%0 Journal Article %A Nguyen, Bao %A Gopinath, Bamini %A Ma, Gary %A Champion, Bernard %A Wall, Jack %T Cell mediated Immunity Against Three Eye Muscle Antigens and Correlation with Eye Signs in Patients with Transient and Chronic Thyroiditis %B Open Autoimmunity Journal %D 2012 %C Netherlands %I Bentham Open %V 4 %N %P 4-9 %@ 1876-8946 %X %Z FOR Codes: 111301 %0 Journal Article %~ PubMed %A Ardley, Melissa %A McCorquodale, Thomas %A Lahooti, Hooshang %A Champion, Bernard %A Wall, Jack R %T Eye findings and immunological markers in probands and their euthyroid relatives from a single family with multiple cases of thyroid autoimmunity. %B Thyroid Research %D 2012 %C United Kingdom %I BioMed Central Ltd. %V 5 %N 1 %P 4 %@ 1756-6614 %X %Z FOR Codes: 110703 %0 Journal Article %~ PubMed %A McCorquodale, Tom %A Lahooti, Hooshang %A Gopinath, Bamini %A Wall, Jack R %T Long-term follow-up of seven patients with ophthalmopathy not associated with thyroid autoimmunity: heterogeneity of autoimmune ophthalmopathy. %B Clinical Ophthalmology %D 2012 %C United Kingdom %I Dove Medical Press Ltd. %V 2012 %N 6 %P 1063-1071 %@ 1177-5483 %X BACKGROUND: Ophthalmopathy is the most common extrathyroidal manifestation of Graves'' disease. However, in approximately 5% of cases this autoimmune eye disorder occurs in the apparent absence of Graves'' hyperthyroidism: the so-called euthyroid Graves'' disease (EGD). METHODS: Seven patients with EGD were followed for evidence of thyroid and orbital autoimmunity, for up to 10 years. Calsequestrin and collagen XIII antibodies were measured by enzyme linked immunosorbent assay (ELISA), and TSH-receptor (TSH-r) antibodies were measured as TSH-r-binding antibody (TRAb) and thyroid-stimulating immunoglobulin (TSI). Eye signs were characterized and quantified as clinical activity score (CAS), NOSPECS classes, Nunery types 1 and 2, and margin-reflex distance (MRD). RESULTS: Calsequestrin antibodies were detected on at least one occasion in three of the seven patients and collagen XIII antibodies were detected one or more times in five patients. In one patient with isolated congestive ophthalmopathy who was studied intensely, collagen XIII antibodies were initially positive and then became negative as the eye disease stabilized, while antibodies targeting calsequestrin were always negative. TRAb was not detected in any patient, but TSI was detected in three patients on one occasion each. Ultrasound abnormalities were found in four of the six patients for whom this was carried out, but there was no clear evidence for thyroiditis in any of these patients. For comparison, 13 patients were studied with typical Graves'' ophthalmopathy. There were no significant differences compared to EGD in respect to the prevalence of positive calsequestrin or collagen XIII antibodies, but these patients included more smokers (eight out of 13 versus none out of seven). CONCLUSIONS: Earlier studies suggesting that patients with EGD eventually develop thyroid dysfunction have not been confirmed here, although follow-up continues, and the possibility that such patients have had thyroid autoimmunity in the past, or that they will develop it in the future cannot be excluded. Overall, it is likely that the ophthalmopathy associated with Graves'' hyperthyroidism is the same disease as that observed in patients - such as those reported here - in whom thyroid dysfunction and thyroid autoimmunity are not present during the period of follow- up. The role of autoimmunity against the TSH-r in euthyroid patients with ophthalmopathy has not been proven and the significance of the orbital antibodies is unclear. %Z FOR Codes: 110306 111301 %0 Journal Article %~ PubMed %A El-Kaissi, Samer %A Wall, Jack R %T Targeting the thyrotropin receptor in thyroid disease. %B Expert Opinion On Therapeutic Targets %D 2012 %C United Kingdom %I Informa Healthcare %V 16 %N 7 %P 719-727 %@ 1744-7631 %X %Z FOR Codes: 1107 1103 1107 %0 Book Section %A Wall, Jack %A Champion, Bernard %T The Role of Real-Time Thyroid Ultrasonography in the Assessment and Management of Patients with Hashimoto’s Thyroiditis %B Hypothyroidism – Influences and Treatments %D 2012 %C Croatia %I InTech %V %N %P 167-180 %@ 9789535100218 %E Springer, Drahomira %X %Z FOR Codes: 110306 %0 Journal Article %~ PubMed %A De Bellis, Annamaria %A Conzo, Giovanni %A Cennamo, Gilda %A Pane, Elena %A Bellastella, Giuseppe %A Colella, Caterina %A Iacovo, Assunta Dello %A Paglionico, Vanda Amoresano %A Sinisi, Antonio Agostino %A Wall, Jack R %A Bizzarro, Antonio %A Bellastella, Antonio %T Time course of Graves' ophthalmopathy after total thyroidectomy alone or followed by radioiodine therapy: a 2-year longitudinal study. %B Endocrine %D 2012 %C United States %I Humana Press, Inc. %V 41 %N 2 %P 320-326 %@ 1559-0100 %X The findings in hyperthyroid patients with Graves'' orbitopathy (GO) of antibodies against antigens shared between the thyroid and orbit, such as the TSH-receptor (TRAb) and a novel protein G2s (G2sAb), suggested a possible common therapeutic strategy. However, the gold therapeutic standard for hyperthyrodism in these patients remains still unsettled and is mainly based on personal experience. Studies on the effect of total thyroidectomy (TT) alone or followed by radioiodine ablation (RAI) of thyroid remnants showed often conflicting results. This longitudinal study was aimed at evaluating the influence of TT alone or followed by post-surgical RAI with respect to methimazole treatment on the activity and severity of GO in patients with hyperthyroidism and GO. Sixty consecutive patients with Graves'' disease and mild/moderate GO were studied and grouped as follows: group 1, including 25 patients (16F, 9M) undergoing TT alone; group 2, including 10 patients (8F, 2M) undergoing TT followed by RAI for histological evidence of differentiated thyroid cancer; group 3, including 25 patients (18F, 7M) euthyroid under methimazole therapy, studied as controls. Clinical study of ophthalmopathy and measurements of TRAb and G2sAb were performed in all patients at start of the study (time of TT for group 1 and RAI after TT for group 2 and of the first finding of euthyroidism under methimazole treatment for group 3) and after 6, 12, 24 months. Patients of both groups 1 and 2 showed an early significant decrease and a further progressive reduction of the activity and severity of GO with a disappearance of TRAb and a decrease of G2sAb levels during the follow-up, without statistically significant differences between the two groups. Patients in group 3 showed a much later and less marked improvement of GO with persistence of TRAb and G2sAb positivity, even if with reduction of TRAb levels at 12 and 24 months. Our results suggest that in Graves'' patients with large goiter or relapse of hyperthyroidism and mild/moderate GO, TT alone could be an advisable choice to treat hyperthyroidism also improving GO with reduction of cost/benefit ratio. %Z FOR Codes: 111301 %0 Journal Article %A Girgis, Christian %A Champion, Bernard %A Wall, Jack %T Current concepts in Graves' disease %B Therapeutic Advances in Endocrinology and Metabolism %D 2011 %C United Kingdom %I Sage Publications Ltd. %V 2 %N 3 %P 135-144 %@ 2042-0196 %X %Z FOR Codes: 110306 %0 Journal Article %~ PubMed %A Kambo, Jaspreet S %A Girgis, Christian M %A Champion, Bernard L %A Wall, Jack R %T Delayed-Onset Hypoparathyroidism in an Adolescent with Chromosome 22Q11 Deletion Syndrome. %B Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists %D 2011 %C United States %I American Association of Clinical Endocrinologists %V 17 %N 5 %P e123-5 %@ 1934-2403 %X To describe the first case of established chromosome 22q11 deletion syndrome with late onset presentation of hypocalcemia secondary to hypoparathyroidism. %Z FOR Codes: 1103 304 %0 Journal Article %~ PubMed %A Wall, Jack R %A Lahooti, Hooshang %T [Pathogenesis of thyroid eye disease - does autoimmunity against the TSH receptor explain all cases?]. %B Endokrynologia Polska %D 2011 %C Poland %I Wydawnictwo Via Medica %V 162 %N Suppl 1 %P 1-7 %@ 0423-104X %X Thyroid associated ophthalmopathy, or thyroid eye disease (TED), is a complex inflammatory disorder of the eye that, as its name implies, is usually associated with thyroid disease. Clinical observation supports the existence of three main TED subtypes, namely ocular myopathy, congestive myopathy, and mixed congestive and myopathic ophthalmopathy. Although the precise pathophysiology of TED remains unclear, it is likely to reflect an autoimmune reaction involving sensitised T lymphocytes and autoantibodies directed against a specific orbital or thyroid-and-orbital shared antigen(s). One well-studied candidate in this immune reaction is the thyroid-stimulating hormone receptor (TSHR), which is also expressed in the orbital fibroblast and preadipocyte. Most patients with ophthalmopathy have associated Graves'' disease, 10% have Hashimoto''s thyroiditis in which the eye changes are often mild and expressed mainly as upper eyelid retraction (UER), and 10% have no apparent associated thyroid disease - so-called "euthyroid Graves'' disease". Ophthalmopathy can also occur in some patients with transient thyroiditis, thyroid cancer, and Graves'' disease many years after treatment of the hyperthyroidism - situations where TSHR antibodies are not expected to be present, suggesting that the relationship between TSHR antibodies and the eye disorder has not been established for all cases. In our studies of TED we have investigated the nature and significance of antibodies targeting other eye muscle and orbital connective tissue (OCT) antigens, in particular the calcium binding protein calsequestrin (CASQ1) and the orbital fibroblast membrane antigen collagen XIII. Our working hypotheses for the pathogenesis of TED are: i) the initial reaction in the orbit is antibody and T lymphocyte targeting of the TSHR in the OCT compartment, and ii) the associated extra ocular and upper eyelid muscle inflammation reflects either autoimmunity against primary skeletal muscle antigens such as CASQ1 or a secondary, non specific effect of the OCT reactions as proposed by the main proponents of the "TSHR hypothesis". Here, we review the evidence that autoimmunity against the TSHR expressed in the orbit can be implicated in the development of all cases of TED. Although there is a close general correlation between ophthalmopathy and TSHR antibodies there are many exceptions, suggesting that the continued study of the possible role of autoimmunity against calsequestrin and collagen XIII is justified. %Z FOR Codes: 110306 %0 Journal Article %~ PubMed %A El-Kaissi, Samer %A Bowden, Joanne %A Henry, Margaret J %A Yeo, Myra %A Champion, Bernard L %A Brotchie, Peter %A Nicholson, Geoffrey C %A Wall, Jack R %T Association between radioiodine therapy for Graves' hyperthyroidism and thyroid-associated ophthalmopathy. %B International Ophthalmology %D 2010 %C Netherlands %I Springer Netherlands %V 30 %N 4 %P 397-405 %@ 1573-2630 %X To investigate the role of radioactive iodine (RAI) in the onset and progression of thyroid-associated ophthalmopathy (TAO). Forty-six Graves'' disease patients with mild or no ophthalmopathy were prospectively treated with carbimazole (CBZ) (n = 22) or RAI (n = 24). Treatment effects were evaluated clinically over 12 months, and with orbital MRI-measured extra-ocular muscle (EOM) volumes at baseline and at 6 months. The diagnosis of TAO was based on the clinical activity score (CAS) system. There were 11/22 CBZ and 10/24 RAI patients with active ophthalmopathy at baseline. Despite greater mean TSH levels post-RAI (P = 0.003), there was no increase in the likelihood of developing active ophthalmopathy (OR 0.95; 95% CI 0.56-1.61, P = 0.9) or EOM dysfunction (OR 0.52; 95% CI 0.26-1.06, P = 0.074). The increased mean palpebral aperture post-RAI (P = 0.023) and greater mean proptosis in the CBZ group (P = 0.005) were not confirmed when the absolute values of these measurements were examined. There was no association between the treatment received and MRI-measured EOM volumes. In this study, RAI therapy for Graves'' disease did not increase the risk of progression or development of ophthalmopathy in patients with mild or no eye disease at baseline. %Z FOR Codes: 110306 %0 Journal Article %~ PubMed %A de Haan, Sofie %A Lahooti, Hooshang %A Morris, Olivia %A Wall, Jack R %T Epitopes, immunoglobulin classes and immunoglobulin G subclasses of calsequestrin antibodies in patients with thyroid eye disease. %B Autoimmunity %D 2010 %C United Kingdom %I Informa Healthcare %V 43 %N %P 698-703 %@ 1607-842X %X A number of serum autoantibodies are associated with thyroid eye disease (TED), including those reactive against the calcium binding protein calsequestrin (CASQ). There are two isoforms of CASQ namely; CASQ1, found in skeletal, including extra ocular, muscle, and CASQ2, found in cardiac muscle. We determined (i) the reactivity profiles of CASQ1 and CASQ2 antibodies and (ii) the immunoglobulin (Ig) classes and IgG subclasses of CASQ1 antibodies, using enzyme-linked immunosorbent assay. Of the 20 patients with TED tested, 35% were positive for CASQ1 antibodies, 25% for CASQ2 antibodies and two patients (10%) were positive for both antibodies. Of the 12 patients with Hashimoto''s thyroiditis and ophthalmopathy tested, 25% were positive for CASQ1 antibodies, 42% for CASQ2 antibodies and two patients (17%) were positive for both antibodies. CASQ1 antibodies were mainly of the IgG class and IgG1 and IgG3 subclasses. These results suggest that CASQ1 and CASQ2 do not share major epitopes. Because antibodies of the IgG1 and IgG3 subclasses are cytotoxic, CASQ1 antibodies may contribute to the eye muscle damage in patients with TED. Because CASQ1 antibodies were positive in only a third of patients with active TED we are unable to draw conclusions about their role in its pathogenesis. On the other hand, a possible role of CASQ2 antibodies in the aetiology of the cardiac complications of Graves'' disease is a new avenue for research and appears worthy of further investigation. %Z FOR Codes: 110106 110703 110306 %0 Journal Article %~ PubMed %A Tjiang, Hilman %A Lahooti, Hooshang %A McCorquodale, Tom %A Parmar, Kishan R %A Wall, Jack R %T Eye and eyelid abnormalities are common in patients with Hashimoto's thyroiditis. %B Thyroid %D 2010 %C United States %I Mary Ann Liebert, Inc. Publishers %V 20 %N 3 %P 287-290 %@ 1557-9077 %X BACKGROUND: Overt ophthalmopathy is presumed to be uncommon in patients with Hashimoto''s thyroiditis compared to Graves'' disease, where significant eye changes are found in approximately 40% of patients. On the other hand, when observing, more subtle eye changes, particularly upper eyelid retraction (UER) and mild inflammatory signs, may be common in patients with Hashimoto''s thyroiditis. METHODS: We have determined the prevalence and characteristics of eye signs in recently diagnosed patients with Hashimoto''s thyroiditis studied prospectively since 2004 till date in Sydney (Australia). We measured serum orbital antibodies in 20 of the patients in enzyme-linked immunosorbent assay. RESULTS: The overall prevalence of eye signs in patients with Hashimoto''s thyroiditis was 34%, of whom about a quarter had chronic UER, determined as a margin-reflex distance of >5 mm, as the main sign. There was no correlation between eye signs and cigarette smoking. Overall, there was only a modest correlation between eye signs and positive antibody tests, and 40% of patients with no eye signs at the time of study were antibody positive. CONCLUSION: Eye changes, in particular UER, are common in patients with Hashimoto''s thyroiditis. Since thyroid stimulating hormone-receptor antibodies are not usually associated with Hashimoto''s thyroiditis, autoimmune mediated damage of the levator palpebrae superioris (eyelid) muscle cannot be due to these antibodies. Although eyelid abnormalities may be a minor problem for most patients, for some there are major cosmetic implications requiring surgical management. %Z FOR Codes: 110306 111301 110199 %0 Journal Article %~ PubMed %A Gopinath, B %A Wang, J J %A Kifley, A %A Wall, J R %A Eastman, C J %A Leeder, S R %A Mitchell, P %T Five-year incidence and progression of thyroid dysfunction in an older population. %B Internal Medicine Journal %D 2010 %C Australia, United Kingdom, Netherlands, United States %I Wiley-Blackwell Publishing Asia %V 40 %N 9 %P 642-649 %@ 1445-5994 %X Background: Very few studies have assessed both the incidence and progression of thyroid dysfunction in a single older population-based cohort. In this study, we aimed to assess the 5-year incidence, progression and risk factors for development of thyroid dysfunction in an older Australian population. Methods: The Blue Mountains Eye Study is a longitudinal population-based cohort study. During 1997-1999, 1768 participants (???55???years) had thyroid function assessed. After excluding participants reporting any form of treatment for their thyroid condition at baseline, 951 participants (91.4%) without thyroid dysfunction and 54 (5.4%) with thyroid dysfunction were re-examined 5???years later. Thyroid dysfunction was defined using serum thyrotropin (thyroid stimulating hormone (TSH)) screen, followed by serum free T4 assessment. Results: The overall 5-year incidence of thyroid dysfunction was 4.7% (95% confidence interval (CI) 3.4-6.1). Obesity (body mass index ??? 30???kg/m(2) ) and serum TSH > 2???mIU/L at baseline predicted incident overt hypothyroidism (odds ratio (OR) 4.05, CI 1.74-9.41) and (OR 5.46, CI 1.16-25.67) respectively. The 5-year incidence of subclinical hypothyroidism was significantly higher in women than in men, 2.5% versus 0.7% (P= 0.03). Progression to overt hypothyroidism was observed in 17.9% of subjects with subclinical hypothyroidism over 5???years. Conclusions: The 5-year incidence of thyroid dysfunction in this older population was relatively low, and was associated with obesity and serum TSH level > 2???mIU/L at baseline. Over one in six persons with subclinical hypothyroidism progressed to overt thyroid dysfunction over the 5-year period. Our findings highlight the need for appropriate management of subclinical hypothyroidism among older people. %Z FOR Codes: 111706 %0 Journal Article %~ PubMed %A Wall, Jack R %A Lahooti, Hooshang %T Pathogenesis of thyroid eye disease--does autoimmunity against the TSH receptor explain all cases? %B Endokrynologia Polska %D 2010 %C Poland %I Wydawnictwo Via Medica %V 61 %N 2 %P 222-227 %@ 0423-104X %X Thyroid associated ophthalmopathy, or thyroid eye disease (TED), is a complex inflammatory disorder of the eye that, as its name implies, is usually associated with thyroid disease. Clinical observation supports the existence of three main TED subtypes, namely ocular myopathy, congestive myopathy, and mixed congestive and myopathic ophthalmopathy. Although the precise pathophysiology of TED remains unclear, it is likely to reflect an autoimmune reaction involving sensitised T lymphocytes and autoantibodies directed against a specific orbital or thyroid-and-orbital shared antigen(s). One well-studied candidate in this immune reaction is the thyroid-stimulating hormone receptor (TSHR), which is also expressed in the orbital fibroblast and preadipocyte. Most patients with ophthalmopathy have associated Graves'' disease, 10% have Hashimoto''s thyroiditis in which the eye changes are often mild and expressed mainly as upper eyelid retraction (UER), and 10% have no apparent associated thyroid disease - so-called "euthyroid Graves'' disease". Ophthalmopathy can also occur in some patients with transient thyroiditis, thyroid cancer, and Graves'' disease many years after treatment of the hyperthyroidism - situations where TSHR antibodies are not expected to be present, suggesting that the relationship between TSHR antibodies and the eye disorder has not been established for all cases. In our studies of TED we have investigated the nature and significance of antibodies targeting other eye muscle and orbital connective tissue (OCT) antigens, in particular the calcium binding protein calsequestrin (CASQ1) and the orbital fibroblast membrane antigen collagen XIII. Our working hypotheses for the pathogenesis of TED are: i) the initial reaction in the orbit is antibody and T lymphocyte targeting of the TSHR in the OCT compartment, and ii) the associated extra ocular and upper eyelid muscle inflammation reflects either autoimmunity against primary skeletal muscle antigens such as CASQ1 or a secondary, non specific effect of the OCT reactions as proposed by the main proponents of the "TSHR hypothesis". Here, we review the evidence that autoimmunity against the TSHR expressed in the orbit can be implicated in the development of all cases of TED. Although there is a close general correlation between ophthalmopathy and TSHR antibodies there are many exceptions, suggesting that the continued study of the possible role of autoimmunity against calsequestrin and collagen XIII is justified. %Z FOR Codes: 110306 111301 110199 %0 Journal Article %~ PubMed %A Lahooti, Hooshang %A Parmar, Kishan R %A Wall, Jack R %T Pathogenesis of thyroid-associated ophthalmopathy: does autoimmunity against calsequestrin and collagen XIII play a role? %B Clinical Ophthalmology %D 2010 %C United Kingdom %I Dove Medical Press Ltd. %V 4 %N %P 417-425 %@ 1177-5483 %X Thyroid-associated ophthalmopathy (TAO), or thyroid eye disease, is a complex inflammatory disorder of the eye that, as its name implies, is associated with thyroid disease. TAO can be divided into three subtypes: ocular myopathy, congestive myopathy and mixed congestive and myopathic ophthalmopathy. Although the precise pathophysiology of TAO remains unclear it is likely to reflect an autoimmune reaction involving sensitized T-cells and autoantibodies directed against a thyroid and orbital tissue shared antigen. One well studied candidate in this immune reaction is the thyroid-stimulating hormone receptor (TSH-r), expressed in the orbital fibroblast and pre adipocyte. In our studies of TAO, we have investigated the nature and significance of antibodies targeting other eye muscle and orbital connective tissue (OCT) antigens. Our findings suggest that autoimmunity against the eye muscle antigen calsequestrin and the OCT antigen collagen XIII plays a role in the pathogenesis of TAO. We propose that ocular myopathy and chronic eyelid retraction are due to autoimmunity against skeletal muscle calsequestrin in the extraocular and eyelid muscles, respectively. This may be initiated in the thyroid where calsequestrin expression is upregulated, possibly due to a stimulatory effect of TSH-r antibodies. We also propose that congestive ophthalmopathy results from a reaction against the TSH-r or collagen XIII in orbital fibroblast cell membranes. Further insight into the role of eye muscle and OCT antigens in the pathogenesis of TAO may allow for the development of new therapies to treat the eye disorder and reduce patient morbidity. %Z FOR Codes: 110306 111301 110199 %0 Journal Article %~ PubMed %A Nanan, Ralph %A Wall, Jack R %T Remission of Hashimoto's Thyroiditis in a Twelve-Year-Old Girl with Thyroid Changes Documented by Ultrasonography. %B Thyroid %D 2010 %C United States %I Mary Ann Liebert, Inc. Publishers %V 20 %N 10 %P 1187-1190 %@ 1557-9077 %X Background: Although it is known that Hashimoto''s thyroiditis in children and adolescents can go into long-term remission, and that treatment with thyroxine (T4) may not be necessary, it is difficult to quantify changes in the degree of autoimmune destruction of the thyroid. Here we report a patient in whom there was a relationship between functional and anatomical changes as assessed by hormone measurements and ultrasonography. Summary: The patient was a 12-year-old girl with Hashimoto''s thyroiditis who was initially euthyroid and later treated with 50 μg levo-T4 when her free T4 (fT4) had declined from 17 to 7 pmol/L (normal range, 8–22 pmol/L). At this time her thyroid-stimulating hormone (TSH) was 4.1 mIU/L (normal range, 0.30–4.0 mIU/L) and thyroid ultrasonography demonstrated features of early inflammation. Two years later, while on the same dose of T4, ultrasound examination revealed severe end-stage Hashimoto''s thyroiditis and thyroid function tests showed a T4 of 14.0 pmol/L and TSH of 0.81 mIU/L. Twelve months later, however, the thyroid ultrasound had returned to almost normal with only minimal features of inflammation. Thyroid function tests showed a fT4 of 12.8 pmol/L and TSH of 0.75 mIU/L. Her T4 treatment was then stopped. Eight, 17, and 30 weeks after this, her fT4 was 16.8, 9.7, and 13.9 pmol/L, respectively, and her respective TSH values at the same times were 0.10, 2.24, and 0.75 mIU/L. Conclusions: This is the first recording of serial thyroid ultrasound changes in a patient with Hashimoto''s thyroiditis that paralleled changes in thyroid function. This indicates that thyroiditis can go into remission in some children. Thyroid ultrasound may be useful to make presumptive therapeutic decisions in children and adolescents with Hashimoto''s thyroiditis whose dose of thyroid hormone seems to be less than is full replacement. Thyroid function tests, however, should ultimately guide T4 dosage. %Z FOR Codes: 111403 %0 Journal Article %~ PubMed %A Vannucchi, G %A Campi, I %A Bonomi, M %A Covelli, D %A Dazzi, D %A Currò, N %A Simonetta, S %A Bonara, P %A Persani, L %A Guastella, C %A Wall, J %A Beck-Peccoz, P %A Salvi, M %T Rituximab treatment in patients with active Graves' orbitopathy: effects on proinflammatory and humoral immune reactions. %B Clinical and Experimental Immunology %D 2010 %C United Kingdom %I Wiley-Blackwell Publishing Ltd. %V 161 %N 3 %P 436-443 %@ 1365-2249 %X In active Graves'' orbitopathy (GO), proinflammatory cytokines predominate. Circulating thyroid stimulating hormone (TSH)-receptor antibodies (TRAb) have been correlated with GO clinical activity and severity. In preliminary studies rituximab (RTX), an anti-CD 20 monoclonal antibody, has induced clinical improvement of active GO without a change in serum anti-thyroid antibodies. We have studied whether RTX in GO acts by affecting proinflammatory cytokines and thyroid and orbital-directed antibodies. Ten patients with GO were treated with RTX, administered twice intravenously (i.v.) (1000???mg) at days 1 and 15, and 20 with methylprednisolone, administered weekly i.v. (500???mg), for 16 weeks. Patients were studied before treatment, at B cell depletion and at 4, 8, 16, 20, 30 and 50 weeks. Peripheral lymphocytes, serum interleukin (sIL)-6, sIL-6r, chemokine (C-X-C motif) ligand 10 (CXCL10), TRAb and stimulating antibodies (TSAb) and autoantibodies against orbital calsequestrin, collagen XIII and flavoprotein subunit of succinate dehydrogenase (FP-SDH) were measured at baseline and after treatment. Serum IL-6 and sIL-6R concentrations did not change after RTX [P???=???not significant (n.s.)]. Serum CXCL10 increased after RTX at B cell depletion and at 30 weeks (P???