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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

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)

Regulatory T Cells (Tregs) in SLE: Biology and Use in Treatment. We review how Tregs dysfunction in SLE has been manipulated experimentally and preclinically in the attempt to restore, at last in part, the immune disturbances in the disease. PubMed, Curr Rheumatol Rep, 2016 Nov;18(11):67.

Impaired NK–mediated regulation of T-cell activity in multiple sclerosis is reconstituted by IL-2 receptor modulation. Therapeutic immune modulation of IL-2 receptor restores impaired immune regulation in MS by increasing the proportion of CD155-expressing CD4(+) T cells and the cytolytic activity of NK cells. PubMed, Proc Natl Acad Sci U S A, 2016 May 24;113(21):E2973-82. (Also see Multiple Sclerosis and Natural Killer Cells)

Checkpoints for Autoreactive B Cells in Peripheral Blood of Lupus Patients Assessed By Flow Cytometry. This assay will enable studies to identify potential genetic or environmental factors affecting B cell tolerance checkpoints in health and disease and permit monitoring of the B cell response to therapeutic interventions. Wiley Online Library, 04/08/2016.

Intrarenal macrophage infiltration induced by T cells is associated with podocyte injury in lupus nephritis patients. The present study provides possible links between intrarenal T cells, osteopontin, macrophages with reduced podocyte–nephrin and podocytopathy in systemic lupus erythematosus. PubMed, Lupus, 05/04/2016. (Also see Symptoms and Complications of Lupus)

The case for an autoimmune aetiology of type 1 diabetes (T1D). Further data in support of the autoimmune basis of T1D from many fields, including genetics, experimental therapies and immunology, is discussed. PubMed, Clin Exp Immunol. 2016 Jan;183(1):8-15. (Also see Research on Diabetes)

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

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.

The regulatory role of interferon-γ producing gamma delta T cells via the suppression of T helper 17 cell activity in bleomycin–induced pulmonary fibrosis. These results suggested that pulmonary γδT cells seem to play a regulatory role in the development of bleomycin–induced IP mouse model via the suppression of IL-17A production. PubMed, Clin Exp Immunol, 2016 Sep;185(3):348-60.

The role of Dickkopf-1 in joint remodeling and fibrosis A link connecting spondyloarthropathies and scleroderma? Dkk-1 appears to play a crucial role in both joint remodeling/ectopic ossification and fibrosis and may be a prospective therapeutic modality for fibrotic diseases or diseases characterized by pathologic joint remodeling. Seminars in Arthritis and Rheumatism, 08/26/2016.

Frequency of circulating topoisomerase–I–specific CD4 T cells predicts presence and progression of interstitial lung disease (ILD) in scleroderma. Topo–I–specific T cells can be reliably quantified in the peripheral blood of patients with scleroderma, exhibit a pro–inflammatory Th17 phenotype, and predict progression of ILD. BioMed Central, Arthritis Research & Therapy, 05/04/2016. (Also see Pulmonary Fibrosis)

B lymphocytes in systemic sclerosis (SSc): Abnormalities and therapeutic targets. Altered B–cell function may result in tissue fibrosis, as well as autoimmunity and although further studies and greater understanding are needed, B cells are potential therapeutic targets in SSc. Wiley Online Library, 01/04/2016.

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