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Amino acid sequence of a tryptic peptide of human thyroglobulin reactive with sera of patients with thyroid diseases.

Autoantibodies to human thyroglobulin (hTg) are found in the sera of many patients with thyroid diseases. To localize epitopes recognized by these autoantibodies, hTg was incubated with tryspin for 4 hours at 37 degrees C under non-reducing conditions. Releasing peptides from hTg in their natural conformation. These peptides were then analyzed by western immunoblot using either autoantibodies from patients with autoimmune thyroiditis or murine monoclonal antibodies (mAb) produced against hTg. The autoantibodies reacted primarily with two low molecular weight peptides with apparent molecular weights (MWap) of 15 and 20 kDa. The pattern of tryptic peptides recognized by these autoantibodies resembled that of one of the mAbs (137C1), as shown by immunoblots in either one or two dimensional SDS-PAGE. To characterize these peptides further, they were separated by a high performance liquid chromatography (HPLC). The column separated the 4-hour tryptic digest of hTg into multiple peptide peaks. Further analysis by SDS-PAGE showed that one of these peaks contained the 15 kDa peptide. The 15 amino acid sequence at the amino-terminus of this peptide was determined. This amino acid sequence (KVPTFATPWPDFVPR) corresponds to a unique sequence near the carboxyl-terminal end of hTg, starting with amino acid 2657. The size of the peptide indicates that it extends to the carboxyl-terminal end of hTg. This fragment contains one of the antigenic sites of hTg that binds autoantibodies from patients with autoimmune thyroid disease.

Amino Acid Sequence↗

Thyroid disease in a psychogeriatric population.

Over a six-year period, routine biochemical screening for thyroid disease was carried out on 662 patients aged 65 years and older, admitted to the psychogeriatric unit of a major psychiatric hospital. Hypothyroid values were found in 1.2% of the population (8 patients). Hyperthyroid values occurred in 0.76% (5 patients). The thyroid abnormality was considered a significant factor in the psychiatric presentation of only two patients and in both the thyroid disease was clinically apparent. Practical benefits obtained were so disappointing that they did not justify the practice of routine screening in this type of patient.

Age Factors↗

Measurement of serum PDN-21 (Katacalcin) levels by radioimmunoassay in patients with various thyroid diseases.

We established a radioimmunoassay (RIA) using anti-PDN-21 antiserum, which was obtained by immunizing rabbits with synthesized PDN-21, and the basic results are described in this report, with discussion of the significance of PDN-21 determination in various thyroid diseases. In this RIA, the double antibody technique was used for B/F separation. This assay yielded excellent standard curves, specificity, recovery and reproducibility showing that the assay is satisfactory from the clinical standpoint. The upper limit of the normal PDN-21 level was 67 pg/ml in 98 healthy persons. Only patients with medullary carcinoma of the thyroid among patients with various thyroid diseases showed specifically positive assay results. The level was 110 to 18,300 pg/ml (mean, 5,940 pg/ml) in 7 patients whose levels were determined preoperatively, and 64 to 140,000 pg/ml (mean, 10,900 pg/ml) in 18 patients whose levels were determined postoperatively. Thus, PDN-21 levels increased very sharply in the settings of recurrence and tumor residue. These results suggest that PDN-21 has the potential to be an extremely sensitive, highly specific marker for medullary carcinoma of the thyroid.

Adenocarcinoma, Follicular↗

Blood coagulation, fibrinolytic activity and lipid profile in subclinical thyroid disease: subclinical hyperthyroidism increases plasma factor X activity.

BACKGROUND AND OBJECTIVES: Various abnormalities of coagulation and fibrinolysis occur in patients with thyroid diseases, and may range from subclinical laboratory abnormalities to clinically significant disorders of coagulation and, rarely, major haemorrhage or thromboembolism. The influence of subclinical hypothyroidism (SHypo) on haemostasis is controversial, both hypercoagulable and hypocoagulable states have been reported. A hypercoagulable state might be a risk factor for thromboembolic disease in SHypo. On the other hand, subclinical hyperthyroidism (SCHyper) is associated with enhanced cardiovascular risk. In the English literature, there are no studies on changes in coagulation and fibriolytic status in subjects with SCHyper. Therefore, the aim of the present study was to investigate the markers of endogenous coagulation and fibrinolysis, and to evaluate the relationships between serum lipid profile and thyroid hormones and these haemostatic parameters in subclinical thyroid patients. DESIGN AND METHODS: Various haemostatic parameters were investigated in 30 patients with SHypo and 20 patients with SCHyper and compared to 20 euthyroid controls. Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, factors V, VII, VIII, IX and X activities, vWF, antithrombin III (AT III), protein C, protein S, tissue plasminogen activator (t-PA) and tissue plasminogen activator inhibitor-1 (PAI-1), as well as common lipid variables, were measured. The relationships between serum thyroid hormones and these haemostatic parameters were examined. RESULTS: Compared with the control subjects, only FX activity was significantly increased in patients with SCHyper (P < 0.01). Total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels were significantly higher in patients with SHypo compared with the control group (P < 0.001 and P < 0.01, respectively). TC levels were significantly higher in patients with SCHyper than in controls (P < 0.05). No differences could be found in coagulation/fibrinolysis parameters between subclinical hypothyroid patients and control subjects. In patients with SCHyper, serum TSH level was positively correlated with FX activity (r: 0.58, P < 0.01) and inversely correlated with PAI-1 (r: -0.55. P < 0.05). Serum TG levels were inversely correlated with plasma activities of factors V, VII, VIII, IX, X and vWF (r: -0.83, P < 0.001; r: -0.68, P < 0.05; r: -0.61, P < 0.05; r: -0.77, P < 0.01; r: -0.63, P < 0.05; r: -0.60, P < 0.05, respectively). Serum TC levels were positively correlated with plasma fibrinogen levels (r: 0.72, P < 0.05). Serum HDL-C levels were positively correlated with protein S activity (r: 0.68, P < 0.05) and negatively correlated with F VII activity (r: -0.69, P < 0.05). Also, in patients with SHypo, serum TG levels were positively correlated with serum TSH levels (r: 0.42, P < 0.05), plasma activities of factors V, VII and X (r: 0.42, P < 0.05; r: 0.54, P < 0.01; r: 0.57, P < 0.01, respectively) and negatively correlated with plasma fibrinogen levels (r: -0.41, P < 0.05). Serum TC levels were positively correlated with factors V and X (r: 0.42, P < 0.05; r: 0.58, P < 0.01, respectively) and negatively correlated with t-PA Ag levels (r: -0.44, P < 0.05). Serum HDL-C levels were inversely correlated with F VII activity (r: -0.48, P < 0.05). INTERPRETATION AND CONCLUSIONS: Some differences were found in the haemostatic parameters and lipid profile between the subclinical thyroid patients and healthy controls. Increased factor X activity in patients with subclinical hyperthyroidism represent a potential hypercoagulable state, which might augment the already existing risk for atheroscleroic complications. Also, subclinical hypothyroid patients exhibit a more atherogenic lipid profile compared with healthy individuals. Therefore, subclinical hypothyroidism is also associated with an increased risk of cardiovascular disease. However, thyroid hormones may play a role at different levels of the complex haemostatic system in subclinical thyroid disease.

Adult↗

Tracking of indium-111-oxine labelled lymphocytes in autoimmune thyroid disease.

Peripheral lymphocytes (approximately 10(8)) from 4 subjects affected by autoimmune thyroid disease (2 Hashimoto's thyroiditis, 1 primary myxoedema, 1 Graves' disease) and 4 normal subjects were labelled in vitro with 40 microCi of indium-111-oxine and, following autologous injection, the distribution of the cells in the body was investigated by gamma camera imaging. Lymphocytes in the thyroid were observed 24 h after injection in both patients with Hashimoto's thyroiditis and in the patient with primary myxoedema, but not in the patient with Graves' disease or in any of the controls. To our knowledge, this is the first report using this method to try and demonstrate lymphocytes in the thyroid gland, and supports the concept that cell-mediated immunity may be playing an important role in the pathogenesis of Hashimoto's thyroiditis and primary myxoedema.

Adult↗

Characteristics of autoimmune thyroid disease occurring as a late complication of immune reconstitution in patients with advanced human immunodeficiency virus (HIV) disease.

Experimental evidence from animal models has provided a framework for our current understanding of autoimmune disease pathogenesis and supports the importance of genetic predisposition, molecular mimicry, and immune dysregulation. However, only recently has evidence emerged to support the role of immune dysregulation in human organ-specific autoimmune disease. In the current study of the "late" manifestation of autoimmune thyroid disease (AITD) in a cohort of human immunodeficiency virus (HIV)-positive patients following highly active antiretroviral therapy (HAART), we discuss how immune dysregulation and factors associated with the immunopathology of HIV infection fit the current understanding of autoimmunity and provide a plausible basis for our clinical observations. De novo diagnoses of thyroid disease were identified between 1996 and 2002 in 7 HIV treatment centers (5/7 centers completed the study). Patients were diagnosed as clinical case entities and not discovered through thyroid function test screening. Paired plasma specimens were used to demonstrate sequential rise in thyroid antibodies. Seventeen patients were diagnosed with AITD (median age, 38 yr; 65% were of black African or black Caribbean ethnicity; and 82% were female). The median duration of immune reconstitution was 17 months. Graves disease (GD) was diagnosed in 15 of 17 patients. One patient developed hashithyrotoxicosis with atypically raised C-reactive protein, and another developed hypothyroidism. One GD patient had associated secondary hypoadrenalism. The estimated combined prevalence of GD for 4 treatment centers for female patients was 7/234 and for males was 2/1289. The denominator numbers were matched controls, from 4 centers able to provide data, who commenced HAART during the same time (January 1996 to July 2002) and who did not develop clinical AITD. The mean baseline pre-HAART CD4 count was 67 cells/mL, and the mean increase from nadir to AITD presentation was 355 cells/mL. AITD patients were more likely than controls (95% confidence interval, chi-square test) to be severely compromised at baseline (as defined by a CD4 count < 200 cells/mL or the presence of an acquired immunodeficiency syndrome [AIDS]-defining diagnosis), and to experience greater CD4 increments following HAART. AITD may be a late manifestation of immune reconstitution in HIV-positive patients taking HAART, and immune dysregulation may be an important factor.

Adult↗

[Estimation of anti-thyroid peroxidase autoantibody (TPOAb) and anti-thyroglobulin autoantibody (TgAb) in patients with various thyroid disease--comparison between histopathological findings and serological results in patients with Hashimoto's thyroiditis].

We compared and evaluated titers of AMC (anti-microsome antibody), and ATG (anti-thyroglobulin antibody) by passive gelatin-agglutination and by radioimmunoassay in 170 sera from 129 patients with various thyroid diseases and 41 normal subjects. The results of conventional ATG and TgAb by RIA correlated (r = 0.731) and those of conventional AMC and TPOAb correlated well (r = 0.907), with discrepancies mostly limited to sera with low antibody titers. Five patients with Hashimoto's thyroiditis showed positive results in AMC, whilst negative in TPOAb. These sera had positive ATG autoantibody and preincubation with thyroglobulin inhibited the agglutination reaction of AMC tests, suggesting ATG producing false positive results in AMC assay. The prevalences of positive TgAb rates were higher than (p < 0.001) ATG in patients with Hashimoto's disease (96.6% vs 50.0%) and Graves' disease (76.9% vs 46.1%). However, the prevalences of positive TPOAb were not different from AMC (Hashimoto's disease 75.9% vs 81.0%: Graves' disease 80.8% vs 76.9%). In patients with Hashimoto's thyroiditis, our study demonstrates the results of TgAb by RIA reflects the pathological findings and the diagnostic sensitivity increases by using in combination with TPOAb.

Adult↗

Rheumatoid arthritis in thyroid disease positive and negative same-sexed sibships.

A total of 249 rheumatoid arthritis (RA) same-sexed sibships were clinically documented, HLA-typed and had auto-antibody screens performed. Sibships with a history of thyroid disease (TD) or significant thyroid antibodies were categorized as 'thyroid' sibships and the rest 'non-thyroid'. TD was more common in the female RA sibships than controls, particularly in the RA probands. The presence of thyroid microsomal antibody, but not thyroglobulin antibody, was significantly higher in all members of the female sibships, and in the probands and non-RA siblings of the male sibships. Comparing the thyroid and non-thyroid sibships, there was no significant difference in the distribution of HLA haplotypes in RA-RA sibling pairs, and HLA-DR status, clinical or immunological characteristics of the probands. These data do not support the concept that predisposition to RA in thyroid sibships might be non-DR4 or non-HLA linked.

Arthritis, Rheumatoid↗

[Functional results of surgical treatment of thyroid diseases in children and adolescents].

Under investigation were functional results of the surgical treatment of different diseases of the thyroid gland in children and juveniles. The assessment of the physical, sexual, psychoemotional development was made in remote terms (from 1 to 15 years). High rate of malignization of the nodular goiter requires choice of the optimal time for surgery in cases with adenomatous goiter, the development of hypothyrosis in patients with low functional activity of the thyroid adenoma making early operations necessary independent of the age.

Adolescent↗

[Diagnosis of thyroid diseases using imaging procedures with reference to nuclear magnetic resonance tomography].

Results of MR imaging performed in 74 patients with diseases of the thyroid gland and in normal persons are compared with nuclear medicine (99mTc 04 and 131J scans) and sonography (5 and 7.5 MHz transducers, linear scans) results. The MR-signal intensity of hot nodules--Plummers' disease--is not specific. Therefore scintigraphy combined with sonography remain the methods of choice for the diagnosis of hyperfunctioning nodules. Morphologic alterations within the thyroid gland are detected by MRT as well as by ultrasound. But when lesions are not limited to the thyroid bed MRT will become the imaging examination of choice. Therefore MRT can be useful for scanning retrotracheal and superior mediastinal extent of thyroid lesions. Also clinically inapparent metastases to the cervical and mediastinal nodes may be detected.

Adenoma↗

Bacterial virulence antigens and the pathogenesis of autoimmune thyroid diseases (AITD).

There is now substantial evidence that autoimmune thyroid diseases (AITD) coincide with a subclinical persisting infection with Yersinia enterocolitica (YE) which manifests through humoral and cellular immune reactions against YE at the onset of AITD. The humoral and cellular crossreactivities of YE with thyroid autoantigens are exclusively directed against conformational epitopes of YE membrane associated antigens and of YE plasmid encoded virulence proteins (YOPs). Especially, the outer membrane domain of the TSH-Receptor (THSR) appears to have conformational homologies with YE antigens. Immunological- and molecular findings, however, do not allow definite conclusions about a potential role of YE-infection in AITD, although the evidence is suggestive. Recent investigations on the effect of YE-superantigen (Sag) on T-cells from patients with AITD as well as AITD like manifestations in YE immunized mice and rats may yield more conclusive information about the role of YE infection in the pathogenesis of AITD.

Animals↗

Cold reactive lymphocytotoxic activity in autoimmune thyroid disease.

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.

Adolescent↗

[Assessment of the influence of the Chernobyl nuclear disaster on incidence of thyroid diseases among children in Poland. Preliminary results].

It was attempted to assess the incidence of thyroid diseases in Polish children born between 1980-1986, who at the time of the Chernobyl nuclear disaster were 0-6 years old, or whose mothers were in the third trimester of pregnancy. 3071 children have been examined, 1772 girls and 1299 boys. The following were assessed in each child: the health status, the developmental level, the thyroid ultrasound examination, and the level of TSH, FT4, antithyroid antibodies ATM and ATGL in the blood serum. Disorders in thyroid morphology (abnormal echogenicity) have been found in 462 children (15%), almost twice as much in girls than in boys. Goiter has been recognized in 4.6% of all children, an abnormal echogenity in 5.4% and focal changes in 4.8%. 3.9% of children have been found to have a high level of ATM antibodies, and 8.7%--a high level of ATGL antibodies. Among 6 children, who had thyroidectomy, 2 children have been diagnosed to have ca papillary and 4 children--adenoma.

Accidents↗

Prevalence of HCV antibodies in autoimmune thyroid disease.

BACKGROUND AND OBJECTIVES: Auto-immune thyroid disease (AITD) has often been reported during interferon-alpha therapy for chronic viral C hepatitis (HCV) or other diseases. Recently, a high AITD prevalence has been reported in HCV independently on alpha-interferon therapy. The aim of our study is to investigate the possible relationship between AITD and HCV and HBV virus infections, and their influence on the thyroid function. MATERIAL AND METHODS: We prospectively studied 112 patients with AITD (94 women and 18 men; mean age: 49.8 +/- 14.9 yrs) and 88 patients with non-toxic goitre (NTG) (73 women and 15 men; mean age: 50.2 +/- 13.5 yrs) as controls. In all patients HCV antibodies, HBsAg and anti-HBs antibodies, TSH, FT3 and FT4 serum levels, circulating anti-thyroid-peroxidase antibodies (TPO-Ab) and anti-thyroglobulin antibodies (TG-Ab) were measured. RESULTS: HCV antibodies were positive in 11.6% of AITD patients (13/112) and in 2.3% of controls (2/88) (P < 0.05), the prevalence of HCV in the controls being similar to the expected value in the general population (about 2%). HBsAg and anti-HBs were found only in 2.6% of AITD patients (3/112) and 1.1% of controls (1/88) (P = NS), according to the expected value in the general population (about 2.5%). No difference in thyroid function was observed between positive and negative HCV subgroups. CONCLUSION: A significant association between HCV infection and AITD was found. This finding confirms that HCV, but not HBV, could be one of the environmental factors responsible for the breakdown of immunological tolerance. Therefore detection of TPO-Ab and TG-Ab in all HCV patients, independently of IFN therapy, is suggested and the utility of a screening for HCV in all AITD patients is stressed.

Adult↗

Antigen presentation in human autoimmune thyroid disease.

Monocyte/macrophage function in patients with autoimmune thyroiditis was investigated by their presentation of two distinct antigens; sheep red blood cells (SRBC) and human thyroglobulin (hTg) using in vitro systems designed for antibody induction. Purified peripheral blood monocyte/macrophages were primed by prefeeding with antigen for 60 min at 37 degrees C, washed, and co-cultured with autologous lymphocytes under a variety of incubation conditions. The most successful system employed 5% monocyte/macrophages with autologous T-B cells in the presence of the mitogen Staphylococcus aureus and B-cell differentiating factors. Under such conditions the anti-SRBC plaque-forming cell (PFC) response was amplified equally (approximately 10-fold) by SRBC-fed monocyte/macrophages in normal controls and patients with autoimmune thyroiditis rendered euthyroid with thyroxine replacement. hTg-fed monocyte/macrophages induced a 4-fold increase in anti-hTg PFC in selected patients with autoimmune thyroiditis examined under similar conditions (mean 36 +/- 3 PFC per 10(6) T-B cells). These data indicated that antigen processing by monocyte/macrophages was normal in patients with autoimmune thyroid disease.

Adult↗

Contribution of fine needle aspiration cytology to diagnosis and management of thyroid disease.

AIMS: To determine the role of fine needle aspiration cytology (FNAC) in the diagnosis and management of thyroid disease. METHODS: Clinical histories of 144 patients who had undergone FNAC of the thyroid were analysed. Clinical presentation, non-invasive investigations including hormone assays, ultrasound, and isotope scan procedures were compared with FNAC diagnoses in all cases and with histological diagnosis in the 28 cases (19%) that had undergone surgery. Clinical management was decided upon combining all of the above investigations. The relative contribution of the FNAC was divided into: essential, additional and non-contributory, misleading. RESULTS: FNAC diagnoses included: 29 (16%) benign colloid goitre, 56 (39%) benign cystic goitre, 24 (17%) thyroiditis, and 22 (15%) neoplasms. Nineteen (13%) of the specimens were unsatisfactory. When compared with clinical diagnoses based on non-invasive diagnostic investigations FNAC represented no improvement on the diagnosis of benign colloid/cystic goitre (55% v 54% respectively). It represented an improvement on the diagnosis of thyroiditis (9% v 17% respectively). FNAC decreased clinically suspicious lesions in which 22 neoplasms were diagnosed from 37% to 15%. Eleven patients with neoplasms underwent surgery and neoplasms were confirmed histologically. Others including lymphoma, metastatic carcinoma, and analplastic carcinoma were managed conservatively. There were four false negative FNAC diagnoses (3%) in clinically suspicious lesions, found on histology to be benign follicular adenomas. CONCLUSIONS: FNAC had an essential role in the diagnosis and management of 23% of our patients, a confirmatory role in 61% of patients, a non-contributory role in 13% when specimens were inadequate, and was misleading in 3% where results were false negative. The positive identification of thyroiditis and neoplasia stands on its own as a justification for FNAC.

Adolescent↗

[Clinical nuclear medicine in thyroid diseases].

Both in vivo and in vitro isotopic tests are available for the diagnosis of thyroid diseases. As in vitro tests, serum concentrations of T4, T3, free T4, free T3, TSH, TBG, and thyroglobulin (Tg) are determined by RIA or by IRMA. TSH receptor antibodies are measured by RRA for TSH. In order to differentiate blocking from stimulating antibodies, however, assessment of biological activity of the antibody by another type of method such as TSAb assay is required. Radioassays for anti-Tg and anti-TPO antibodies have recently been developed. The former assay is sensitive enough to make early diagnosis of Hashimoto's thyroiditis. The serum Tg measurement by a newly developed IRMA is applicable even in cases with anti-Tg antibodies. Radiolabeled T4-analogs are most frequently used in the RIA of free T4. A one-step labeled antibody method (Amerlex MAB kit) and a sensitive RIA with use of equilibrium dialysis (Model FT4 kit) have recently been in clinical application in our country. These two assays have an advantage of overcoming two major problems, effects of albumin and anti-T4 antibodies, that the analog method has. As in vivo isotopic tests, thyroid scintigraphy using 123I or 99mTc with the combined assessment of the thyroidal uptake rate of each radionuclide and tumor imaging are performed. The thyroid scintigraphy gives functional information, being useful for the differential diagnosis of destructive thyrotoxicosis from Graves' hyperthyroidism. Hypothyroid patients with increased 123I or 99mTc uptake are suspected highly to have dyshormonogenesis or reversible hypothyroidism due to iodine excess.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Autoimmune thyroid disease susceptibility loci in a large Chinese family.

OBJECTIVES: The autoimmune thyroid diseases (AITDs) comprising Graves' disease (GD) and Hashimoto's thyroiditis (HT) are complex genetic diseases, which result from an interaction between predisposing genes and environmental triggers. The aim of our study was to dissect the genetic predisposition to GD and HT in one large Chinese family with multiple members affected with AITD. PATIENTS: We completed a whole genome screen of a large multiplex Chinese-American family. We enrolled 27 family members from three generations. Eight members were affected with AITD, six had GD and two had HT. DESIGN: We determined the information limits of the family. Power calculations indicated that the maximum attainable LOD scores were 5.1 assuming dominant inheritance, and 3.4 assuming recessive inheritance. These estimates both assumed 100% penetrance and one gene. Whole genome screening was performed using 400 highly polymorphic and densely spaced microsatellite markers spanning the entire human genome (intermarker distance < 10 cM). Linkage analysis was performed using two-point and multipoint parametric and nonparametric methods. RESULTS: Initial whole genome screening performed with 400 microsatellite markers identified two markers that showed evidence for linkage to AITD in this family, D11S4191 and D9S175, with two-point LOD scores of 2.31 and 2.05, respectively. Multipoint linkage analysis focusing on the regions containing these markers revealed a maximum multipoint LOD score (MLS) of 2.13 and a nonparametric linkage score (NPL) of 6.1 for D11S4191 and an MLS of 2.01 and NPL of 7.5 for D9S175. CONCLUSIONS: These results showed that this Chinese family harboured susceptibility loci for AITD which were distinct from those previously found in the Caucasian population. This suggests that different susceptibility loci exist between different ethnic groups. Furthermore, even within a single family from a genetically homogenous population, more than one gene was involved in the genetic susceptibility to AITD, supporting the notion that AITDs are caused by multiple genes of varying influences.

Adolescent↗