Diagnostic and prognostic roles of soluble CD22 in patients with Gram-negative bacterial sepsis.

BACKGROUND: Soluble CD22 (sCD22) is a fragment of CD22, a B cell-specific membrane protein that negatively regulates B-cell receptor signaling. To date, sCD22 has only been regarded as a tumor marker of B-cell malignancies. Its expression in infectious diseases has not yet been assessed. METHODS: Serum concentrations of sCD22, procalcitonin (PCT) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assays in patients with intra-abdominal Gram-negative bacterial infection. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic accuracy of these biomarkers in this type of infection. The correlations between biomarkers and the Acute Physiology and Chronic Health Evaluation (APACHE) II scores were also analyzed. RESULTS: Concentrations of sCD22 were significantly elevated in patients with sepsis and the elevation is correlated with the severity of sepsis. sCD22 was also slightly elevated in patients with non-infected systemic inflammatory response syndrome or local infection. The diagnostic accuracy of sCD22 for sepsis was equivalent to that of PCT or IL-6. In addition, the correlation of sCD22 with APACHE II scores was stronger than that of PCT or IL-6. CONCLUSIONS: Serum sCD22 is a novel inflammatory mediator released during infection. This soluble biomarker plays a potential role in the diagnosis of Gram-negative bacterial sepsis, with a diagnostic accuracy as efficient as that of PCT or IL-6. Furthermore, sCD22 is more valuable to predict the outcomes in patients with sepsis than PCT or IL-6. The present study suggested that sCD22 might be potentially useful in supplementing current criteria for sepsis.

Pharmacokinetic and pharmacodynamic comparability study of moxetumomab pasudotox, an immunotoxin targeting CD22, in cynomolgus monkeys.

Moxetumomab pasudotox is an immunotoxin currently being investigated in patients for the treatment of CD22-expressing B-cell malignancies. A single-cycle pharmacokinetic (PK)-pharmacodynamic (PD) study was conducted in cynomolgus monkeys for PK comparability assessment and population PK-PD modeling after major manufacturing process and site changes. Primates were randomized by body weight and baseline CD22 lymphocyte counts to receive intravenous administrations of 1 mg/kg moxetumomab pasudotox (n = 12/group) on Days 1, 3, and 5. PK and B-lymphocyte count data were modeled using a population approach. The 90% confidence intervals of the geometric mean ratios of PK exposure were within the 80%-125% range. The B lymphocytes were depleted to a similar extent, and the immunogenicity incidences were similar across the two groups. The B-cell depletion was described by a novel lifespan model in which moxetumomab pasudotox induced random destruction of B cells in each aging compartment. The endogenous de novo influx from bone marrow was subject to a negative feedback mechanism. The estimated B cell apparent lifespan was 51 days. Covariate analysis confirmed that the manufacturing change had no impact on PK or PD of moxetumomab pasudotox. Results from this study supported continued clinical investigation of moxetumomab pasudotox using the new material.

Haptoglobin polymorphism: a key factor in the proatherogenic role of B cells?

B cells play a role in atherosclerosis. B lymphocytes may reduce the progression of vascular disease. Antibody production against modified auto-antigens is an element in the atheroprotective involvement of B lymphocytes. Paradoxical evidence is emerging from animal studies that suggest a proatherogenic B-cell behaviour independently of autoantibody production. One aspect that has received limited consideration is the role of genetic susceptibility modulated by extracellular matrix proteins. Haptoglobin is a polymorphic glycoprotein that binds to CD22 on B lymphocytes. Hp phenotypes show an important molecular heterogeneity. Hp 2-2 has been linked to an increased susceptibility for atherosclerosis. Haptoglobin and its polymorphism play a role in B-cell migration and function. Hp phenotypes may influence B-T cell dialogue and T cell activation. Haptoglobin is involved in the interplay of lymphocytes, neutrophils, and monocytes. Haptoglobin binds to the CD11b/CD18 receptor and to mast cells. HDL particles can become pro-inflammatory through interactions of Hp-Hb complexes with apolipoprotein A1. Haptoglobin is a chemoattractant to pre-B lymphocytes and monocytes. Beyond the conventional view of haptoglobin as a marker of hemolysis, several findings point towards an immunomodulatory effect of haptoglobin in B-cell mediated progression of atherosclerosis. The balance between proatherogenic and protective immunological properties of the different Hp phenotypes determines if lesions progress or regress. Clinical studies indicate a strong association between the Hp 2-2 phenotype and a more frequent onset of diabetic complications and cardiovascular disease. Findings in animal models (where no haptoglobin polymorphism is present) cannot always be extrapolated to humans.

CD22 expression on blastic plasmacytoid dendritic cell neoplasms and reactivity of anti-CD22 antibodies to peripheral blood dendritic cells.

We identified CD22 expression on a blastic plasmacytoid dendritic cell (pDC) neoplasm presenting as a leukemia in a child. CD22 expression, as determined by the antibody s-HCL-1, was also noted on the neoplastic cells from three additional patients with blastic pDC tumors identified at our institution. Subsequently we determined that peripheral blood pDCs react with the s-HCL-1 antibody demonstrating that normal pDCs express CD22. Evaluation of five additional anti-CD22 antibodies indicated that staining of pDCs with these reagents was poor except for s-HCL-1. Therefore, the detection of CD22 on pDCs is best demonstrated with the use of this specific antibody clone. All anti-CD22 antibodies stained conventional DCs. We also evaluated the reactivity of the anti-CD22 antibodies with basophils and noted that the pattern of staining was similar to that seen with pDCs. The studies demonstrate that normal DCs and pDC neoplasms express CD22, and highlight clone specific differences in anti-CD22 antibody reactivity patterns on pDCs and basophils.

Altered CD19/CD22 balance in Egyptian children and adolescents with systemic lupus erythematosus.

B cells from systemic lupus erythematosus (SLE) patients display signalling defects that may underlie disease pathogenesis activity.CD19 and CD22 play a major role as regulators of B-cell response. The aim of this study was to clarify the relationship between B cell surface markers namely CD19, CD20 and CD22 expression and clinical and laboratory indices of SLE activity. The study included 33 SLE patients and 20 healthy children and adolescents as controls. Flowcytometric assay of dual markers, CD19/CD20, and CD20/CD22 was done. SLE disease activity was assessed by SLEDAI score. CD22% was significantly higher while CD20% was significantly lower in the study compared to the control group. No significant difference was observed in both groups with respect to CD19% or CD19/CD22% ratio. The level of CD22 expression was significantly lower in high and very high active cases than in mild and moderate cases and negatively correlated with SLDEAI score and ESR. Results obtained showed that, B cell surface receptors CD20 and CD22 are significantly affected in patients with SLE, pointing to their possible involvement in the aetiopathogenesis of the disease and in the regulatory mechanisms in response to the immune disturbance.

Soluble CD22 as a tumor marker for hairy cell leukemia.

CD22 is an important immunotherapeutic target on B-cell malignancies, particularly hairy cell leukemia (HCL), but its soluble extracellular domain, sCD22, has not yet been reported in the blood. By immunoaffinity and enzyme-linked immunosorbent assay techniques using anti-CD22 monoclonal antibodies, we identified the 100-kDa extracellular domain of CD22 and an 80-kDa processed form in serum of patients with HCL. The median sCD22 level measured by enzyme-linked immunosorbent assay was 18 ng/mL for 93 patients with HCL. sCD22 levels varied from 2.1 to 163 ng/mL and were higher (P < .001) than 23 normal donors (median, 0.6 ng/mL). More than 95% of normal donors had sCD22 levels less than 1.9 ng/mL. sCD22 levels were proportional to concentrations of circulating HCL cells (P = .002), and HCL spleen size (P < .001). sCD22 levels normalized with complete but not partial response to treatment. sCD22 levels up to 300 ng/mL had less than a 2-fold effect on the cytotoxicity of the anti-CD22 recombinant immunotoxin BL22. sCD22 levels may be useful to follow in patients with HCL and may be more specific than sCD25 in patients with CD22(+)/CD25(-) disease. Trials are listed on www.cancer.gov as NCT00002765, NCT00021983, NCT00074048, NCT00085085, NCT00337311, and NCT00462189.

Differential effects of epratuzumab on peripheral blood B cells of patients with systemic lupus erythematosus versus normal controls.

OBJECTIVE: B lymphocytes have been implicated in the pathogenesis of lupus and other autoimmune diseases, resulting in the introduction of B cell-directed therapies. Epratuzumab, a humanised anti-CD22 monoclonal antibody, is currently in clinical trials, although its effects on patients' B cells are not completely understood. METHODS: This study analysed the in vivo effect of epratuzumab on peripheral B cell subsets in 12 patients with systemic lupus erythematosus, and also addressed the in vitro effects of the drug by analysing anti-immunoglobulin-induced proliferation of isolated B cells obtained from the peripheral blood of 11 additional patients with lupus and seven normal subjects. RESULTS: Upon treatment, a pronounced reduction of CD27(-) B cells and CD22 surface expression on CD27(-) B cells was observed, suggesting that these cells, which mainly comprise naïve and transitional B cells, are preferentially targeted by epratuzumab in vivo. The results of in vitro studies indicate additional regulatory effects of the drug by reducing the enhanced activation and proliferation of anti-immunoglobulin-stimulated lupus B cells after co-incubation with CD40L or CpG. Epratuzumab inhibited the proliferation of B cells from patients with systemic lupus erythematosus but not normal B cells under all culture conditions. CONCLUSIONS: Epratuzumab preferentially modulates the exaggerated activation and proliferation of B cells from patients with lupus in contrast to normal subjects, thus suggesting that epratuzumab might offer a new therapeutic option for patients with systemic lupus erythematosus, as enhanced B cell activation is a hallmark of this disease.

[Cytology and immunophenotyping of acute promyelocytary leukaemia]. / Cytologie et immunophénotypage des leucémies aiguës promyélocytaires.

Acute promyelocytic leukaemia (AML3) is characterized by particular clinical and biological features. We report the cytology and the immunophenotype of 14 AML3 from which 3 were AML3v. A double negativity of HLA-DR and CD34 is found in 12 cases and aberrant expression of CD2 in 2AML3v. Aberrant expression of CD56 and CD22 was shown in, respectively, one case, CD15, CD65 and CD117 expressions were variable. Cytological diagnosis is often evident, although in some cases, it is not typical and immunophenotype will contribute to the diagnosis.