Lymphoproliferative DisordersCD19NCT04734470
Expression of CD19 Complex in Lymphoproliferative Disorders
An observational study of Lymphoproliferative Disorders, run by Assiut University.
Trial summary
1. To study the expression pattern of CD19(cluster of differentiation antigen19) complex in lymphoproliferative disorders and its diagnostic value. 2. To investigate the biological significance of CD19 complex expression in lymphoproliferative disorders. 3. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Lymphoproliferative Disorders
- What is being tested?
- Flow cytometry
- How many people
- 92 participants
- Where
- No sites listed yet
- Study dates
- Mar 2021to Apr 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: The sample size is 92 (46 in each arm) but number of controls will be decreased and number of cases will be increased.
Who may be able to join
- Patients with acute lymphoproliferative disorders.
- Patients with chronic lymphoproliferative disorders
Who cannot join
- patients with non lymphoid disorders.
Trial locations and contacts
No sites are listed yet.
About this study
- To study the expression pattern of CD19(cluster of differentiation antigen19) complex in lymphoproliferative disorders and its diagnostic value.
- To investigate the biological significance of CD19 complex expression in lymphoproliferative disorders.
- To explore the possibility of ectopic expression of CD19 complex in non B-lineage lymphoproliferative disorders.
Read the detailed description
Lymphoproliferative disorders (LPD)comprise a heterogeneous group of diseases characterized by uncontrolled production of lymphocytes that cause monoclonal lymphocytosis, lymphadenopathy and bone marrow infiltration.They Typically occur in people who have a compromised immune system with highly variable clinical course.
Lymphoproliferative disorders are immunomorphologically and clinically heterogeneous. The two major types of lymphocytes are B cells and T cells, which are derived from pluripotent hematopoietic stem cells in the bone marrow.
Lymphoproliferative disorders include; Follicular lymphoma, chronic lymphocytic leukemia, acute lymphoblastic leukemia, hairy cell leukemia, Hemophagocytic lymphohistiocytosis (HLH), B-cell lymphomas, T-cell lymphomas, multiple myeloma, Waldenström's macroglobulinemia, Wiskott Aldrich syndrome, Langerhans cell histiocytosis (LCH), Lymphocyte-variant hypereosinophilia, Pityriasis Lichenoides, post-transplant lymphoproliferative disorder, autoimmune lymphoproliferative syndrome (ALPS), Lymphoid interstitial pneumonia, Epstein Barr virus associated lymphoproliferative diseases, Castleman disease and X-linked lymphoproliferative disease.
Many patients are asymptomatic at the time of first presentation, with the diagnosis being made as an incidental finding after a routine medical examination or blood test, for example, complete blood count (CBC).
Definitive diagnosis is made on the characteristic lymphocyte morphology and immunophenotype usually from samples of peripheral blood ,bone marrow samples or lymph nodes.
The membrane receptor proteins (CD19, CD81, CD21 (complement receptor type2) and Leu-13(CD225)), form a complex (CD19 complex) on human B lymphocytes that has costimulatory activity for the antigen receptor, membrane IgM(mIgM) .The complex is unique among known membrane protein complexes of the immune system because its components represent different protein families, and can be expressed individually.
The biochemical mechanism by which the complex costimulates is not understood.CD19 has been shown to be a major substrate of a protein tyrosine kinase activated by mIgM, and tyrosine phosphorylated CD19 binds phosphatidylinositol 3-kinase (PI3-kinase), an enzyme that is required for the cellular activating effects of certain receptor tyrosine kinases. Thus, several biochemical pathways may be triggered by the CD21/CD19/CD81/CD225 complex that relate to its role in amplifying the response of B cells to antigen.
Multiple biologic effects of the CD21/CD19/ CD81/CD225 complex may reflect the discrete actions of individual components, each of which is a member of a distinct protein family: CD21 of the regulators of complement activation family; CD19 of the Ig superfamily;and CD81 of the tetraspan family of membrane proteins and is an important regulator of B-cell signaling. CD225 of Interferon-induced transmembrane protein (IFITM) family.
Although CD19 function may be elicited following its potential binding to an as yet unidentified ligand, C3d binding to CD21 supplies an already characterized ligand for the CD19 complex, thereby linking complement immune responses and the generation of immunological activation and B cell function.
Ligation of members of the CD19 complex initiates a cascade of biological responses that can modulate signal transduction through the B cell Ag-receptor complex and other cell surface receptors. So it may help in understanding the signal transduction pathways through this complex.
- Conditions
- Lymphoproliferative Disorders
- Being tested
- Flow cytometry
- Medical subject headings
- Lymphoproliferative Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Flow cytometryDiagnostic test
The study of CD19 complex expression in lymphoproliferative disorders by flowcytometry
What is being measured
The primary outcome is the main question the study is designed to answer.
To study the expression pattern of CD19 complex in lymphoproliferative disorders and its diagnostic value.
Study of CD19 complex expression pattern in lymphoproliferative disorders by flow cytometry
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2021
- Study startMar 2021 (estimated)
- Primary completionMar 2023 (estimated)
- Study completionApr 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Lymphoproliferative DisordersStudies of the same condition, open and under way.
- More trials run by Assiut UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Retrospective
- Enrolment
- 92 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mahran mohamed hussein mahran, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04734470
- Sponsor's protocol ID
- Expression of CD19 complex
- Acronym
- CD19
- Status last verified
- Feb 2021
- First submitted
- 28 Jan 2021
- Last updated
- 4 Feb 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Goede V, Fischer K, Busch R, Engelke A, Eichhorst B, Wendtner CM, Chagorova T, de la Serna J, Dilhuydy MS, Illmer T, Opat S, Owen CJ, Samoylova O, Kreuzer KA, Stilgenbauer S, Dohner H, Langerak AW, Ritgen M, Kneba M, Asikanius E, Humphrey K, Wenger M, Hallek M. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med. 2014 Mar 20;370(12):1101-10. doi: 10.1056/NEJMoa1313984. Epub 2014 Jan 8.
PubMed 24401022Zavala-Vega S, Palma-Lara I, Ortega-Soto E, Trejo-Solis C, de Arellano IT, Ucharima-Corona LE, Garcia-Chacon G, Ochoa SA, Xicohtencatl-Cortes J, Cruz-Cordova A, Luna-Pineda VM, Jimenez-Hernandez E, Vazquez-Meraz E, Mejia-Arangure JM, Guzman-Bucio S, Rembao-Bojorquez D, Sanchez-Gomez C, Salazar-Garcia M, Arellano-Galindo J. Role of Epstein-Barr Virus in Glioblastoma. Crit Rev Oncog. 2019;24(4):307-338. doi: 10.1615/CritRevOncog.2019032655.
PubMed 32421988Vaillant AAJ, Stang CM. Lymphoproliferative Disorders. StatPearls [Internet]: StatPearls Publishing; 2020.
Zheng YY, Chen G, Zhou XG, Jin Y, Xie JL, Zhang SH, Zhang YN. [Retrospective analysis of 4 cases of the so-called blastic NK-cell lymphoma, with reference to the 2008 WHO classification of tumours of haematopoietic and lymphoid tissues]. Zhonghua Bing Li Xue Za Zhi. 2010 Sep;39(9):600-5. Chinese.
PubMed 21092587Byrd JC, Brown JR, O'Brien S, Barrientos JC, Kay NE, Reddy NM, Coutre S, Tam CS, Mulligan SP, Jaeger U, Devereux S, Barr PM, Furman RR, Kipps TJ, Cymbalista F, Pocock C, Thornton P, Caligaris-Cappio F, Robak T, Delgado J, Schuster SJ, Montillo M, Schuh A, de Vos S, Gill D, Bloor A, Dearden C, Moreno C, Jones JJ, Chu AD, Fardis M, McGreivy J, Clow F, James DF, Hillmen P; RESONATE Investigators. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med. 2014 Jul 17;371(3):213-23. doi: 10.1056/NEJMoa1400376. Epub 2014 May 31.
PubMed 24881631van Zelm MC, Reisli I. CD19 Deficiency due to Genetic Defects in the CD19 and CD81 Genes. Humoral Primary Immunodeficiencies: Springer; 2019. p. 83-95.
Pongas GN, Annunziata CM, Staudt LM. PI3Kdelta inhibition causes feedback activation of PI3Kalpha in the ABC subtype of diffuse large B-cell lymphoma. Oncotarget. 2017 Sep 13;8(47):81794-81802. doi: 10.18632/oncotarget.20864. eCollection 2017 Oct 10.
PubMed 29137222Dasgupta S, Dasgupta S, Bandyopadhyay M. Regulatory B cells in infection, inflammation, and autoimmunity. Cell Immunol. 2020 Jun;352:104076. doi: 10.1016/j.cellimm.2020.104076. Epub 2020 Feb 27.
PubMed 32143836Feingold JM, Ungar DR. DOSAGE REGIMES FOR THE ADMINISTRATION OF AN ANTI-CD19 ADC. US Patent App. 16/622,649; 2020.
Beckwith KA, Byrd JC, Muthusamy N. Tetraspanins as therapeutic targets in hematological malignancy: a concise review. Front Physiol. 2015 Mar 23;6:91. doi: 10.3389/fphys.2015.00091. eCollection 2015.
PubMed 25852576Yanez DC, Ross S, Crompton T. The IFITM protein family in adaptive immunity. Immunology. 2020 Apr;159(4):365-372. doi: 10.1111/imm.13163. Epub 2019 Dec 22.
PubMed 31792954Carroll MC. The complement system in B cell regulation. Mol Immunol. 2004 Jun;41(2-3):141-6. doi: 10.1016/j.molimm.2004.03.017.
PubMed 15159059Tedder TF, Poe JC, Fujimoto M, Haas KM, Sato S. The CD19-CD21 signal transduction complex of B lymphocytes regulates the balance between health and autoimmune disease: systemic sclerosis as a model system. Curr Dir Autoimmun. 2005;8:55-90. doi: 10.1159/000082087.
PubMed 15564717
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Expression of CD19 Complex in Lymphoproliferative Disorders
- ClinicalTrials.gov ID
- NCT04734470
- Acronym / sponsor ID
- CD19 / Expression of CD19 complex
- Conditions
- Lymphoproliferative Disorders
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 92 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- Mar 2021 (estimated)
- Primary completion
- Mar 2023 (estimated)
- Study completion
- Apr 2023 (estimated)
- First posted
- 2 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
- To study the expression pattern of CD19(cluster of differentiation antigen19) complex in lymphoproliferative disorders and its diagnostic value.
- To investigate the biological significance of CD19 complex expression in lymphoproliferative disorders.
- To explore the possibility of ectopic expression of CD19 complex in non B-lineage lymphoproliferative disorders.
Detailed description
Lymphoproliferative disorders (LPD)comprise a heterogeneous group of diseases characterized by uncontrolled production of lymphocytes that cause monoclonal lymphocytosis, lymphadenopathy and bone marrow infiltration.They Typically occur in people who have a compromised immune system with highly variable clinical course.
Lymphoproliferative disorders are immunomorphologically and clinically heterogeneous. The two major types of lymphocytes are B cells and T cells, which are derived from pluripotent hematopoietic stem cells in the bone marrow.
Lymphoproliferative disorders include; Follicular lymphoma, chronic lymphocytic leukemia, acute lymphoblastic leukemia, hairy cell leukemia, Hemophagocytic lymphohistiocytosis (HLH), B-cell lymphomas, T-cell lymphomas, multiple myeloma, Waldenström's macroglobulinemia, Wiskott Aldrich syndrome, Langerhans cell histiocytosis (LCH), Lymphocyte-variant hypereosinophilia, Pityriasis Lichenoides, post-transplant lymphoproliferative disorder, autoimmune lymphoproliferative syndrome (ALPS), Lymphoid interstitial pneumonia, Epstein Barr virus associated lymphoproliferative diseases, Castleman disease and X-linked lymphoproliferative disease.
Many patients are asymptomatic at the time of first presentation, with the diagnosis being made as an incidental finding after a routine medical examination or blood test, for example, complete blood count (CBC).
Definitive diagnosis is made on the characteristic lymphocyte morphology and immunophenotype usually from samples of peripheral blood ,bone marrow samples or lymph nodes.
The membrane receptor proteins (CD19, CD81, CD21 (complement receptor type2) and Leu-13(CD225)), form a complex (CD19 complex) on human B lymphocytes that has costimulatory activity for the antigen receptor, membrane IgM(mIgM) .The complex is unique among known membrane protein complexes of the immune system because its components represent different protein families, and can be expressed individually.
The biochemical mechanism by which the complex costimulates is not understood.CD19 has been shown to be a major substrate of a protein tyrosine kinase activated by mIgM, and tyrosine phosphorylated CD19 binds phosphatidylinositol 3-kinase (PI3-kinase), an enzyme that is required for the cellular activating effects of certain receptor tyrosine kinases. Thus, several biochemical pathways may be triggered by the CD21/CD19/CD81/CD225 complex that relate to its role in amplifying the response of B cells to antigen.
Multiple biologic effects of the CD21/CD19/ CD81/CD225 complex may reflect the discrete actions of individual components, each of which is a member of a distinct protein family: CD21 of the regulators of complement activation family; CD19 of the Ig superfamily;and CD81 of the tetraspan family of membrane proteins and is an important regulator of B-cell signaling. CD225 of Interferon-induced transmembrane protein (IFITM) family.
Although CD19 function may be elicited following its potential binding to an as yet unidentified ligand, C3d binding to CD21 supplies an already characterized ligand for the CD19 complex, thereby linking complement immune responses and the generation of immunological activation and B cell function.
Ligation of members of the CD19 complex initiates a cascade of biological responses that can modulate signal transduction through the B cell Ag-receptor complex and other cell surface receptors. So it may help in understanding the signal transduction pathways through this complex.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- The sample size is 92 (46 in each arm) but number of controls will be decreased and number of cases will be increased.
Key inclusion criteria (2 listed)
- Patients with acute lymphoproliferative disorders.
- Patients with chronic lymphoproliferative disorders
Key exclusion criteria (1 listed)
- patients with non lymphoid disorders.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Flow cytometryThe study of CD19 complex expression in lymphoproliferative disorders by flowcytometry | Diagnostic test | – |
Primary outcome
To study the expression pattern of CD19 complex in lymphoproliferative disorders and its diagnostic value.
Time frame: Baseline
Study of CD19 complex expression pattern in lymphoproliferative disorders by flow cytometry
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2021.
- Background: PubMed 24401022Goede V, Fischer K, Busch R, Engelke A, Eichhorst B, Wendtner CM, Chagorova T, de la Serna J, Dilhuydy MS, Illmer T, Opat S, Owen CJ, Samoylova O, Kreuzer KA, Stilgenbauer S, Dohner H, Langerak AW, Ritgen M, Kneba M, Asikanius E, Humphrey K, Wenger M, Hallek M. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med. 2014 Mar 20;370(12):1101-10. doi: 10.1056/NEJMoa1313984. Epub 2014 Jan 8.
- Background: PubMed 32421988Zavala-Vega S, Palma-Lara I, Ortega-Soto E, Trejo-Solis C, de Arellano IT, Ucharima-Corona LE, Garcia-Chacon G, Ochoa SA, Xicohtencatl-Cortes J, Cruz-Cordova A, Luna-Pineda VM, Jimenez-Hernandez E, Vazquez-Meraz E, Mejia-Arangure JM, Guzman-Bucio S, Rembao-Bojorquez D, Sanchez-Gomez C, Salazar-Garcia M, Arellano-Galindo J. Role of Epstein-Barr Virus in Glioblastoma. Crit Rev Oncog. 2019;24(4):307-338. doi: 10.1615/CritRevOncog.2019032655.
- BackgroundVaillant AAJ, Stang CM. Lymphoproliferative Disorders. StatPearls [Internet]: StatPearls Publishing; 2020.
- Background: PubMed 21092587Zheng YY, Chen G, Zhou XG, Jin Y, Xie JL, Zhang SH, Zhang YN. [Retrospective analysis of 4 cases of the so-called blastic NK-cell lymphoma, with reference to the 2008 WHO classification of tumours of haematopoietic and lymphoid tissues]. Zhonghua Bing Li Xue Za Zhi. 2010 Sep;39(9):600-5. Chinese.
- Background: PubMed 24881631Byrd JC, Brown JR, O'Brien S, Barrientos JC, Kay NE, Reddy NM, Coutre S, Tam CS, Mulligan SP, Jaeger U, Devereux S, Barr PM, Furman RR, Kipps TJ, Cymbalista F, Pocock C, Thornton P, Caligaris-Cappio F, Robak T, Delgado J, Schuster SJ, Montillo M, Schuh A, de Vos S, Gill D, Bloor A, Dearden C, Moreno C, Jones JJ, Chu AD, Fardis M, McGreivy J, Clow F, James DF, Hillmen P; RESONATE Investigators. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med. 2014 Jul 17;371(3):213-23. doi: 10.1056/NEJMoa1400376. Epub 2014 May 31.
- Backgroundvan Zelm MC, Reisli I. CD19 Deficiency due to Genetic Defects in the CD19 and CD81 Genes. Humoral Primary Immunodeficiencies: Springer; 2019. p. 83-95.
- Background: PubMed 29137222Pongas GN, Annunziata CM, Staudt LM. PI3Kdelta inhibition causes feedback activation of PI3Kalpha in the ABC subtype of diffuse large B-cell lymphoma. Oncotarget. 2017 Sep 13;8(47):81794-81802. doi: 10.18632/oncotarget.20864. eCollection 2017 Oct 10.
- Background: PubMed 32143836Dasgupta S, Dasgupta S, Bandyopadhyay M. Regulatory B cells in infection, inflammation, and autoimmunity. Cell Immunol. 2020 Jun;352:104076. doi: 10.1016/j.cellimm.2020.104076. Epub 2020 Feb 27.
- BackgroundFeingold JM, Ungar DR. DOSAGE REGIMES FOR THE ADMINISTRATION OF AN ANTI-CD19 ADC. US Patent App. 16/622,649; 2020.
- Background: PubMed 25852576Beckwith KA, Byrd JC, Muthusamy N. Tetraspanins as therapeutic targets in hematological malignancy: a concise review. Front Physiol. 2015 Mar 23;6:91. doi: 10.3389/fphys.2015.00091. eCollection 2015.
- Background: PubMed 31792954Yanez DC, Ross S, Crompton T. The IFITM protein family in adaptive immunity. Immunology. 2020 Apr;159(4):365-372. doi: 10.1111/imm.13163. Epub 2019 Dec 22.
- Background: PubMed 15159059Carroll MC. The complement system in B cell regulation. Mol Immunol. 2004 Jun;41(2-3):141-6. doi: 10.1016/j.molimm.2004.03.017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Questions about this trial
What is this clinical trial studying?
An observational study of Lymphoproliferative Disorders, run by Assiut University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 4 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Mahran Mohamed Hussein, Assistant Lecturer (01028444857, Mahran_Morsy@med.aun.edu.eg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To study the expression pattern of CD19 complex in lymphoproliferative disorders and its diagnostic value. (time frame: Baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04734470, which also lists 13 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2021.