patients' propensity for persistent arthritis.     

Alcaligenes xylosoxidans conjunctivitis

PURPOSE: To report a case of chronic unilateral conjunctivitis caused by Alcaligenes xylosoxidans. METHODS: A previously healthy 47-year-old woman presented with left eye purulent discharge and irritation beginning 3 months earlier. The patient had previously been treated with bacitracin and olopatadine without improvement. Bacterial staining, culture, and antibiotic sensitivities were performed from a conjunctival swab. RESULTS: The cultures revealed heavy growth of A. xylosoxidans. The organism was resistant to aminoglycosides, fluoroquinolones, and cephalosporins. The patient was started on polytrim, but an allergic reaction forced the use of topical Timentin 2%. After 14 days of treatment, the infection completely resolved. CONCLUSIONS: To our knowledge, this is the first case report of an external ocular infection caused by A. xylosoxidans in a host without predisposing risk factors and the first case report of isolated conjunctivitis caused by A. xylosoxidans. A. xylosoxidans should be considered a rare but potential pathogen capable of producing chronic conjunctivitis in an otherwise healthy host.     

Addition of Plasmapheresis Decreases the Incidence of Acute Antibody-Mediated Rejection in Sensitized Patients with Strong Donor-Specific Antibodies

Background and objectives: The objective of this study was to investigate the effects of desensitization protocols using intravenous Ig with or without plasmapheresis in patients with donor-specific anti-HLA antibodies on prevention of antibody-mediated rejection and downregulation of donor-specific antibodies.Design, setting, participants, & measurements: Thirty-five complement-dependent cytotoxicity T cell cross-match–negative but complement-dependent cytotoxicity B cell and/or flow cytometry cross-match–positive kidney transplant recipients were treated with high-dosage intravenous Ig plus Thymoglobulin induction treatment. Donor-specific antibody strength was stratified as strong, medium, or weak by Luminex flow beads. Group 1 patients had weak/moderate and group 2 strong donor-specific antibodiesResults: Whereas no group 1 patients had acute rejection, 66% of group 2 had acute rejection (44% antibody-mediated rejection, 22% cellular rejection). The protocol was then changed to the addition of peritransplantation plasmapheresis to patients with strong donor-specific antibodies (group 3). This change resulted in a dramatic decrease in the acute rejection rate to 7%. During a median 18 mo of follow-up, patient survival was 100, 100, and 93% and graft survival was 100, 78, and 86% in groups 1, 2, and 3, respectively. During follow-up, 17 (52%) patients lost donor-specific antibodies completely, and 10 (30%) lost some of donor-specific antibodies and/or decreased the strength of existing donor-specific antibodies.Conclusions: These results indicated that in patients with strong donor-specific antibodies, the addition of plasmapheresis to high-dosage intravenous Ig decreases the incidence of acute rejection. The majority of the patients, whether they received intravenous Ig alone or with plasmapheresis, lost their donor-specific antibodies during follow-up.Donor-specific anti-HLA antibodies (DSA) in patients who are sensitized through pregnancy, previous blood transfusions, or organ transplantation is an important obstacle in kidney transplantation. Sensitized patients wait longer on the deceased-donor transplantation list, may not receive a transplant, and may have greater morbidity and mortality. Some sensitized patients may have living donor candidates, but transplantation cannot be performed because of cross-match positivity. Recent desensitization protocols using the combination of plasmapheresis (PP) or immunoadsorption to remove DSA and/or intravenous Ig (IVIG) and rituximab to downregulate antibody-mediated immune responses have made kidney transplantation feasible by abrogating complement-dependent cytotoxicity (CDC) T cell cross-match positivity. In previous studies, two protocols were examined: High-dosage IVIG (2.0 g/kg) (1–3) and PP with low-dosage IVIG (100 mg/kg after each PP session) (4–8); however, acute antibody-mediated rejection (AMR) continued to be an important barrier and was still observed in at least 30 to 40% of the recipients included in these desensitization protocols, even when rituximab was added to the protocol.Whereas CDC T cell cross-match positivity is an absolute contraindication to kidney transplantation, the clinical significance of CDC B cell or flow cytometry (FC) T and/or B cell cross-match positivity are less clear. Most studies have demonstrated that CDC T cell cross-match–negative but CDC B or FC T/B cell cross-match–positive patients with DSA are at higher risk for developing acute cellular, antibody-mediated, and chronic rejection and graft loss (9,10). The role of desensitization protocols for these patients has not been studied in a large cohort. We previously reported our initial experience using low-dosage IVIG (300 mg/kg) and Thymoglobulin induction treatment in 15 patients (11,12). Because of early AMR in three patients, the IVIG dosage was increased to a total of 2.0 mg/kg in subsequent patients. Now, we present our experience in CDC T cell–negative but CDC B cell or FC T and/or B cell cross-match–positive kidney transplant recipients with DSA, who were stratified according to mean fluorescence indices of Luminex flow beads. The results showed that patients with strong DSA were at much higher risk for developing acute AMR early after transplantation, and the addition of peritransplantation PP to high-dosage IVIG and Thymoglobulin treatment significantly decreased the incidence of AMR. The majority of the patients, whether they received IVIG alone or with PP, lost DSA during follow-up.