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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.

B Cells and T Cells and Autoimmunity

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)

Disturbed T Cell Signaling and Altered Th17 and Regulatory T Cell Subsets in the Pathogenesis of Systemic Lupus Erythematosus. In patients with SLE increased numbers of autoreactive Th17 cells have been documented, and Th17 cells appear to be responsible for tissue inflammation and damage. PubMed, Front Immunol, 2015 Nov 30;6:610.

Renal involvement in primary Sjögren's syndrome (SS). The prevalence of renal SS, its presentation, likely pathogenesis and treatment is reviewed in this article. PubMed, Rheumatology (Oxford), 2015 Sep;54(9):1541-8. (Also see Sjögren's Syndrome)

Update on the immunobiology of Sjögren's (pSS) syndrome. Progress made during the last few years on the pathogenesis of pSS has been mirrored by clinical trials directed at inhibiting cytokines, B, or T cell responses. PubMed, Current Opinion in Rheumatology, 08/04/2015. (Also see Sjögren's Syndrome Research)

Treatment with belimumab restores B cell subsets and their expression of B cell activating factor (BAFF) receptor in patients with primary Sjogren's syndrome (pSS). Targeting BAFF with belimumab is successful in normalizing B cell frequency, phenotype and functions in pSS. PubMed, Rheumatology (Oxford), 03/03/2015. (Also see Treatments for Symptoms of Sjogren's Syndrome)

Memory B cell subsets and plasmablasts are lower in early than in long-standing Rheumatoid Arthritis. The onset of RA is characterized by higher percentages and absolute numbers of naïve B cells and could represent a promising biomarker of outcome. PubMed, BMC Immunol, 2014 Sep 4;15(1):28. (Also see Rheumatoid Arthritis)

Implication of Epstein-Barr virus (EBV) infection in disease-specific autoreactive B cell activation in ectopic lymphoid structures of Sjogren's syndrome (SS). Active EBV infection is selectively associated with ectopic lymphoid structures in salivary glands of Sjogren's syndrome and appears to contribute to local growth and differentiation of disease-specific autoreactive B-cells. PubMed, Arthritis Rheumatol, 2014 May 28. (Also see Sjogren's Syndrome)

Autoimmune Aspects of Type 2 Diabetes Mellitus (T2DM) — A Mini–Review. The review focuses on autoimmune involvement in T2DM, with an emphasis on latent autoimmune diabetes of the adult, the humoral immune response and specifically the role of B and T cells as links between inflammatory and autoimmune reactions. Gerontology 2014;60:189-196. (Also see Diabetes)

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

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 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)

Connective tissue diseases: Nucleosomes and systemic sclerosis (SSc). New observations suggest that nucleosomes can mediate both IgG production and B–cell proliferation, via Toll–like receptor signalling, and thereby affect the pathogenesis of SSc. Nature Reviews Rheumatology, 02/04/2016.

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.

Systemic sclerosis: New evidence re-enforces the role of B cells. Recent evidence suggests that B cells are also likely to contribute in the pathogenesis of the disease. PubMed, Autoimmun Rev, 10/21/2015.

Reduced type I collagen gene expression by skin fibroblasts of patients with systemic sclerosis after one treatment course with rituximab. These data provide further evidence of B-cell involvement in the pathogenesis of scleroderma and targeting B cells may be a promising treatment for scleroderma patients. PubMed, Clin Exp Rheumatol, 2015 Sep-Oct;33 Suppl 91(4):160-167. (Also see Clinical Trials)

Rituximab in diffuse cutaneous systemic sclerosis (SSc): should we be using it today? We summarize the therapeutic use of rituximab in SSc and the basic science evidence suggesting that B cells and autoantibodies are the primary drivers of fibrosis in skin and lung tissue. PubMed, Rheumatology (Oxford), 07/01/2015. (Also see Scleroderma Clinical Trials)

Involvement of CD161+ Vδ1+ yδ T cells in systemic sclerosis (SSc): association with interstitial pneumonia (IP). The small proportion and the altered cell functions of CD161+ Vδ1+ yδ T cells among peripheral blood mononuclear cells in SSc patients play a role in the pathogenesis of IP and may play a regulatory role in pathogenesis. PubMed, Rheumatology (Oxford), 2014 Jun 27.

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