Microarray profile of B cells from Graves’ disease patients reveals biomarkers of proliferation

Signaling lymphocytic activation molecule (SLAM) and SLAM-associated protein (SAP) play important role in inflammatory and autoimmune diseases. Our study is aimed at detecting the expression of SLAM and SAP in patients with Graves’ disease (GD) and analyzing the effect of SLAM/SAP on circulating blood CD4+CXCR5+Foxp3+ follicular regulatory T (Tfr) cells. The level of SAP in CD4+CXCR5+ T cells and the level of SLAM on CD19+ B cells were significantly increased in the patients with GD, but no significant difference in the level of SLAM on CD4+CXCR5+ T cells was observed between the patients with GD and the healthy controls. A decrease in the percentage of Foxp3+ cells in CD4+CXCR5+ T cells was observed following anti-SLAM treatment, but the percentages of IFN-γ+ cells, IL-4+ cells, and IL-17+ cells showed no obvious differences. The proportion of circulating Tfr cells was decreased in the patients with GD, and the proportion of circulating Tfr cells had a negative correlation with the level of SAP in CD4+CXCR5+ T cells and the levels of autoantibodies in the serum of the patients with GD. Our results suggested that the SLAM/SAP signaling pathway is involved in the decrease of circulating Tfr cells in Graves’ disease.

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Human B Cells Secreting Immunoglobulin G to Glutamic Acid Decarboxylase-65 from a Nondiabetic Patient with Multiple Autoantibodies and Graves’ Disease: A Comparison with Those Present in Type 1 Diabetes1

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.82.8.4171 ◽

1997 ◽

Vol 82 (8) ◽

pp. 2664-2670 ◽

Cited By ~ 2

Author(s):

Jennifer Tremble ◽

Nils G. Morgenthaler ◽

Arjen Vlug ◽

Alvin C. Powers ◽

Michael R. Christie ◽

...

Keyword(s):

B Cells ◽

Glutamic Acid ◽

Immunoglobulin G ◽

Glutamic Acid Decarboxylase ◽

Nondiabetic Patient ◽

Acid Decarboxylase ◽

Graves Disease ◽

Human B Cells ◽

Glutamic Acid Decarboxylase 65

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A Change from Stimulatory to Blocking Antibody Activity in Graves’ Disease during Pregnancy1

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.83.2.4598 ◽

1998 ◽

Vol 83 (2) ◽

pp. 514-518 ◽

Cited By ~ 1

Author(s):

A. W. C. Kung ◽

B. M. Jones

Keyword(s):

B Cells ◽

Absolute Number ◽

Human Thyroid ◽

Graves Disease ◽

Thyroid Cell ◽

Antibody Activity ◽

Inhibitory Antibody ◽

Free T4 ◽

Blocking Antibody ◽

Blocking Antibodies

Remission of Graves’ disease (GD) during pregnancy with recrudescence after delivery is commonly observed. However, as pregnancy is associated with type 2 rather than type 1 cytokine production, a decrease in thyroid-stimulating antibody (TSAb) activity alone is unlikely to account for the remission during pregnancy. We hypothesized that a change in the antibody characteristics may occur as pregnancy advances. Fifteen women were studied in the first, second, and third trimesters of pregnancy and 4 months postpartum. TSH receptor antibodies were determined using human thyroid cell cultures, and lymphocyte subsets were measured by flow cytometry. Median TSAb (determined by cAMP release) decreased from 280% (96–3200) to 130% (range, 35–350; P < 0.05) during pregnancy, but no significant change was noted with the TSH binding inhibitory antibody (TBII; determined by RRA). Thyroid stimulation-blocking antibody (TSBAb; inhibition of TSH-stimulated cAMP release) increased from 16 ± 9% to 43 ± 16% (mean ± sd; P < 0.005). The increase in TSBAb was observed even among those patients who were in clinical remission before pregnancy. Overall, a negative correlation was observed between TSBAb activities and free T4 levels during pregnancy (r = −0.279; P < 0.05). Reciprocal changes in TSAb, TBII, and TSBAb levels were observed in the seven patients who relapsed during the postpartum period. In comparison, the healthy pregnant women (n = 14) were all negative for TSAb, TBII, and TSBAb throughout pregnancy. The absolute number of T lymphocytes, T helper cells, and natural killer cells, but not B cells, decreased significantly during pregnancy in both healthy women and GD patients. GD patients had significantly more CD5+ B cells at all stages of pregnancy compared to controls. In conclusion, a change in specificity from stimulatory to blocking antibodies was observed in GD patients during pregnancy and may contribute to the remission of GD during pregnancy.

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Characterization of Regulatory B Cells in Graves’ Disease and Hashimoto’s Thyroiditis

PLoS ONE ◽

10.1371/journal.pone.0127949 ◽

2015 ◽

Vol 10 (5) ◽

pp. e0127949 ◽

Cited By ~ 26

Author(s):

Birte Kristensen ◽

Laszlo Hegedüs ◽

Steven K. Lundy ◽

Marie K. Brimnes ◽

Terry J. Smith ◽

...

Keyword(s):

B Cells ◽

Hashimoto’S Thyroiditis ◽

Hashimoto's Thyroiditis ◽

Graves Disease ◽

Regulatory B Cells

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Thyrotrophin receptor-specific memory T cell responses require normal B cells in a murine model of Graves’ disease

Clinical & Experimental Immunology ◽

10.1111/j.1365-2249.2003.02322.x ◽

2003 ◽

Vol 134 (3) ◽

pp. 396-402 ◽

Cited By ~ 11

Author(s):

P. PICHURIN ◽

H. ALIESKY ◽

C-R. CHEN ◽

Y. NAGAYAMA ◽

B. RAPOPORT ◽

...

Keyword(s):

T Cell ◽

B Cells ◽

Murine Model ◽

T Cell Responses ◽

Graves Disease ◽

Memory T Cell ◽

Cell Responses ◽

Specific Memory

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Cold reactive lymphocytotoxic activity in autoimmune thyroid disease

Acta Endocrinologica ◽

10.1530/acta.0.1090492 ◽

1985 ◽

Vol 109 (4) ◽

pp. 492-498 ◽

Cited By ~ 1

Author(s):

Marilyn Ryan ◽

Vitaya Sridama ◽

Leslie J. DeGroot

Keyword(s):

Monoclonal Antibodies ◽

T Cell ◽

B Cells ◽

Thyroid Disease ◽

Autoimmune Thyroid Disease ◽

T Cell Subsets ◽

Graves Disease ◽

Positive Correlation ◽

Autoimmune Thyroid ◽

Normal Controls

Abstract. An increased incidence of cold-reactive lymphocytotoxic activity (LCTA) has been demonstrated in the sera of patients with autoimmune thyroid disease. Twenty-six of 79 (33%) patients with Graves' disease and 9 of 21(43%) patients with Hashimoto's thyroiditis had cold-reactive LCTA detected by microcytotoxicity assay compared to 6 of 42 (14%) normal controls. There was no correlation between LCTA and age, sex, MCHA titre or TGHA titre. A positive correlation with FTI and LCTA in Hashimoto's patients was demonstrated, but no such correlation was demonstrable in Graves' patients. The lymphocytotoxic activity was directed preferentially against B cells. There was no preferential lysis of T-cell subsets as defined by monoclonal antibodies, and the lymphocytotoxins were equally reactive with normal lymphocytes and toxic Graves' lymphocytes. The significance of cold-reactive lymphocytotoxic activity in the pathogenesis of autoimmune thyroid disease remains to be determined.

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