Rheumatoid ArthritisNCT05827562
Alterations in CD8αβ and CD8αα T Cell Levels in Patients With Rheumatoid Arthritis
An observational study of Rheumatoid Arthritis, run by Assiut University.
Trial summary
To evaluate the changes in the frequencies of circulating CD4+ and CD4- T cells expressing CD8αα and CD8αβ in peripheral blood of RA patients in comparison with healthy controls. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- flow cytometry
- How many people
- 60 participants
- Where
- No sites listed yet
- Study dates
- 1 Nov 2023to Dec 2025
- 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: 30 patient with RA In addition 30 age and sex-matched healthy blood donors will be included as a control group.
Who may be able to join
- Patients with RA who fulfilled the 2010 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) revised criteria for RA (12).
- Patients having knee effusion .
Who cannot join
- Patients with autoimmune diseases other than RA. Patients or controls with tumors, infections, or other severe organ damage.
Trial locations and contacts
No sites are listed yet.
About this study
To evaluate the changes in the frequencies of circulating CD4+ and CD4- T cells expressing CD8αα and CD8αβ in peripheral blood of RA patients in comparison with healthy controls. Also, to correlate circulating and synovial fluid levels of these cells with disease activity score (DAS28) and other indices of disease severity.
Read the detailed description
Rheumatoid arthritis (RA) is a chronic, inflammatory, systemic autoimmune disease of the joints . CD4+ T cells are predominant in the synovial tissue with increased number of CD8 effector and memory T cells in synovial fluid and tissue of RA patients . CD8 functions as a dimer; including homodimer CD8αα and heterodimer CD8αβ . CD8αβ is a superior T-cell co-receptor that enhances functional avidity, CD8αα functions as a TCR corepressor to negatively regulate T cell activation . CD8αα T cells are found in human intestine and peripheral blood . CD8αα T cells increased markedly in the lesions of psoriasis where they played a pro-inflammatory role . The lower percentage of CD8αα+ mucosa associated-invariant T (MAIT) cells was found to be associated with MAIT cell dysfunction in gut immunity in necrotizing enterocolitis patients . T cells express the CD8β chain either at a high (CD8βhigh) or low density (CD8βlow ). There was a relative increase in CD8βlow cells in patients with SLE which were associated with an increased disease activity . Double positive (DP) T lymphocytes, include CD4CD8αβhigh and CD4CD8αα T cell subsets in the human blood . DP8α cells decreased in the blood and colonic mucosa of patients with inflammatory bowel disease compared with healthy individuals . CD4CD8αβhigh T cells are present at higher frequencies in some auto-immune diseases . Whether CD8αα or CD8αβ T cells contribute to the pathogenesis of RA, has not been clarified so far. investigators hypothesize that, an alteration in the frequency and distribution of these T cell subsets in RA patients might be associated with disease activity
- Conditions
- Rheumatoid Arthritis
- Being tested
- flow cytometry
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
flow cytometryDiagnostic test
Levels of circulating and synovial fluid CD4+ and CD4- T cells expressing CD8αα and CD8αβ will be assessed by flow cytometry using fluorochrome-labelled monoclonal antibodies against CD3, CD4, CD8α and CD8β surface markers. Levels of the following cells will be assessed:
- CD3+CD4-CD8αα+
- CD3+CD4-CD8α+CD8βlow
- CD3+CD4-CD8α+CD8βhigh
- CD3+CD4+CD8αβhigh
- CD3+CD4+CD8αα+
| Study group | Role | What they receive |
|---|---|---|
| patients group | . Inclusion criteria:
* Patients with RA who fulfilled the 2010 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) revised criteria for RA (1
* Patients having knee effusion .
Exclusion criteria:
* Patients with autoimmune diseases other than RA.
* Patients or controls with tumors, infections, or other severe organ damage. Receives: Diagnostic Test: flow cytometry | |
| controls group | healthy subjects Receives: Diagnostic Test: flow cytometry |
What is being measured
The primary outcome is the main question the study is designed to answer.
detection the level of circulating CD4+ and CD4- T cells expressing CD8αα and CD8αβ in peripheral blood and synovial fluid aspirates of RA patients.
The frequencies of circulating CD4+ and CD4- T cells expressing CD8αα and CD8αβ in RA patients in comparison with healthy controls. and Comparing the frequencies of these cells between peripheral blood and synovial fluid aspirates of RA patients.
Measured: baseline
Secondary outcomes (1)
numbers of patients have remission
To assess the relation between the level of these cells and numbers of patients have remission
Measured: baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2023
- Study start1 Nov 2023 (estimated)
- Primary completionNov 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies 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
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hager Ahmed Ibrahim Mohammad, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05827562
- Sponsor's protocol ID
- T cells in RA
- Status last verified
- Apr 2023
- First submitted
- 30 Mar 2023
- Last updated
- 25 Apr 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Smolen JS, Steiner G. Therapeutic strategies for rheumatoid arthritis. Nat Rev Drug Discov. 2003 Jun;2(6):473-88. doi: 10.1038/nrd1109.
PubMed 12776222Zhang F, Wei K, Slowikowski K, Fonseka CY, Rao DA, Kelly S, Goodman SM, Tabechian D, Hughes LB, Salomon-Escoto K, Watts GFM, Jonsson AH, Rangel-Moreno J, Meednu N, Rozo C, Apruzzese W, Eisenhaure TM, Lieb DJ, Boyle DL, Mandelin AM 2nd; Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Consortium; Boyce BF, DiCarlo E, Gravallese EM, Gregersen PK, Moreland L, Firestein GS, Hacohen N, Nusbaum C, Lederer JA, Perlman H, Pitzalis C, Filer A, Holers VM, Bykerk VP, Donlin LT, Anolik JH, Brenner MB, Raychaudhuri S. Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry. Nat Immunol. 2019 Jul;20(7):928-942. doi: 10.1038/s41590-019-0378-1. Epub 2019 May 6.
PubMed 31061532Wu J, Zhou C, Robertson J, Weng CC, Meistrich ML, Tailor RC, Lou YH. Identification of a bone marrow-derived CD8alphaalpha+ dendritic cell-like population in inflamed autoimmune target tissue with capability of inducing T cell apoptosis. J Leukoc Biol. 2010 Nov;88(5):849-61. doi: 10.1189/jlb.0310133. Epub 2010 Jul 13.
PubMed 20628068Qiu Y, Peng K, Liu M, Xiao W, Yang H. CD8alphaalpha TCRalphabeta Intraepithelial Lymphocytes in the Mouse Gut. Dig Dis Sci. 2016 Jun;61(6):1451-60. doi: 10.1007/s10620-015-4016-y. Epub 2016 Jan 14.
PubMed 26769056Sheng H, Marrero I, Maricic I, Fanchiang SS, Zhang S, Sant'Angelo DB, Kumar V. Distinct PLZF+CD8alphaalpha+ Unconventional T Cells Enriched in Liver Use a Cytotoxic Mechanism to Limit Autoimmunity. J Immunol. 2019 Oct 15;203(8):2150-2162. doi: 10.4049/jimmunol.1900832. Epub 2019 Sep 25.
PubMed 31554695Zhang YY, Lin YT, Wang L, Sun XW, Dang EL, Xue K, Zhang WG, Zhang KM, Wang G, Li B. CD8alphaalpha+T cells exert a pro-inflammatory role in patients with psoriasis. Skin Health Dis. 2021 Nov 16;1(4):e64. doi: 10.1002/ski2.64. eCollection 2021 Dec.
PubMed 35663772Tian J, Yan C, Jiang Y, Zhou H, Li L, Shen J, Wang J, Sun H, Yang G, Sun W. Peripheral and intestinal mucosal-associated invariant T cells in premature infants with necrotizing enterocolitis. Front Pharmacol. 2022 Sep 14;13:1008080. doi: 10.3389/fphar.2022.1008080. eCollection 2022.
PubMed 36188574Werwitzke S, Tiede A, Jacobs R, Zielinska-Skowronek M, Buyny S, Schmidt RE, Witte T. CD8alpha+beta(low) effector T cells in systemic lupus erythematosus. Scand J Immunol. 2008 May;67(5):501-8. doi: 10.1111/j.1365-3083.2008.02093.x.
PubMed 18405327Parel Y, Chizzolini C. CD4+ CD8+ double positive (DP) T cells in health and disease. Autoimmun Rev. 2004 Mar;3(3):215-20. doi: 10.1016/j.autrev.2003.09.001.
PubMed 15110234Sarrabayrouse G, Bossard C, Chauvin JM, Jarry A, Meurette G, Quevrain E, Bridonneau C, Preisser L, Asehnoune K, Labarriere N, Altare F, Sokol H, Jotereau F. CD4CD8alphaalpha lymphocytes, a novel human regulatory T cell subset induced by colonic bacteria and deficient in patients with inflammatory bowel disease. PLoS Biol. 2014 Apr 8;12(4):e1001833. doi: 10.1371/journal.pbio.1001833. eCollection 2014 Apr.
PubMed 24714093Bang K, Lund M, Wu K, Mogensen SC, Thestrup-Pedersen K. CD4+ CD8+ (thymocyte-like) T lymphocytes present in blood and skin from patients with atopic dermatitis suggest immune dysregulation. Br J Dermatol. 2001 Jun;144(6):1140-7. doi: 10.1046/j.1365-2133.2001.04223.x.
PubMed 11422033
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Alterations in CD8αβ and CD8αα T Cell Levels in Patients With Rheumatoid Arthritis
- ClinicalTrials.gov ID
- NCT05827562
- Acronym / sponsor ID
- T cells in RA
- Conditions
- Rheumatoid Arthritis
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- 1 Nov 2023 (estimated)
- Primary completion
- Nov 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 25 Apr 2023 (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 evaluate the changes in the frequencies of circulating CD4+ and CD4- T cells expressing CD8αα and CD8αβ in peripheral blood of RA patients in comparison with healthy controls. Also, to correlate circulating and synovial fluid levels of these cells with disease activity score (DAS28) and other indices of disease severity.
Detailed description
Rheumatoid arthritis (RA) is a chronic, inflammatory, systemic autoimmune disease of the joints . CD4+ T cells are predominant in the synovial tissue with increased number of CD8 effector and memory T cells in synovial fluid and tissue of RA patients . CD8 functions as a dimer; including homodimer CD8αα and heterodimer CD8αβ . CD8αβ is a superior T-cell co-receptor that enhances functional avidity, CD8αα functions as a TCR corepressor to negatively regulate T cell activation . CD8αα T cells are found in human intestine and peripheral blood . CD8αα T cells increased markedly in the lesions of psoriasis where they played a pro-inflammatory role . The lower percentage of CD8αα+ mucosa associated-invariant T (MAIT) cells was found to be associated with MAIT cell dysfunction in gut immunity in necrotizing enterocolitis patients . T cells express the CD8β chain either at a high (CD8βhigh) or low density (CD8βlow ). There was a relative increase in CD8βlow cells in patients with SLE which were associated with an increased disease activity . Double positive (DP) T lymphocytes, include CD4CD8αβhigh and CD4CD8αα T cell subsets in the human blood . DP8α cells decreased in the blood and colonic mucosa of patients with inflammatory bowel disease compared with healthy individuals . CD4CD8αβhigh T cells are present at higher frequencies in some auto-immune diseases . Whether CD8αα or CD8αβ T cells contribute to the pathogenesis of RA, has not been clarified so far. investigators hypothesize that, an alteration in the frequency and distribution of these T cell subsets in RA patients might be associated with disease activity
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| patients group | – | Diagnostic Test: flow cytometry. Inclusion criteria: * Patients with RA who fulfilled the 2010 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) revised criteria for RA (1 * Patients having knee effusion . Exclusion criteria: * Patients with autoimmune diseases other than RA. * Patients or controls with tumors, infections, or other severe organ damage. |
| controls group | – | Diagnostic Test: flow cytometryhealthy subjects |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- 30 patient with RA In addition 30 age and sex-matched healthy blood donors will be included as a control group.
Key inclusion criteria (2 listed)
- Patients with RA who fulfilled the 2010 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) revised criteria for RA (12).
- Patients having knee effusion .
Key exclusion criteria (1 listed)
- Patients with autoimmune diseases other than RA. Patients or controls with tumors, infections, or other severe organ damage.
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 cytometryLevels of circulating and synovial fluid CD4+ and CD4- T cells expressing CD8αα and CD8αβ will be assessed by flow cytometry using fluorochrome-labelled monoclonal antibodies against CD3, CD4, CD8α and CD8β surface markers. Levels of the following cells will be assessed: 1. CD3+CD4-CD8αα+ 2. CD3+CD4-CD8α+CD8βlow 3. CD3+CD4-CD8α+CD8βhigh 4. CD3+CD4+CD8αβhigh 5. CD3+CD4+CD8αα+ | Diagnostic test | controls group, patients group |
Primary outcome
detection the level of circulating CD4+ and CD4- T cells expressing CD8αα and CD8αβ in peripheral blood and synovial fluid aspirates of RA patients.
Time frame: baseline
The frequencies of circulating CD4+ and CD4- T cells expressing CD8αα and CD8αβ in RA patients in comparison with healthy controls. and Comparing the frequencies of these cells between peripheral blood and synovial fluid aspirates of RA patients.
1 secondary outcome
numbers of patients have remission
Time frame: baseline
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2023.
- Background: PubMed 12776222Smolen JS, Steiner G. Therapeutic strategies for rheumatoid arthritis. Nat Rev Drug Discov. 2003 Jun;2(6):473-88. doi: 10.1038/nrd1109.
- Background: PubMed 31061532Zhang F, Wei K, Slowikowski K, Fonseka CY, Rao DA, Kelly S, Goodman SM, Tabechian D, Hughes LB, Salomon-Escoto K, Watts GFM, Jonsson AH, Rangel-Moreno J, Meednu N, Rozo C, Apruzzese W, Eisenhaure TM, Lieb DJ, Boyle DL, Mandelin AM 2nd; Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Consortium; Boyce BF, DiCarlo E, Gravallese EM, Gregersen PK, Moreland L, Firestein GS, Hacohen N, Nusbaum C, Lederer JA, Perlman H, Pitzalis C, Filer A, Holers VM, Bykerk VP, Donlin LT, Anolik JH, Brenner MB, Raychaudhuri S. Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry. Nat Immunol. 2019 Jul;20(7):928-942. doi: 10.1038/s41590-019-0378-1. Epub 2019 May 6.
- Background: PubMed 20628068Wu J, Zhou C, Robertson J, Weng CC, Meistrich ML, Tailor RC, Lou YH. Identification of a bone marrow-derived CD8alphaalpha+ dendritic cell-like population in inflamed autoimmune target tissue with capability of inducing T cell apoptosis. J Leukoc Biol. 2010 Nov;88(5):849-61. doi: 10.1189/jlb.0310133. Epub 2010 Jul 13.
- Background: PubMed 26769056Qiu Y, Peng K, Liu M, Xiao W, Yang H. CD8alphaalpha TCRalphabeta Intraepithelial Lymphocytes in the Mouse Gut. Dig Dis Sci. 2016 Jun;61(6):1451-60. doi: 10.1007/s10620-015-4016-y. Epub 2016 Jan 14.
- Background: PubMed 31554695Sheng H, Marrero I, Maricic I, Fanchiang SS, Zhang S, Sant'Angelo DB, Kumar V. Distinct PLZF+CD8alphaalpha+ Unconventional T Cells Enriched in Liver Use a Cytotoxic Mechanism to Limit Autoimmunity. J Immunol. 2019 Oct 15;203(8):2150-2162. doi: 10.4049/jimmunol.1900832. Epub 2019 Sep 25.
- Background: PubMed 35663772Zhang YY, Lin YT, Wang L, Sun XW, Dang EL, Xue K, Zhang WG, Zhang KM, Wang G, Li B. CD8alphaalpha+T cells exert a pro-inflammatory role in patients with psoriasis. Skin Health Dis. 2021 Nov 16;1(4):e64. doi: 10.1002/ski2.64. eCollection 2021 Dec.
- Background: PubMed 36188574Tian J, Yan C, Jiang Y, Zhou H, Li L, Shen J, Wang J, Sun H, Yang G, Sun W. Peripheral and intestinal mucosal-associated invariant T cells in premature infants with necrotizing enterocolitis. Front Pharmacol. 2022 Sep 14;13:1008080. doi: 10.3389/fphar.2022.1008080. eCollection 2022.
- Background: PubMed 18405327Werwitzke S, Tiede A, Jacobs R, Zielinska-Skowronek M, Buyny S, Schmidt RE, Witte T. CD8alpha+beta(low) effector T cells in systemic lupus erythematosus. Scand J Immunol. 2008 May;67(5):501-8. doi: 10.1111/j.1365-3083.2008.02093.x.
- Background: PubMed 15110234Parel Y, Chizzolini C. CD4+ CD8+ double positive (DP) T cells in health and disease. Autoimmun Rev. 2004 Mar;3(3):215-20. doi: 10.1016/j.autrev.2003.09.001.
- Background: PubMed 24714093Sarrabayrouse G, Bossard C, Chauvin JM, Jarry A, Meurette G, Quevrain E, Bridonneau C, Preisser L, Asehnoune K, Labarriere N, Altare F, Sokol H, Jotereau F. CD4CD8alphaalpha lymphocytes, a novel human regulatory T cell subset induced by colonic bacteria and deficient in patients with inflammatory bowel disease. PLoS Biol. 2014 Apr 8;12(4):e1001833. doi: 10.1371/journal.pbio.1001833. eCollection 2014 Apr.
- Background: PubMed 11422033Bang K, Lund M, Wu K, Mogensen SC, Thestrup-Pedersen K. CD4+ CD8+ (thymocyte-like) T lymphocytes present in blood and skin from patients with atopic dermatitis suggest immune dysregulation. Br J Dermatol. 2001 Jun;144(6):1140-7. doi: 10.1046/j.1365-2133.2001.04223.x.
Related trials for Rheumatoid Arthritis
RecruitingPhase 2
Study of PTC844 in Participants With Active Rheumatoid Arthritis
Rheumatoid Arthritis
Not yet recruitingPhase 1
An Ascending Dose Study of DKB903 in Participants With Rheumatoid Arthritis (RA) and Participants With Systemic Lupus Erythematosus (SLE)
Rheumatoid Arthritis and Systemic Lupus Erythematosus
Not yet recruitingPhase 1
R-2487 in Patients With Sjogren's Syndrome (SjD)
Sjogren's Syndrome, Sjögren
RecruitingPhase 1
A Trial in Healthy Adult Participants and Adults With Autoimmune Diseases to Test How HBM7020 is Tolerated and How it Behaves in the Body
Rheumatoid Arthritis, Systemic Lupus Erythematosus
Active, not recruitingPhase 2
A Study Evaluating the Safety and Efficacy of Inhaled AP01 in Participants With Progressive Pulmonary Fibrosis
Pulmonary Fibrosis, Progressive Pulmonary Fibrosis
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 Rheumatoid Arthritis, 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 25 Apr 2023. 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 Hager Mohammad, Demonstrator (01144867843, hager222.eg@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
detection the level of circulating CD4+ and CD4- T cells expressing CD8αα and CD8αβ in peripheral blood and synovial fluid aspirates of RA patients. (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 NCT05827562, which also lists 11 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 25 Apr 2023.