Humoral Immune Responses Against the Oncofetal-Antigen/Immature Laminin Receptor (OFA/iLR) in Patients with Chronic Lymphocytic Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2820-2820
Author(s):  
Birte Friedrichs ◽  
Sandra Siegel ◽  
Norbert Schmitz ◽  
Matthias Zeis
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Immune Responses ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
Laminin Receptor ◽  
Enzyme Linked Immunosorbent Assay ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
B Cell Subsets

Abstract The 37 kD oncofetal antigen/immature laminin receptor (OFA/iLR) is a strongly overexpressed tumor antigen on malignant cells of numerous tumor entities including several hematological malignancies but it is not present on the cell surface of normal differentiated tissues. OFA/iLR is widely expressed on chronic lymphocytic leukemia (CLL) cells while absent on different normal B-cell subsets. The aim of this study was to evaluate and characterize humoral immune responses towards OFA/iLR in patients with CLL. 38 healthy individuals and 68 untreated patients with chronic lymphocytic leukemia were analysed for the presence of anti-OFA/iLR-antibodies. Sera were screened in an enzyme-linked immunosorbent assay (ELISA) for immunoglobulin G (IgG) and IgM anti-OFA/iLR-antibodies. Detectable IgG or IgM responses to OFA protein were present in 32 of 68 patients (47,0%) but only in 4 of 38 (10,5%) healthy donors. IgG subtype analysis revealed a predominant IgG1 and IgG3 response. Utilizing 42 peptides deduced from the complete OFA/iLR amino acid sequence, 24 (35,3%) samples with significant anti-OFA/iLR IgG and/or IgM titers were also reactive with at least one OFA/iLR epitope. Patient-derived anti-OFA/iLR antibodies were capable of recognizing and selectively killing OFA/iLR expressing CLL cells in complement-mediated and antibody-dependent cellular cytotoxicity (ADCC) assays. Kaplan-Meier plots for progression-free survival (PFS) revealed a tendendy for longer PFS in patients with detectable humoral responses compared patients with negative ELISA (p=0,0165). In addition, sera from eight CLL patients who had undergone allogeneic hematopoetic stem cell transplantion (allo-HSCT) were analysed. Six out of eight patients showed high values for IgG or IgM anti-OFA/iLR-antibodies after allo-HSCT as long as remaining in complete remission suggesting a potential role of anti-OFA/iLR-directed Graft-versus-Leukemia effects. For the first time, these data suggest that anti-OFA/iLR antibodies might be involved in the immunological control of OFA/iLR expressing CLL cells in vivo.

scholarly journals Humoral immune responses toward tumor-derived antigens in previously untreated patients with chronic lymphocytic leukemia

Oncotarget ◽  
2016 ◽  
Vol 8 (2) ◽  
pp. 3274-3288 ◽  
Author(s):  
Valentina Griggio ◽  
Giorgia Mandili ◽  
Candida Vitale ◽  
Michela Capello ◽  
Paolo Macor ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Immune Responses ◽  
Lymphocytic Leukemia ◽  
Humoral Immune ◽  
Humoral Immune Responses

scholarly journals Idiotypes of anti-Ia antibodies. I. Expression of the 14-4-4S idiotype in humoral immune responses.

1981 ◽  
Vol 154 (2) ◽  
pp. 397-409 ◽  
Author(s):  
S L Epstein ◽  
K Ozato ◽  
J A Bluestone ◽  
D H Sachs
Keyword(s):  
Immune Responses ◽  
Immunosorbent Assay ◽  
Heavy Chain ◽  
Antigenic Specificity ◽  
Enzyme Linked Immunosorbent Assay ◽  
Absorption Analysis ◽  
Specific Enzyme ◽  
Cellular Receptors ◽  
Humoral Immune ◽  
Humoral Immune Responses

The idiotype of a mouse monoclonal anti-I-E antibody, 14-4-4S, has been studied using a heterologous anti-idiotypic reagent. This antibody recognizes Ia. 7, an antigenic specificity present in all strains expressing a product of the I-E subregion. Expression of the 14-4-4S idiotype in humoral immune responses was analyzed by an idiotype-specific enzyme-linked immunosorbent assay system. The idiotype was readily detectable in C3H.SW anti-C3H alloantisera, the same immunization combination from which the hybridoma was derived. Absorption analysis demonstrated the anti-I-E specificity of the idiotype-positive molecules in these alloantisera. Penetrance of idiotype expression was high among individual C3H.SW immune mice (9 of 10 tested). To examine genetic requirements for idiotype expression, an immunization was performed using as responders CWB mice, congenic with C3H.SW but differing at the heavy chain allotype loci. Immune sera of individual CWB mice contained very little or no idiotype, demonstrating that levels of idiotype expression are influenced by allotype-linked genes, although the influence of other genes has not been ruled. The 14-4-4S idiotype therefore represents a shared idiotype of anti-Ia antibodies and provides opportunities for analysis of the idiotypes of cellular receptors for the corresponding Ia antigen.

In vivo inhibition of cell-mediated and humoral immune responses to cellular antigens by SV-IV, a major protein secreted from the rat seminal vesicle epithelium

1995 ◽  
Vol 28 (1) ◽  
pp. 15-30 ◽  
Author(s):  
Caterina Romano-Carratelli ◽  
Marilena Galdiero ◽  
Immacolata Nuzzo ◽  
Concetta Bentivoglio ◽  
Raffaele Porta ◽  
...  
Keyword(s):  
Immune Responses ◽  
Seminal Vesicle ◽  
Major Protein ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Rat Seminal Vesicle

Chondroitin sulfate activates B cells in vitro, expands CD138+cells in vivo, and interferes with established humoral immune responses

2014 ◽  
Vol 96 (1) ◽  
pp. 65-72 ◽  
Author(s):  
Hilke Brühl ◽  
Josef Cihak ◽  
Nicole Goebel ◽  
Yvonne Talke ◽  
Kerstin Renner ◽  
...  
Keyword(s):  
B Cells ◽  
Immune Responses ◽  
Chondroitin Sulfate ◽  
Humoral Immune ◽  
Humoral Immune Responses

scholarly journals Functional and clinical relevance of VLA-4 (CD49d/CD29) in ibrutinib-treated chronic lymphocytic leukemia

2018 ◽  
Vol 215 (2) ◽  
pp. 681-697 ◽  
Author(s):  
Erika Tissino ◽  
Dania Benedetti ◽  
Sarah E.M. Herman ◽  
Elisa ten Hacken ◽  
Inhye E. Ahn ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Progression Free Survival ◽  
Cell Receptor ◽  
Lymphocytic Leukemia ◽  
Clinical Activity ◽  
Independent Manner ◽  
Btk Inhibitor

The Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib, which antagonizes B cell receptor (BCR) signals, demonstrates remarkable clinical activity in chronic lymphocytic leukemia (CLL). The lymphocytosis experienced by most patients under ibrutinib has previously been attributed to inhibition of BTK-dependent integrin and chemokine cues operating to retain the tumor cells in nodal compartments. Here, we show that the VLA-4 integrin, as expressed by CD49d-positive CLL, can be inside-out activated upon BCR triggering, thus reinforcing the adhesive capacities of CLL cells. In vitro and in vivo ibrutinib treatment, although reducing the constitutive VLA-4 activation and cell adhesion, can be overcome by exogenous BCR triggering in a BTK-independent manner involving PI3K. Clinically, in three independent ibrutinib-treated CLL cohorts, CD49d expression identifies cases with reduced lymphocytosis and inferior nodal response and behaves as independent predictor of shorter progression-free survival, suggesting the retention of CD49d-expressing CLL cells in tissue sites via activated VLA-4. Evaluation of CD49d expression should be incorporated in the characterization of CLL undergoing therapy with BCR inhibitors.

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