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Cause of Scleroderma: B Cells and T Cells

Author: Shelley Ensz. Scleroderma is highly variable. See Types of Scleroderma. Read Disclaimer
Overview of B Cells and T Cells
B Cells and T-Cells and Autoimmunity
B Cells and T Cells and Systemic Sclerosis

Overview of B Cells and T Cells

T cells are white blood cells that help stimulate an immune response to infections. In the thymus gland, lympohocytes are matured into T cells. Sometimes T cells become overactive, which is suspected as being part of the process that leads to autoimmune diseases. (Also see Causes of Scleroderma, What is Scleroderma?, Types of Scleroderma, and Systemic Sclerosis)

B Cells and T Cells.The white blood cells involved in the acquired immune response are called 'lymphocytes'. There are two main types of lymphocytes - B cells and T cells. B and T lymphocytes are made in the bone marrow, like the other blood cells. They have to fully mature before they can help in the immune response. T cells travel through the blood stream to the thymus gland where they become fully developed. Once they are fully mature, they travel to the spleen and lymph nodes, ready to fight infection. Cancer Research UK.

Thymus. The thymus is a ductless gland located in the upper anterior portion of the chest cavity. It is most active during puberty, after which it shrinks in size and activity in most individuals and is replaced with fat. The thymus plays an important role in the development of the immune system in early life, and its cells form a part of the body's normal immune system. Wikepedia.

New Gene Treatment Effective for Some Leukemia Patients. A new way of genetically altering a patient’s cells to fight cancer has helped desperately ill people with leukemia when every other treatment had failed, researchers reported. New York Times, 11/20/2017. (Also see Cancer)

B Cells and T Cells and Autoimmunity

Type 2 Polarized T Cell Phenotype is Associated with Methotrexate (MTX) Non-response in Patients with Rheumatoid Arthritis (RA). MTX-non-responsive RA patients exhibit a bias towards type 2-polarized T cell inflammatory responses. PubMed, Arthritis Rheumatol, 02/10/2020. (Also see Diagnosis of Rheumatoid Arthritis and Immunosuppressants)

B cell synovitis and clinical phenotypes in rheumatoid arthritis: relationship to disease stages and drug exposure. We demonstrate an ongoing B cell-rich synovitis in a larger proportion of patients with established RA that does not seem to be captured by standard clinimetric assessment. PubMed, Arthritis Rheumatol, 11/29/2019. (Also see Diagnosis of Rheumatoid Arthritis)

Imbalance between CD8+CD28+ and CD8+CD28- T-cell subsets and its clinical significance in patients with systemic lupus erythematosus. These data suggest that high expression of Fas, FasL and IL-6 and low expression of CTLA-4 by the CD8+CD28+ T-cell subset promotes the activation-induced cell death of the CD8+CD28+ T-cell subset. PubMed, Lupus, 2019 Aug 9:961203319867130. (Also see Causes of Lupus)

Depletion of PD-1-positive cells ameliorates autoimmune disease. The targeted depletion of PD-1-expressing cells contingent to the preservation of adaptive immunity might be effective in the treatment of a wide range of autoimmune diseases. Nature Biomedical Engineering, 03/04/2019.

Deltex1 (DTX1) suppresses T cell function and is a biomarker for diagnosis and disease activity of systemic lupus erythematosus (SLE). DTX1 expression in the peripheral blood mononuclear cells was significantly lower in SLE patients and had an inverse correlation with disease activity, indicating that the DTX1 level may be a good disease marker of SLE. PubMed, Rheumatology (Oxford), 01/09/2019. (Also see Diagnosis of Lupus)

Aberrant T cell subsets and cytokines expression profile in systemic lupus erythematosus (SLE). T cell subsets and levels of chemokines and cytokines in patients with SLE and their relationships between disease activity and organ involvement were assessed. PubMed, Clin Rheumatol, 2018 Sep;37(9):2405-2413. (Also see Causes of Lupus)

B-cell activity markers are associated with different disease activity domains in primary Sjögren's syndrome. All biomarkers were associated with total EULAR Sjögren's Syndrome Disease Activity Index scores but with differing domain associations. PubMed, Rheumatology (Oxford), 03/28/2018. (Also see Sjögren's Syndrome Research)

Lipodystrophy (LD) and obesity are associated with decreased number of T cells with regulatory function and pro–inflammatory macrophage phenotype. LD and obesity are associated with changes in the immune system: a significant reduction in the number of T cells with regulatory function and a shift of monocyteo–derived macrophages towards lipid accumulation. PubMed, Int J Obes (Lond), 2017 Nov;41(11):1676-1684. (Also see Lipodystrophy)

Lupus nephritis and B–cell targeting therapy. The combination of different targeted approaches as well as a focus on new clinical end–points may be strategies to identify new therapeutic options. PubMed, Expert Rev Clin Immunol, 08/11/2017. (Also see Treatments for Lupus)

Dominant B cell receptor (BCR) clones in peripheral blood predict onset of arthritis in individuals at risk for rheumatoid arthritis. Dominant BCR clones in peripheral blood predict onset of clinical signs and symptoms of RA in at–risk individuals with high accuracy. PubMed, Ann Rheum Dis, 08/08/2017.

Predicting and managing primary and secondary non-response to rituximab using B-cell biomarkers in systemic lupus erythematosus. Treatment with anti–CD20 agents can be guided by B-cell monitoring and should aim to achieve complete depletion. PubMed, Ann Rheum Dis, 07/06/2017. (Also see Treatments for Lupus)

Expression of CCR6 on B cells in systemic lupus erythematosus patients. Pre–germinal centre B cells are found in lower proportions and the expression of CCR6 is increased on B cells of SLE patients, suggesting a role for the chemokine pair in the pathogenesis of the disease. PubMed, Clin Rheumatol, 2017 Jun;36(6):1453-1456. (Also see Causes of Lupus)

Analysis of the CD161–expressing cell quantities and CD161 expression levels in peripheral blood natural killer (NK) and T cells of systemic lupus erythematosus patients. Our results indicated that CD161–expressing cell frequency and the CD161 expression levels were reduced in some NK and T cell subpopulations of SLE patients, suggesting possible important role of CD161 and CD161–expressing immune cells in the SLE pathogenesis. PubMed, Clin Exp Med, 2017 Feb;17(1):101-109. (Also see Natural Killer Cells)

B and T Cells and Systemic Sclerosis (SSc, Scleroderma)

CD21low B cells in systemic sclerosis: A possible marker of vascular complications. CD21low B cells are increased in SSc patients with visceral vascular manifestations. PubMed, Clin Immunol, 2020 Apr;213:108364. (Also see Vascular Involvement)

B cell depletion treatment decreases CD4+IL4+ and CD4+CD40L+ T cells in patients with systemic sclerosis (SSc). Our study demonstrates a link between rituximab treatment and CD4+IL4+ T cell decrease both in the skin and peripheral blood of patients with SSc. PubMed, Rheumatol Int, 06/21/2019. (Also see Biologic Agents)

Skin resident memory T cell population is not effectively constructed in systemic sclerosis. Regarding the contribution of circulating T cells, over–production of IL-13 by circulating effector/memory T cells is reported to be critical for more severe cutaneous disease. PubMed, Br J Dermatol, 08/18/2018.

B cell activating factor (BAFF) inhibition attenuates fibrosis in scleroderma (SSc) by modulating the regulatory and effector B cell balance. BAFF inhibition is a potential therapeutic strategy for SSc via alteration of B cell balance. Science Advances, 07/11/2018.

Systemic sclerosis (SSc) with anti-RNA polymerase III positivity following silicone breast implant rupture: possible role of B–cell depletion and implant removal in the treatment. This result may support data suggesting that B-cell depleting therapy may decrease specific autoantibody level in SSc patients, and that these changes are associated with disease improvement. PubMed, Rheumatol Int, 02/03/2017. (Also see Artificial Joints and Silicone Breast Implants)

TIM-1 defines a human regulatory B cell (Bregs) population that is altered in frequency and function in systemic sclerosis (SSc) patients. TIM-1 is a unique marker for the identification of a human IL-10+ Breg subpopulation which is partially superimposed with transitional B cells. Alterations in TIM-1+ B cells could contribute to the development of autoimmune diseases such as SSc. PubMed, Arthritis Res Ther, 2017 Jan 19;19(1):8.

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