Anna Lucas-Martin

Characterization of neural cell adhesion molecule (NCAM) expression in thyroid follicular cells : induction by cytokines and over-expression in autoimmune glands

NCAM (CD56) is a cell surface glycoprotein of the immunoglobulin superfamily expressed on neuroendocrine and natural killer (NK) cells which has considerable molecular heterogeneity due to differential splicing and post‐translational modifications. NCAM has been detected in the thyroid follicular cells (thyrocytes) immunohistological. We report here the molecular form, the modulation by cytokines and the levels of expression in thyroid pathology. By using a panel of MoAbs to NCAM on Western blots from thyrocyte extract we have determined that these cells express the 140‐ and 180‐kD forms of NCAM, Exposure of primary cultures of thyrocytes to interferon‐gamma (IFN‐Γ), and even more, to the combination of IFN‐Γ plus tumour necrosis factor‐alpha (TNF‐α) induced a clear increase in the expression of NCAM as assessed by FACS analysis. NCAM expression in thyrocytes was assessed by immunofluorescence in 59 surgical specimens of thyroid glands, and was found increased in 11/17 (64%) of Graves’, in 5/25 (20%) of multinodular goitre (MNG) and in occasional adenoma glands. No correlation was found with the expression of HLA class I. class II or the degree of lymphocytic infiltration scored in adjacent sections, but it was often seen in areas infiltrated by macrophages. In conclusion, NCAM is an adhesion molecule whose expression is clearly increased in thyrocytes in autoimmune glands, probably as a consequence of exposure to cytokines locally released. Since one of the forms of NCAM expressed by thyrocytes has the capability to generate intracellular signal it may play a role in normal thyroid function. In addition, NCAM may facilitate the recognition of thyrocytes by lymphocytes, particularly by NK CD56+ lymphocytes.

Regenerating gene Iα is a biomarker for diagnosis and monitoring of celiac disease: a preliminary study

The regenerating gene (REG) is a multigene family in humans that plays a role in tissue regeneration. The REG Iα protein is expressed in the pancreas and the gastrointestinal tract and is involved in the pathophysiology of gastritis, pancreatitis, cancer, inflammatory bowel disease, and type 1 diabetes (T1D). Celiac disease (CD) is an autoimmune disease caused by the ingestion of gluten in genetically susceptible individuals. Our aim was to determine whether the serum REG Iα concentration reflects the destructive/regenerative process in the small bowel in CD. REG Iα was determined by enzyme-linked immunosorbent assay (ELISA) in 40 patients with active CD, and in 19 of them, REG Iα was assessed after following a gluten free diet. As controls, 35 healthy subjects were included in the study. Autoantibodies to transglutaminase, gliadin, and endomisium were measured also. We found a significant increase in REG Iα in the sera of CD patients when compared with controls. REG Iα levels decreased after a gluten-free diet together with a significant reduction in antitransglutaminase antibodies. T1D and pernicious anemia patients displayed normal serum REG Iα concentrations. This preliminary study suggests that REG Iα protein levels can be used as a biomarker for the diagnosis and monitoring of CD.

Treatment of thyroid cancer with the new oral agents

Thyroid malignancies have traditionally been under the care of endocrinologists. Thyroid cancer excellent prognosis, its unresponsiveness to conventional chemotherapy, and the specific and peculiar methods in the follow-up are some of the reasons for its particular management. Thyroid Cancer Guidelines have been published by Endocrine Societies both in the United States [1] and in Europe [2]. Furthermore, the adequate skills and knowledge related to running a good practice differ from the customary oncologic management. In fact, thyroid cancer is generally omitted from the oncology curriculum for oncologists’ residence education, whereas thyroid cancer management comprises a fundamental feature in the instruction of future endocrinologists. As a result, the oncologists’ experience and interest in the management of this particular type of cancer is generally scarce. We have read the position statement by the Spanish Society of Medical Oncology (SEOM) on the treatment of cancer with the new oral agents [3]. We agree with the SEOM members that, for the benefit of our patients, ‘cancer treatment involves the participation of multiple medical specialties’. Our aim is to be collaborative rather than start a controversy. However, we remind that endocrinologists have led the introduction of these new oral drugs in the thyroid cancer treatment scenario [4, 5]. Clinical trials with tyrosine kinase inhibitors (TKI) for thyroid cancer patients have been at the beginning, and currently are, in the hands of endocrinologists [6]. Therefore, we understand that endocrinologists must continue coordinating thyroid cancer patients’ management. Besides that, it is well described that TKI produce a number of endocrine side-effects such as hypothyroidism, which are especially relevant in the follow-up of these patients [5]. As a parallel situation, we know that endocrinologists cannot claim for the exclusive use of any hormone-related drug. We fully understand that glucocorticoids, for instance, need to be widely used by oncologists and other specialists. Therefore, in agreement with the Spanish Society of Radiation Oncologist [7], we consider that the statement of the SEOM has gone beyond the limits of desirable good relationship among different specialists. J. C. Galofre*, J. M. Gomez-Saez, C. A. Escola, E. Anda, A. Calleja, S. Donnay, A. Lucas-Martin, E. Menendez-Torre, V. Pereg, B. Perez-Corral, J. Santamaria, G. Riesco-Eizaguirre & C. Zafon; on behalf of the Thyroid Cancer Committee from the Spanish Society of Endocrinology and Nutrition (SEEN)

One-tube-PCR technique for CCL2, CCL3, CCL4 and CCL5 applied to fine needle aspiration biopsies shows different profiles in autoimmune and non-autoimmune thyroid disorders

Autoimmune thyroid diseases are characterized by lymphocytic infiltration of the thyroid gland. Chemokines are crucial in the recruitment of lymphocytes and might play an important role in the pathogenesis of autoimmune thyroid disease. The aim of this study was to test the feasibility of analysing by one-tube reverse-transcriptase polymerase chain reaction (RT-PCR) technique CC chemokine profiles in samples obtained by fine needle aspiration biopsy (FNAB). In 27 out of 35 (77%) samples, the material was sufficient for analysis and in 16 (59%) chemokines were detected, thus demonstrating the potential of this technique. Moreover, even in this small group, a statistically significant increase of CCL3 and CCL4 was found in samples from patients with autoimmune thyroid disease as compared to those with multinodular goiter. Chemokine profile measured by improved multiamplification techniques in FNAB thyroid samples may become a useful complementary tool for the management of thyroid autoimmune disease as it constitutes a source of data for research of their pathogenesis.

Comments to SEOM clinical guidelines for the treatment of thyroid cancer

Letter to Editor On behalf of the Thyroid Cancer Committee from the Spanish Society of Endocrinology and Nutrition (SEEN).-- et al.

Uso de nuevas moléculas en el tratamiento del cáncer avanzado de tiroides

Juan Carlos Galofréa,∗, José Manuel Gómez-Sáezb, Cristina Álvarez Escolac, Elías Álvarez Garcíad, Emma Anda Apiñanize, Amparo Callejaa, Sergio Donnayf, Anna Lucas-Marting, Edelmiro Menéndez Torreh, Elena Navarro González i, Vicente Peregj, Begoña Pérez Corralk, Javier Santamaría Sandi l, Garcilaso Riesco Eizaguirrec y Carles Zafón Llopism, Toma de posición del Grupo de Trabajo de Cáncer de Tiroides de la Sociedad Española de Endocrinología y Nutrición

A SNP in intron 1 of TSHR controls its thymic expression and susceptibility to Graves’ disease suggesting central tolerance failure in pathogenesis

Graves’ disease (GD) is the paradigm of an anti-receptor autoimmune disease with agonistic auto-antibodies against the thyrotropin receptor (TSHR) being the underlying pathogenic mechanism. TSHR belongs to the category of tissue-restricted antigens (TRAs), which are expressed by medullary thymic epithelial cells (mTECs) and thereby induce central T cell tolerance. In order to understand the association between TSHR gene polymorphisms and GD we tested the hypothesis that TSHR gene variants affect susceptibility to GD by influencing levels of TSHR transcription in the thymus. The results indicate that thymic glands from normal children homozygous for the rs179247 predisposing allele of TSHR had significantly fewer TSHR mRNA transcripts than carriers of the protective allele. In addition, in heterozygous, the TSHR predisposing allele was expressed at a lower level than the protective one as demonstrated by Allele Specific Transcript Quantification. The effect of TSHR SNP rs179247 was thymus-specific and not observed in thyroid glands. These results constitute first evidence for the involvement of central tolerance in the loss of tolerance to TSHR in GD and underscore the concept that variable expression levels of major target autoantigens in the thymus influence the predisposition to autoimmunity presumably by changing the threshold of tolerance.

EditorialUso de nuevas moléculas en el tratamiento del cáncer avanzado de tiroidesUse of new molecules in the treatment of advanced thyroid cancer

Juan Carlos Galofréa,∗, José Manuel Gómez-Sáezb, Cristina Álvarez Escolac, Elías Álvarez Garcíad, Emma Anda Apiñanize, Amparo Callejaa, Sergio Donnayf, Anna Lucas-Marting, Edelmiro Menéndez Torreh, Elena Navarro González i, Vicente Peregj, Begoña Pérez Corralk, Javier Santamaría Sandi l, Garcilaso Riesco Eizaguirrec y Carles Zafón Llopism, Toma de posición del Grupo de Trabajo de Cáncer de Tiroides de la Sociedad Española de Endocrinología y Nutrición