anti-TPO Abs Research Articles

Anti-thyroid Antibodies in Bipolar Disorder

Dysfunction of the hypothalamus-pituitary-thyroid axis has been shown to play a role in the pathophysiology of bipolar disorder. Autoimmune thyroiditis is the most common cause of thyroid function alteration. Thus, auto-immune thyroiditis is likely associated with bipolar disorder. It might influence its course, prognosis and/or management. To study the prevalence of positive anti-thyroid antibodies in patients with bipolar disorder and to examine the prognostic and the therapeutic implications of their presence. Literature was reviewed using the Medline database and the following keywords: ‘bipolar disorder” ‘antithyroid antibodies” ‘thyroiditis”. PubMed research returned 12 results. After manual inspection, 10 articles were retained and examined. The prevalence of positive antithyroperoxydase antibodies (anti-TPO Abs) is higher in bipolar patients than in healthy controls, reaching 27%. The presence of positive anti-TPO Abs has been associated with rapid-cycling, with a higher risk of lithium-induced hypothyroidism as well as with poor prognosis. Auto-immune thyroiditis appears to be related not only to bipolar disorder itself but also to the genetic vulnerability to develop the disorder. The presence of anti-TPO Abs is a possible endophenotype for bipolar disorder. Anti-TPO Abs should be obtained in many patients with bipolar disorder, especially in those on lithium.

Pregnancy Outcome in Euthyroid Women with Anti-Thyroid Peroxidase Antibodies.

The aim of this study was to compare pregnancy outcomes in euthyroid women who were anti-TPO Ab(+) with those who were anti-TPO Ab(-). This observational study comprised 1,000 women in the age group of 25-35years, having normal thyroid function tests, normotensive, non-diabetic, singleton pregnancy and attending Gyn. OPD/ANC up to 20weeks' gestation and those who were already in the process of abortion. anti-TPO Ab levels of >50IU/ml were considered as anti-TPO Ab(+). This study was conducted in the SMS Medical College's attached hospital, Jaipur from April 2012 to September 2013. The estimation of the proportion of anti-TPO Abs in the hospital-based population and the comparison of pregnancy and neonatal outcomes in anti-TPO Ab(+) and Ab(-) euthyroid women were done. The main result showed increased rates in miscarriages (13.33 vs. 2.34%, P<0.001), LBWs (25 vs. 5.12%, P<0.001), preterm deliveries [<34weeks] (5 vs. 1.80%, P>0.05) in anti-TPO Ab(+) women. The current study revealed that anti-TPO Abs are strongly associated with miscarriage and LBW irrespective of their gestational age. However, we did not find any correlation with the other complication as found in the studies by Abbassi-Ghanavati, Negro et al.

Insulin resistance in hypothyroid patients under Levothyroxine therapy: a comparison between those with and without thyroid autoimmunity.

BackgroundA chronic inflammation resulting from an imbalance between pro-inflammatory and anti-inflammatory cytokines in Hashimoto’s thyroiditis (HT) might be responsible for IR in hypothyroidism. This study was performed to investigate a probable association between autoimmune background of hypothyroidism and IR.MethodsIn this clinical study, 63 subjects with Hashimoto’s thyroiditis and 49 subjects with post-ablation hypothyroidism were enrolled. All the participants were euthyroid for more than one year through Levothyroxine therapy. Serum concentrations of Thyroid-stimulating Hormone (TSH), Free Thyroxin (FT4, FT3), Anti-Thyroid Peroxidase Antibodies (Anti-TPO Abs), Total Cholesterol (TC), HDL-Cholesterol (HDL-C), Triglyceride (TG), Fasting Blood Glucose (FBG), and insulin levels were measured and Oral Glucose Tolerance Test (OGTT) was performed for all of the subjects. Participants with anti TPO levels more than 1000 IU /ml were classified as having highly positive antibodies.ResultsNo significant differences regarding to plasma insulin, glucose and lipid concentration, were detected between subjects with and without Hashimoto’s thyroiditis. However, subjects with highly positive Anti TPO Abs had higher prevalence of elevated fasting insulin level than those with lower titers of Anti TPO Abs and subjects without autoimmune background (94.1% vs. 62.8% and 71.4% respectively, P = 0.05). Subjects with highly positive titers of Abs also had a lower serum HDL-c levels than the rest of the subjects (40.6 ± 2.1 vs. 47.2 ± 1.7 and 47.4 ± 1.4, P = 0.04).ConclusionsThere is no obvious association between thyroid autoimmunity and metabolic indexes of hypothyroid patients. Only patients with Ani TPO antibody levels more than 1000 IU/ml may experience higher insulin level and less HDL-c with the same BMI.

Thyroid functions and autoimmunity in Egyptian children with chronic hepatitis C virus infection before interferon treatment

Background: The association of thyroid dysfunction with hepatitis C virus (HCV) infected children who are on interferon therapy is well established. But thyroid functions in untreated chronic HCV children is an aspect which the present study intended to explore. Settings and Design: Cross-sectional controlled study. Materials and Methods: The study included 30 children with chronic hepatitis C (Group 1; mean age 9.86 ± 2.22 years). Thirty healthy children age- and sex-matched were included as control group (Group 2; mean age 8.54 ± 2.31 years). Measurement of thyroid stimulating hormone (TSH), free thyroxine (FT 4 ), and free triiodothyronine (FT 3 ), as well as anti-thyroid peroxidase antibodies (TPO Ab) and anti-thyroglobulin (Tg Ab) were done. Results: Mean TSH levels were significantly higher in the group 1 as compared to control (P < 0.001). Subclinical hypothyroidism was detected in 13.3% in the study group vs 3.3% in the control group (P < 0.001). Positive levels of TPO Ab and Tg Ab were found to be 23.3% and 13.3% in Group 1 compared with 6.6% and 3.3% in controls, respectively. We also observed a significant positive correlation between TSH levels and age, HCV duration, viral load, anti-TPO Abs, antiTg Abs, and negative correlation with FT4. Conclusions: Both subclinical hypothyroidism and thyroid autoimmunity are common in Egyptian children with chronic hepatitis C before interferon treatment.

Does the presence of thyroid antibodies affect the course and outcome of pregnancy in type 1 diabetic women?

The aim of the study was to evaluate the significance of the presence of thyroid peroxidase autoantibodies (anti-TPO Abs) in type 1 diabetes mellitus (DM1) pregnant women relative to the course of pregnancy and, especially, with regard to metabolic control, thyroid function, maternal complications and neonatal outcome. In a prospective observational study of 91 DM1 women with singleton pregnancies, anti-TPO, anti-thyroglobulin, thyroid-stimulating hormone (TSH), and free thyroxine index (T4/thyroid binding capacity) were measured in each trimester. At each visit, HbA1c, body mass index, and units of insulin per kilogram were recorded, as were complications and pregnancy outcome. Twenty-one (27%) of the 78 women who met the inclusion criteria presented with positive anti-TPO Abs. There were no differences regarding glycemic control (HbA1c) or insulin dose. First-trimester TSH levels were significantly higher in the anti-TPO-positive group than in the anti-TPO-negative group. Finally, no differences were observed regarding diabetic or obstetric complications and neonatal outcome. One fourth of DM1 pregnant women presented with positive anti-TPO Abs. However, the presence of anti-TPO Abs does not seem to be related with worse metabolic control or adverse pregnancy outcome. Further investigation is needed; meanwhile, the effort for early treatment of thyroid dysfunction and strict metabolic control in all DM1 women should be continued.

English

BACKGROUND: The appearance of TPO-Abs precedes thyroid dysfunction and increases in autoimmune diseases like type1diabetes.Thyroid peroxidase (TPO) antibodies are one of the major secondary antibodies associated with autoimmune thyroid disease and can be used as diagnostic marker. The prevalence of thyroid auto antibodies is increased when patients have non-thyroid autoimmune diseases such as type 1 diabetes and pernicious anemia. Thyroid dysfunction is common among diabetic patients and can produce metabolic disturbances. Therefore, regularly screening diabetic patients allows early treatment. OBJECTIVE: The objective of our study is to measure TPO-Abs in young Type-1Diabeticindividuals and to find Thyroid abnormalities in TPO-Abs positive individuals. MATERIALS AND METHODS: This was a cross-sectional study conducted at a rural clinic in Tiruchirappalli, Tamil Nadu. 60 persons in the age group of 10 to 35 years were selected for this study. Fasting blood samples were collected from the study population and glucose, lipid profile, thyroid profile and TPOAb were estimated using standard kits by standard methods. RESULTS:16 persons showed high levels of anti TPO-Abs(> 40 IU).In the anti TPO-Ab Positive group, all values were statistically significant according to the Pearson R formula P < 0.001. There was significant correlation between age and anti TPO-Ab level, between weight, BMI and TPO Positive and Negative levels, as per the TTest P <0.001.56.30% of anti TPO-Ab Positive subjects had high TSH. CONCLUSION: Our results indicate that thyroid dysfunctionis common in Type-1 diabetes but more in anti TPO-Ab positive subjects. Hence all Type-1 diabetic individuals should undergo annual screening of serum anti TPO-Ab and TSH measurement in anti TPO-Ab positive individuals.

Anti-erythropoietin and anti-thrombopoietin antibodies induced after administration of recombinant human erythropoietin

Recombinant human erythropoietin (rhEPO) has been successfully used for correcting renal anemia. However, recent studies have raised some concerns about the safety of rhEPO treatment due to its immunogenic side effect — pure red cell aplasia (PRCA). We now report a case of development of anti-EPO neutralizing antibodies (Abs) implicated in thrombocytopenia as well as erythrocytopenia. A 35-year-old man had a history of administering rhEPO (epoetin alfa, epoetin beta and darbepoetin alfa) for 2years to treat renal anemia. The hematological parameters were collected. Anti-EPO, anti-platelet, and anti-thrombopoietin (TPO) Ab assays were performed to test the presence of autoreactive Abs. After performing antibody assays due to severe resistance to rhEPO treatment, a high titer of anti-EPO neutralizing Abs was detected. However, unexpectedly, this patient also showed thrombocytopenia rather than PRCA. We investigated the cause of the marked thrombocytopenia and found anti-TPO Abs in patient serum. To our best knowledge, this is the first report of the development of anti-TPO Abs during rhEPO treatment for anemia.

Superiority of thyroid peroxidase DNA over protein immunization in replicating human thyroid autoimmunity in HLA-DRB1*0301 (DR3) transgenic mice.

Murine experimental autoimmune thyroiditis (EAT), characterized by thyroid destruction after immunization with thyroglobulin (Tg), has long been a useful model of organ-specific autoimmune disease. More recently, porcine thyroid peroxidase (pTPO) has also been shown to induce thyroiditis, but these results have not been confirmed. When (C57BL/6 x CBA)F(1) mice, recently shown to be susceptible to mouse TPO-induced EAT, were immunized with plasmid DNA to human TPO (hTPO) and cytokines IL-12 or GM-CSF, significant antibody (Ab) titres were generated, but minimal thyroiditis was detected in one mouse only from the TPO + GM-CSF immunized group. However, after TPO DNA immunization of HLA-DR3 transgenic class II-deficient NOD mice, thyroiditis was present in 23% of mice injected with TPO + IL-12 or GM-CSF. We also used another marker for assessing the closeness of the model to human thyroid autoimmunity by examining the epitope profile of the anti-TPO Abs to immunodominant determinants on TPO. Remarkably, the majority of the anti-TPO Abs was directed to immunodominant regions A and B, demonstrating the close replication of the model to human autoimmunity. TPO protein immunizations of HLA-DR3 transgenic mice with recombinant hTPO did not result in thyroiditis, nor did immunization of other mice expressing HLA class II transgenes HLA-DR4 or HLA-DQ8, with differential susceptibility to Tg-induced EAT. Moreover, our efforts to duplicate exactly the experimental procedures used with pTPO also failed to induce thyroiditis. The success of hTPO plasmid DNA immunization of DR3(+) mice, similar to our reports on Tg-induced thyroiditis and thyrotropin receptor DNA-induced Graves' hyperthyroidism, underscores the importance of DR3 genes for all three major thyroid antigens, and provides another humanized model to study autoimmune thyroid disease.

Thrombopoietin (TPO) Knockout Phenotype Induced by Cross-Reactive Antibodies Against TPO Following Injection of Mice with Recombinant Adenovirus Encoding Human TPO

Adenovirus vectors have emerged as potent agents for gene transfer. Immune response against the vector and the encoded protein is one of the major factors in the transient expression following in vivo gene transfer. A single injection of an adenovirus encoding human thrombopoietin (TPO) into mice induced transient thrombocytosis, followed by a chronic immune thrombocytopenia. Thrombocytopenic mice had anti-human TPO Abs of the IgG2a and IgG1 isotypes. Thrombocytopenic mice sera neutralized more efficiently human than murine TPO, and exhibited no detectable anti-murine TPO Abs. Despite their low affinity for murine TPO, anti-TPO Abs induced a TPO knockout-like phenotype, i.e., low number of marrow megakaryocytes and of all kinds of hemopoietic progenitors. Hybridomas derived from a thrombocytopenic mouse revealed cross-reactivity of all of the secreted anti-TPO Ab isotypes. Mice subjected to myelosuppression after virus injection showed that anti-human TPO of IgG1 and IgG2a isotypes disappeared. Thus, sustained human TPO production was responsible for platelet elevation for at least 5 mo. Compelling results showed that elevated IgG2a/IgG2b ratios are always associated with thrombocytopenia, whereas low ratios are associated with tolerance or normal platelet counts. Finally, we hypothesize that in humans some chronic thrombocytopenia associated with a low TPO plasma level are due to anti-TPO Abs.