scholarly journals Cell surface-expressed Ro52/IgG/HLA-DR complex is targeted by autoantibodies in patients with inflammatory myopathies

2022 ◽  
Vol 126 ◽  
pp. 102774
Author(s):  
Noriko Arase ◽  
Hideaki Tsuji ◽  
Hyota Takamatsu ◽  
Hui Jin ◽  
Hachiro Konaka ◽  
...  
1997 ◽  
Vol 25 (2) ◽  
pp. 259S-259S ◽  
Author(s):  
Kathy Triantafilou ◽  
Keith M. Wilson ◽  
Nelson Fernandez

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Serkan Yazıcı ◽  
Emel Bülbül Başkan ◽  
Ferah Budak ◽  
Barbaros Oral ◽  
Şaduman Balaban Adim ◽  
...  

We retrospectively analyzed the clinicopathological correlation and prognostic value of cell surface antigens expressed by peripheral blood mononuclear cells in patients with mycosis fungoides (MF). 121 consecutive MF patients were included in this study. All patients had peripheral blood flow cytometry as part of their first visit. TNMB and histopathological staging of the cases were retrospectively performed in accordance with International Society for Cutaneous Lymphomas/European Organization of Research and Treatment of Cancer (ISCL/EORTC) criteria at the time of flow cytometry sampling. To determine prognostic value of cell surface antigens, cases were divided into two groups as stable and progressive disease. 17 flow cytometric analyses of 17 parapsoriasis (PP) and 11 analyses of 11 benign erythrodermic patients were included as control groups. Fluorescent labeled monoclonal antibodies were used to detect cell surface antigens: T cells (CD3+, CD4+, CD8+, TCRαβ+, TCRγδ+, CD7+, CD4+CD7+, CD4+CD7−, and CD71+), B cells (HLA-DR+, CD19+, and HLA-DR+CD19+), NKT cells (CD3+CD16+CD56+), and NK cells (CD3−CD16+CD56+). The mean value of all cell surface antigens was not statistically significant between parapsoriasis and MF groups. Along with an increase in cases of MF stage statistically significant difference was found between the mean values of cell surface antigens. Flow cytometric analysis of peripheral blood cell surface antigens in patients with mycosis fungoides may contribute to predicting disease stage and progression.


1991 ◽  
Vol 2 (3) ◽  
pp. 227
Author(s):  
Shuhei Imayama ◽  
Yutaka Yashima ◽  
Minao Furumura ◽  
Yoshiaki Hori

1982 ◽  
Vol 156 (1) ◽  
pp. 104-111 ◽  
Author(s):  
JP Johnson ◽  
T Meo ◽  
G Reithmuller ◽  
DJ Schendel ◽  
R Wank

A murine monoclonal antibody directed against a human B cell surface antigen with the characteristics of HLA-DR is described. The antigen detected is tightly linked to HLA and is correlated with the alloantigen HLA-Dw/DR3. Reactivity with a fraction of Dw/DRw6 cells is also observed. The determinant recognized by this antibody has been shown to be present on the smaller molecular weight β subunit of the HLA-DR antigen.


Blood ◽  
1987 ◽  
Vol 69 (3) ◽  
pp. 957-960 ◽  
Author(s):  
T Koike ◽  
S Aoki ◽  
S Maruyama ◽  
M Narita ◽  
T Ishizuka ◽  
...  

Abstract Surface phenotypic characterization of megakaryoblasts, identified by platelet peroxidase activity, was investigated in four patients who showed increased proliferation of megakaryoblasts: one patient with typical features of acute leukemia, one presenting with acute myelofibrosis, and two with Down's syndrome in whom blasts disappeared spontaneously (transient abnormal myelopoiesis, TAM). MY10 and/or MY9 antigens were expressed on the surface of some megakaryoblasts, but MY7, and MY4, antigens specific to granulocytic or monocytic cells, were not. Some megakaryoblasts were positive for only anti-HLA-DR antibodies. It was speculated that, during the differentiation of the megakaryocytic lineage, MY9 antigen appears transiently on the surface of megakaryoblasts that have lost HLA-DR antigens and have gained the glycoprotein IIb/IIIa antigen. This study also demonstrated that the proliferating blasts in some patients with TAM were mainly megakaryoblasts and suggested that the target cells in TAM are CFU-GEMM.


Blood ◽  
1994 ◽  
Vol 83 (8) ◽  
pp. 2103-2114 ◽  
Author(s):  
SJ Thoma ◽  
CP Lamping ◽  
BL Ziegler

Abstract A strategy to phenotype rare populations of hematopoietic cells expressing the cell-surface marker CD34 was studied. The antigenic phenotype of umbilical core blood (CB) CD34+ cells was investigated using flow cytometry and compared with the mRNA-phenotype determined by cDNA-polymerase chain reaction (cDNA-PCR) analysis. The cDNA-PCR method allowed an mRNA evaluation of small numbers of cells. Monoclonal antibodies and oligonucleotide primers that recognize myeloid, lymphoid, erythroid and platelet/megakaryocytic cell membrane antigens or corresponding mRNA transcripts were used. Evaluation by flow cytometry showed that the vast majority of CD34+ CB cells coexpressed CD38, CD18, HLA-DR, and CD33. Rare subpopulations of CD34+CD38-, CD34+CD18-, CD34+HLA-DR-, and CD34+CD33- were also identified. A large proportion of CD34+ CB cells expressed CD13, CD45R, and to a lesser extent CD71. The CD36, CD51, and CD61 antigens were identified on a small number of CD34+ cells. The three-color flow cytometry analysis showed that CD34+ cells stained with antibodies to CD61 and CD36 or CD51 can be divided into subsets that may represent progenitor cells committed to the erythroid and/or megakaryocytic lineage. A variety of other lineage-specific cell-surface antigens including pre-T-cell marker CD7 and markers of early B cells, ie, CD10 and CD19, were not coexpressed with CD34+. Using the cDNA-PCR it was seen that the mRNA phenotype of a small number of sorted CD34+ cells (purity > 98%) was negative for the markers CD2, CD14, CD16, CD20, CD21, CD22, CD41b, and glycophorin A that are expressed on differentiated cells but positive for CD34, CD7, CD19, CD36, and CD61. The results suggest that circulating CD34+CD7+ and CD34+CD19+ CB cells cannot be distinguished by flow cytometry but can be detected by cDNA-PCR. This indicates that CB either contains very low numbers of these progenitors or that the antigen density of CD7 and CD19 on CD34+ cells is below the detection limit of the flow cytometer. In contrast to flow cytometry, cDNA-PCR allows the phenotypic analysis of cells even if their number is small. Thus, the cDNA-PCR method can be useful in linking phenotype analyses, ie, markers of differentiation, to studies on gene expression within rare populations of hematopoietic stem cells.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2345-2345
Author(s):  
Pau Montesinos ◽  
Concepcion Rivas ◽  
Consuelo Rayon ◽  
Edo Vellenga ◽  
Javier de la Serna ◽  
...  

Abstract Introduction: The prognostic significance of the expression pattern of certain cell surface markers in APL is controversial. Objectives: Analyse the impact of the expression of certain cell surface markers on complete remission rate (CR), overall survival (OS) and relapse free survival (RFS) in patients with APL included in multicenter trials PETHEMA LPA96 y LPA99. Material and methods: Between 1996 and 2005, 734 patients were included in these 2 consecutive trials. Induction therapy consisted of ATRA and idarubicin, followed by three consolidation courses of anthracycline monochemotherapy with or without ATRA and followed by maintenance. Bone marrow immunophenotype analysis was performed at local or reference laboratories. Positivity was defined as more than 20% blasts expressing a specific antigen for the following antigens: CD34 (527 patients), CD33 (521), CD15 (520), CD13 (513), HLA-DR (495), CD2 (443), CD19 (433), CD7 (403), CD117 (395), CD56 (392), y CD11b (335). We performed univariate analysis to establish the impact of antigen positivity on CR rate, OS and RFS. Significant values were included in the multivariate analysis. Results: A total of 664 patients (90%) achieved CR. The following variables were associated with decreased CR rate: WBC > 10x109/L, serum level creatinine > 1.4 mg/dl, age > 60 years, ECOG > 1, M3v and male gender. None of the cell surface antigens were significantly associated with CR rate. WBC, creatinine, age and gender were found to be independent prognostic factors for CR. Median follow up was 55 months. OS at 8 years was inferior in those patients with WBC > 10x109/L (67% vs 85%, p < 0.01), M3v (70% vs 83%, p < 0.01), age > 60 (56% vs 86%, p < 0.01), male gender (78% vs 83%, p=0.03), LPA96 trial (74% vs 84%, p=0.01) and CD2+ (76% vs 84%, p=0.04). Age, WBC and gender were independent factors for OS. RFS was inferior in those patients with WBC > 10x109/L (69% vs 93%, p < 0.01), high vs intermediate vs low risk (69% vs 91% vs 95%, p < 0.01), M3v (76% vs 88%, p < 0.01), BCR2 vs BCR3 vs BCR1 transcript (71% vs 81% vs 89%, p < 0.01), male gender (83% vs 90%, p=0.03), LPA96 trial (82% vs 87%, p=0.02) and CD2+ (75% vs 91%, p < 0.01). The risk of relapse category was the only independent factor for RFS. CD2+ APL (115/443 patients) was significantly associated with WBC > 10x109/L, M3v, BCR3, CD34+, CD56+, CD7+, and HLA-DR negative. Conclusion: Of all the cell surface antigens analysed, only expression of CD2 was associated with an lower OS and RFS, due to its association with WBC > 10x109/L. In patients taking part in PETHEMA trials, immunophenotype analysis at presentation does not give additional prognostic impact from the previously established risk factors.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3078-3078
Author(s):  
Diane L Rossi ◽  
Edmund A Rossi ◽  
David M Goldenberg ◽  
Chien-Hsing Chang

Abstract Background Various formats of bispecific antibodies (bsAbs) to redirect effector T cells for the targeted killing of tumor cells have shown considerable promise both pre-clinically and clinically. The scFv-based constructs, including BiTE and DART, which bind monovalently to CD3 on T cells and to the target antigen on tumor cells, exhibit fast blood clearance and neurological toxicity due to their small size (∼55 kDa). Herein, we describe the generation of novel T-cell redirecting trivalent bsAbs comprising an anti-CD3 scFv covalently conjugated to a stabilized F(ab)2. The design was initially characterized with a prototype construct designated (19)-3s, which specifically targets CD19 on B cells. A panel of trivalent bsAbs was evaluated for their potential use in targeted T-cell immunotherapy of various B-cell malignancies. Potential advantages of this design include bivalent binding to tumor cells, a larger size (∼130 kDa) to preclude rapid renal clearance and penetration of the blood-brain barrier, and potent T-cell mediated cytotoxicity. Methods The DOCK-AND-LOCKTM (DNLTM) method was used to generate a panel of B-cell targeting bsAbs, (19)-3s, (20)-3s, (22)-3s, and (C2)-3s, which target CD19, CD20, CD22, and HLA-DR, respectively. This was achieved by combining a stabilized anti-X F(ab)2 with an anti-CD3-scFv, resulting in a homogeneous covalent structure of the designed composition, as shown by LC-MS, SE-HPLC, ELISA, SDS-PAGE, and immunoblot analyses. Each construct can mediate the formation of immunological synapses between T cells and malignant B cells, resulting in T-cell activation. At an E:T ratio of 10:1, using isolated T cells as effector cells, the bsAbs induced potent T-cell-mediated cytotoxicity in various B-cell malignancies, including Burkitt lymphomas (Daudi, Ramos, Namalwa), mantle cell lymphoma (Jeko-1), and acute lymphoblastic leukemia (Nalm-6). A non-tumor binding control, (14)-3s, induced only moderate T-cell killing at >10 nM. The nature of the antigen/epitope, particularly its size and proximity to the cell surface, appears to be more important than antigen density for T-cell retargeting potency (Table 1). It is likely that (20)-3s is consistently more potent than (19)-3s and (C2)-3s, even when the expression of CD19 or HLA-DR is considerably higher than CD20, as seen with Namalwa and Jeko-1, respectively. This is likely because the CD20 epitope comprises a small extracellular loop having close proximity to the cell surface. When compared directly using Daudi, (22)-3s was the least potent. Compared to CD19 and CD20, CD22 is expressed at the lowest density, is a rapidly internalizing antigen, and its epitope is further away from the cell surface; each of these factors may contribute to its reduced potency. Finally, sensitivity to T-cell retargeted killing is cell-line-dependent, as observed using (19)-3s, where Raji (IC50 >3 nM) is largely unresponsive yet Ramos (IC50 = 2 pM) is highly sensitive, even though the former expresses higher CD19 antigen density. Conclusions (19)-3s, (20)-3s, (22)-3s, and (C2)-3s can bind T cells and target B cells simultaneously and induce T-cell-mediated killing in vitro. The modular nature of the DNL method allowed the rapid production of several related conjugates for redirected T-cell killing of various B-cell malignancies, without the need for additional recombinant engineering and protein production. The close proximity of the CD20 extracellular epitope to the cell surface results in the highest potency for (20)-3s, which is an attractive candidate bsAb for use in this platform. We are currently evaluating the in vivo activity of these constructs to determine if this novel bsAb format offers additional advantages. Disclosures: Rossi: Immunomedics, Inc.: Employment. Rossi:Immunomedics, Inc.: Employment. Goldenberg:Immunomedics: Employment, stock options, stock options Patents & Royalties. Chang:Immunomedics, Inc: Employment, Stock option Other; IBC Pharmaceuticals, Inc.: Employment, Stock option, Stock option Other.


1996 ◽  
Vol 5 (5) ◽  
pp. 362-369
Author(s):  
W. A. T. Slieker ◽  
P. Th. W. van Hal ◽  
J. M. Wijkhuijs ◽  
J. P. M. Hopstaken-Broos ◽  
J. A. Noordhoek ◽  
...  

At present, inhaled glucocorticoids are widely accepted as the therapy of choice in chronic asthma. Treatment with inhaled glucocorticoids significantly suppresses local airway inflammation in asthmatics, but may also have systemic effects, e.g. a reduction of the number of circulating hypodense eosinophils or a down-modulation of HLA-DR antigen (Ag) expression by T lymphocytes in peripheral blood. However, the effect of long-term therapy with inhaled glucocorticoids on peripheral blood monocytes (PBM), which are the precursors of the most numerous cell type in the lung, the alveolar macrophage, have not yet been evaluated. We therefore investigated the expression of various cell surface Ag on PBM from non-smoking patients with allergic asthma who were treated for 2.5 years with a β2-receptor agonist plus either an inhaled glucocorticoid (beclomethasone dipropionate, BDP) (n= 4) or an anticholinergic or placebo (n= 8). We compared the results with healthy volunteers (n= 7). Long-term treatment of allergic asthmatics with inhaled BDP, but not anticholinergic or placebo therapy, was associated with a significantly lower CDllb Ag expression (p< 0.04) and higher expression of CD13, CD14 and CD18 Ag (p< 0.05,p< 0.02 andp< 0.04, respectively) when compared with the healthy control subjects (n= 7). Most interestingly, PBM of asthmatics treated with inhaled BDP expressed an almost two-fold higher level of CD14 Ag on their cell surface than PBM of patients treated with anticholinergic or placebo (p< 0.03). No significant differences in the expression of CD16, CD23, CD25, CD32 and CD64 Ag or HLA-DR were observed between PBM from the different patient groups or healthy controls. Taken together, this study shows that long-term local therapy with inhaled BDP coincides with an altered expression of at least one cell surface Ag on PBM from allergic asthmatics.


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