The Spectrum of Thyroid Disease in a Community: The Whickham Survey

Tunbridge, W. M. G.; Evered, David; Hall, R.; Appleton, David R.; Brewis, M; Clark, F.; Evans, John Grimley; Young, E. T.; Bird, T.; Smith, Pamela Alethea

doi:10.1111/j.1365-2265.1977.tb01340.x

Cited by 2,210 publications

(1,412 citation statements)

References 33 publications

Supporting

100

Mentioning

1,185

Contrasting

Unclassified

101

Order By: Relevance

“…More recent family studies have shown that up to 50% of the siblings of AITD patients were TAb positive, 8,32 in contrast to a TAb population prevalence of 7-15%. 36 The genetic susceptibility to the production of thyroid antibodies was further supported by several segregation analyses in families with thyroid antibodies that suggested a Mendelian dominant pattern of inheritance. [37][38][39] Indeed, our results have shown CTLA-4 to be linked with TAbs in a dominant inheritance pattern.…”

Section: Discussionmentioning

confidence: 94%

Analysis of the CTLA-4, CD28, and inducible costimulator (ICOS) genes in autoimmune thyroid disease

et al. 2003

View full text Add to dashboard Cite

The cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) gene on 2q33 is associated with autoimmune thyroid diseases (AITDs). Our earlier study in 56 families showed linkage of 2q33 to the presence of thyroid antibodies (TAbs). The goals of this study were to confirm the linkage of the 2q33 region to TAbs, to fine map this region, and study the ICOS gene. We performed a linkage study in an expanded data set of 99 multiplex AITD-TAb families (529 individuals). The highest two-point LOD score of 2.9 was obtained for marker D2S325 on 2q33. To fine map this locus, we genotyped 238 Caucasian AITD patients and 137 controls for five additional markers in the linked locus, which contained the CTLA-4, CD28, and ICOS genes. The A/G singlenucleotide polymorphism at position 49 of CTLA-4 was associated with AITD (P¼0.01, OR¼1.5), while markers inside CD28 and ICOS were not. Functional studies have shown that the G allele was associated with reduced inhibition of T-cell proliferation by CTLA-4. We concluded that: (1) the AITD gene in the 2q33 locus is the CTLA-4 gene and not the CD28 or ICOS genes; and (2) the G allele is associated with decreased function of CTLA-4.

show abstract

Section: Discussionmentioning

confidence: 94%

Analysis of the CTLA-4, CD28, and inducible costimulator (ICOS) genes in autoimmune thyroid disease

et al. 2003

View full text Add to dashboard Cite

show abstract

“…In the Whickham survey (32,33), a population-based study from northeastern England, 2% of the population had a history of either hyperthyroidism or hypothyroidism, compared with 13% of the WGET patients with severe disease (P Ͻ 0.001). In addition, despite the fact that Graves' disease is an unusual disorder in men, 4 (5%) of the 86 men with severe disease in the WGET had a history of Graves' disease before the onset of WG.…”

Section: Discussionmentioning

confidence: 99%

Limited versus severe Wegener's granulomatosis: Baseline data on patients in the Wegener's granulomatosis etanercept trial

Stone¹

2003

Arthritis & Rheumatism

361

153

View full text Add to dashboard Cite

Objective. To report baseline data on 180 patients with Wegener's granulomatosis (WG) enrolled in the WG Etanercept Trial (WGET), and to examine demographic and clinical differences between patients with limited disease and those with severe disease.Methods. Definitions of limited and severe disease were agreed upon by consensus of the investigators at a pretrial meeting and were incorporated into the protocol as a stratification criterion. These data were applied prospectively to the WGET patient cohort, based on clinical features and the intention to treat patients according to disease activity. Data related to disease onset, date of diagnosis, clinical features, antineutrophil cytoplasmic antibody assays, tissue biopsy findings, and other medical history were collected on a baseline medical history form. Physician-investigators from each center participated in the development of this form, and all were certified in its use prior to the start of the trial. Selected data on patients who were screened for the trial but were not enrolled were also collected.Results. Several significant differences between the limited and severe disease subsets were observed. Patients with limited disease were nearly a decade younger at disease onset compared with patients with severe disease. Thirty-three percent of patients with severe disease were women, compared with 58% of those with limited disease. Despite their younger age at symptom onset, patients with limited disease tended to have longer disease duration, a greater likelihood of experiencing exacerbation of previous disease following a period of remission, and a higher prevalence of destructive upper respiratory tract disorders at the time of enrollment (e.g., saddle-nose deformity). Patients with limited WG were less likely than those with severe disease to have antibodies to either proteinase 3 or myeloperoxidase. Patients with severe disease had a higher likelihood of previous thyroid disease, particularly either Graves' disease or Hashimoto thyroiditis, suggesting the possibility of different pathogenetic factors within these disease subsets. Other observed differences between these subsets, such as the greater frequency of alveolar hemorrhage in the severe disease group, were related to the a priori definitions of limited and severe disease.Conclusion. There are significant differences between patients with limited WG and those with severe WG with regard to sex, age, the likelihood of recurrent disease, the risk of damage in certain organ systems, and, possibly, etiologic factors. These differences (and perhaps other differences that are currently unrecognized) in patient subsets may have implications for mechanisms of pathogenesis, prognosis, response to treatment, and the design of future clinical investigations.

show abstract

“…The ability of CTLA-4 to regulate T and B cells has been extensively explored in various human autoimmune diseases, and the results suggest a relevant role in autoimmunity. Originally, an association between CTLA-4 and autoimmune disease was demonstrated in a casecontrol study involving patients with Graves' disease (GD) [15]. Subsequently, the three known polymorphisms of the CTLA-4 gene were investigated for linkage and/or association in a large number of human autoimmune diseases.…”

Section: Autoimmunity and Ctla-4 Geneticsmentioning

confidence: 99%

The soluble CTLA-4 receptor and its role in autoimmune diseases: an update

Saverino

Simone

Bagnasco

et al. 2010

Autoimmun Highlights

View full text Add to dashboard Cite

CTLA-4, initially described as a membranebound molecule, is a costimulatory receptor transducing a potent inhibitory signal. Increasing evidence shows the CTLA-4 gene to be an important susceptibility locus for autoimmune endocrinopathies and other autoimmune disorders. A soluble form of cytotoxic T-lymphocyte-associated antigen-4 (sCTLA-4) has been established and shown to possess CD80/CD86 binding activity and in vitro immunoregulatory functions. sCTLA-4 is generated by alternatively spliced mRNA. Whereas low levels of sCTLA-4 are detected in normal human serum, increased serum levels are observed in several autoimmune diseases (e.g. Graves’ disease, myasthenia gravis, systemic lupus erythematosus, type 1 diabetes, systemic sclerosis, coeliac disease, autoimmune pancreatitis and primary biliary cirrhosis). The biological significance of increased sCTLA-4 serum levels is not fully clarified yet. On the one hand, it can be envisaged that sCTLA-4 specifically inhibits early T-cell activation by blocking the interaction of CD80/CD86 with the costimulatory receptor CD28. On the other hand, higher levels of sCTLA-4 could compete for the binding of the membrane form of CTLA-4 with CD80/CD86 in the later phases of T-lymphocyte activation, causing a reduction in inhibitory signalling. This double-edged nature of sCTLA-4 to block the binding of CD28 to CD80/CD86 may result in different outcomes during the clinical course of an autoimmune disease.

show abstract

The Spectrum of Thyroid Disease in a Community: The Whickham Survey

Cited by 2,210 publications

References 33 publications

Analysis of the CTLA-4, CD28, and inducible costimulator (ICOS) genes in autoimmune thyroid disease

Analysis of the CTLA-4, CD28, and inducible costimulator (ICOS) genes in autoimmune thyroid disease

Limited versus severe Wegener's granulomatosis: Baseline data on patients in the Wegener's granulomatosis etanercept trial

The soluble CTLA-4 receptor and its role in autoimmune diseases: an update

Contact Info

Product

Resources

About