P.1.137 Autoimmune thyroiditis (AIT) and affective disorders — a prospective pilot study

IntroductionInterferon (IFN)-β is known as an environmental trigger for the occurrence of autoimmune thyroid disease (AITD). However, the association of another type-1 IFN, IFN-β, with AITD is unknown.Material and methodsIn the study, we explored the association of serum IFN-β levels with AITD in an ethnic Chinese (i.e., Taiwanese) population. We enrolled 160 patients with Graves’ disease (GD), 47 patients with Hashimoto’s thyroiditis (HT), and 119 healthy controls. Serum IFN-β and B-cell activating factor (BAFF) levels were quantified in healthy controls at the baseline and in patients with AITD either prior to receiving medication or while under medication. Thyroid function and thyroid-stimulating hormone receptor antibody (TSHRAb) levels were measured at the time of serum collection.ResultsSerum IFN-β levels were lower in the HT group than in the control group (p = 0.031). A significant inverse correlation was observed between IFN-β and TSHRAb levels in men with GD (r = –0.433, p = 0.044). Serum IFN-β levels were also negatively associated with BAFF levels in men with GD, HT, and AITD (r = –0.320, p = 0.032; r = –0.817, p = 0.047; and r = –0.354, p = 0.011, respectively), but not in women with GD, HT, or AITD.ConclusionsSerum IFN-β levels were lower in HT patients. Correlations of serum IFN-β with TSHRAb and BAFF levels were found to be gender-specific. Further well-designed studies with larger sample sizes are required to confirm our findings.

Osteopontin (OPN) is recognized as a potent immunoregulator of autoimmune disease. In the study, we tried to explore the association of serum OPN levels with autoimmune thyroid disease, including Graves' disease (GD) and Hashimoto's thyroiditis (HT), in an ethnic Chinese population. We enrolled 131 patients with GD, 33 patients with HT and 123 healthy controls. Serum OPN, B cell-activating factor (BAFF) and interferon (IFN)-α levels were quantified. Graves' disease patients with high thyroid function at the time of sample collection were defined as having active GD, while the other patients were defined as having inactive GD. Serum OPN levels were higher in active GD than in inactive GD and the control groups (P=0.001 and P=0.018, respectively). In GD, significant associations of OPN levels with thyroid-stimulating hormone receptor antibody (TSHRAb) levels were observed in women (r=-0.344, P=0.002, and r=0.440, P=0.004, respectively) but not in men. Osteopontin levels were associated with BAFF levels only in women with GD or HT (r=0.506, P<0.001 and r=0.430, P=0.025, respectively), but not in men with GD or HT. Serum OPN levels were upregulated in active GD, and serum OPN levels were associated with thyroid function and TSHRAb levels in GD. Additionally, OPN levels were correlated with BAFF levels in GD and HT. The associations of OPN levels with clinical phenotypes of GD and BAFF levels showed a dimorphic pattern.

The aim of the study was to determine the clinical meaning of TSH receptor antibody (TRAb) measurement in patients with Graves’ disease (GD). We measured the level of total TRAb using the 1 st generation of enzyme multiplied immunoas# say and studied thyroid status in 30 children with GD at the onset of disease, every 6 months on antithyroid drug therapy and during 12 months after its discontinuation. We investigated the correlation between the changes of thyroid hormones, thyroid volume and TRAb, so as TRAb level and risk of relapse. Results. At disease onset 87% of children presented with “positive” TRAb values, 13% were considered “ambiguous”. TRAb level normalization was evident in 56% patients in mean 13 ± 5 months of therapy, but 23% demonstrated its elevation in future, mean 1.8 ± 0.2 IU/L. TRAb level and thy# roid volume (rs = 0.5, p = 0.01), TRAb and FT4 levels (rs = 0.5, p=0.01) on therapy positively correlated. After discontin# uation of medication in 38.9% of patients thyrotoxicosis relapsed (all patients with TRAb > 10 IU/L, 37.5% of patients with TRAb 1–10 IU/L, and 14.3% with “negative” values). At the onset of disease Ме TRAb was 12.0 (1.42–38.9) IU/L in relapse group and 6.6 (1.43–25.7) IU/L (р > 0.05) in remission group; at the end of the treatment it became 3.85 (0.64–68.9) IU/L and 0.63 (0.12–6.4) IU/L (р = 0.025) respectively. After therapy discontinuation the relapse group trended to TRAb elevation compared to remission group. “Support” methimazole dose was 0.06 ± 0.04 mg/kg/day in remission group and 0.16 ± 0.04 mg/kg/day (р = 0.003) in relapse group. Conclusion. Measurement of TRAb in children with GD is very useful for prediction of disease progression and therapy results. High TRAb level at the onset of disease and at the end of therapy, absence of normalization on therapy are the risk factors for relapse after therapy discontinuation.

Objective: Monocyte chemoattractant protein-1 (MCP-1), serum B-cell activating factor (BAFF), complement B factor (CFB), and anti-M-type phospholipase A2 receptor (PLA2R) antibodies are investigated in connection with membranous nephropathy (MN) and their roles in evaluating the efficacy of treatment. Methods: 108 patients who were hospitalized to our hospital between January 2023 and June 2024 were chosen to serve as research participants. Patients were divided into remission and nonremission groups according to their clinical efficacy. The levels of serum BAFF, CFB, MCP-1 and anti-PLA2R antibodies in patients with positive and negative anti-PLA2R and different pathological stages were compared, and the clinical data of the remission group and the nonremission group were compared. The association between serum levels of BAFF, CFB, and MCP-1 and anti-PLA2R antibody levels in patients who tested positive for anti-PLA2R antibody. The predictive efficacy of serum anti-PLA2R antibodies, BAFF, CFB, and MCP-1 for nonremission in MN patients after therapy was evaluated using receiver operating characteristic (ROC) curves. Results: There were 78 patients who were positive for anti-PLA2R antibodies and 30 patients who were negative for anti-PLA2R antibodies. The levels of serum BAFF, CFB, MCP-1 and anti-PLA2R antibodies in patients positive for anti-PLA2R antibodies were significantly greater than those in patients negative for anti-PLA2R antibodies (P&lt;0.05). The comparison of the serum BAFF, CFB and MCP-1 levels in MN patients at different stages were as follows: stage I &lt; stage II &lt; stage III &lt; stage IV. Serum BAFF, CFB, and MCP-1 in patients positive for anti-PLA2R antibodies were positively correlated with the level of anti-PLA2R antibodies (r=0.792, 0.823, 0.832, P&lt;0.001). Spearman correlation analysis revealed that the levels of serum BAFF, CFB, and MCP-1 in MN patients were positively correlated with pathological stage (rs=0.758, 0.752, 0.717, P&lt;0.001). The pathological stage and anti-PLA2R antibody, BAFF, CFB and MCP-1 levels in the nonremission group were significantly greater than those in the remission group (P&lt;0.05). After treatment, elevated serum levels of MCP-1, CFB, and BAFF were risk factors for nonremission in MN patients (P&lt;0.05). The ROC curve analysis revealed that the area under the curve for the combined prediction of nonremission in MN patients after treatment with serum BAFF, CFB and MCP-1 was 0.948, which was greater than the area under the curve for the individual prediction of anti-PLA2R antibody and BAFF, CFB and MCP-1 (Z=4.116, 3.059, 4.122, 4.116, P&lt;0.05). Conclusion: The levels of serum BAFF, CFB and MCP-1 in MN patients are related to the level of anti-PLA2R antibody, MN stage and therapeutic effect. Moreover, the combined detection of serum BAFF, CFB and MCP-1 has high predictive value for the nonremission of MN patients after treatment.

Dysregulation of factors vital to the survival B cells and/or plasma cells, such as BAFF and APRIL, could be detrimental to a pregnancy. Serially collected first-, second-, and third-trimester serum samples were measured for BAFF and APRIL by ELISA from 150 pregnant women (71 healthy + 79 with a chronic medical disease) at a single medical center. Postpartum serum samples were also collected from the majority of these women. Matched third-trimester and cord blood samples were collected from 168 women (86 healthy + 82 with a chronic medical disease). Data were analyzed by chi-square statistic, unpaired t-test, paired t-test, Mann-Whitney rank sum test, Wilcoxon signed rank test, Spearman rank order correlation, and receiver operator characteristic (ROC) curve analyses as appropriate. Maternal serum BAFF levels declined as the pregnancies progressed and rebounded postpartum, whereas serum APRIL levels remained relatively flat throughout pregnancy and postpartum. Cord BAFF and APRIL levels correlated positively with gestation age and were considerably greater than the corresponding maternal third-trimester serum BAFF and APRIL levels, respectively. In women who developed preeclampsia, third-trimester BAFF levels were greater, rather than lower, than their corresponding second-trimester BAFF levels. ROC curve analysis suggested a potential role for third-trimester serum BAFF level as a biomarker of preeclampsia. BAFF and APRIL are differentially regulated in the mother during and following pregnancy, whereas each is upregulated in the developing fetus. An increase in third-trimester serum BAFF level may portend development of preeclampsia.

Background/Objectives: We aimed to explore long-term trajectories of thyroid-stimulating hormone receptor antibody (TRAb) in patients with Graves' disease (GD) and to identify key factors associated with TRAb normalization. We also investigated whether these trajectories correlate with Graves' orbitopathy (GO) comorbidity. Methods: We retrospectively reviewed 403 patients with GD who had an initial TRAb level ≥ 1.5 IU/L between 2010 and 2021, monitoring their TRAb levels for at least 3 years. K-means clustering was performed to categorize patients into distinct TRAb change patterns (A, B, C, D). We employed a Cox regression-based time-to-event model, expressing results as "Survival ratio" rather than the conventional Hazard ratio, to reflect the proportion of patients achieving TRAb normalization over time. Key variables included age, sex, initial TRAb, and GO comorbidity. Results: Four unique TRAb patterns emerged, differing primarily in baseline TRAb levels, duration of GD, and treatment approaches. Pattern A demonstrated the highest TRAb normalization rate (96%), whereas Patterns B (80%), C (29%), and D (13%) showed lower probabilities. Regrouping into A vs. BCD further emphasized the distinct normalization profile of Pattern A. A higher "Survival ratio" was observed in female patients and those with baseline TRAb < 6.14 IU/L. In contrast, patients whose TRAb levels were ≥6.14 IU/L frequently exhibited persistently elevated values over a decade. GO comorbidity did not significantly differ among the four patterns. Conclusions: K-means clustering revealed four unique TRAb change patterns in GD, with baseline TRAb (stratified by the median of 6.14 IU/L) and sex emerging as significant predictors of normalization. These findings highlight the importance of early TRAb monitoring and tailored therapeutic strategies, particularly for those with persistently elevated TRAb levels.

Thyroid function in autoimmune thyroid disease (AITD) among patients with Down syndrome (DS) sometimes exhibits fluctuations over time, but the underlying cause of this variability remains unknown. Thyrotoxicosis is often associated with Graves disease (GD) and Hashitoxicosis. Thyroid-stimulating hormone (TSH) receptor antibody (TRAb) includes thyroid-stimulating antibody (TSAb) and TSH-stimulation blocking antibody (TSBAb), causing GD or hypothyroidism, respectively. We report two patients of DS showing discordance between thyroid function and TRAbs. Case 1: A 16-year-old boy with DS was diagnosed with Hashimoto thyroiditis at age 6, with positive TSAb and TSBAb. At age 7, GD was diagnosed based on thyrotoxicosis and elevated I123 uptake. His TRAb became negative after 18 months of methimazole treatment. During follow-up, recurrent thyrotoxicosis with positive TRAb/TSAb improved transiently without intensified treatment. Methimazole was discontinued at age 14, but hypothyroidism with positive TSAb and negative TSBAb became evident. Case 2: An 18-year-old woman with DS was diagnosed with Hashimoto thyroiditis at age 13. She experienced recurrent transient thyroiditis with positive TRAb/TSAb. Although TSAb remained positive and TSBAb negative, hypothyroidism continued without GD. In conclusion, our findings indicate that awareness of the potential discordance between TSAb/TSBAb status and thyroid function is important for deciding appropriate treatment in DS patients with unstable thyroid function and AITD.

BackgroundGraves’ disease (GD) is the most common cause of hyperthyroidism, and it rarely develops in patients who undergo partial thyroid removal for thyroid cancer. The present study characterized and analyzed the GD development mechanism after partial thyroidectomy for thyroid cancer and suggested optimized treatments for the condition.MethodsA retrospective study from January 2013 to March 2017 was conducted in patients where GD occurred after partial thyroidectomy for thyroid cancer. Reviewed laboratory data included free 3,5,3'-triiodothyronine, free thyroxine, thyroid-stimulating hormone (TSH), thyroglobulin (Tg), anti-Tg antibody, anti-peroxidase antibody, and TSH receptor antibody levels. All laboratory indicators included preoperative and postoperative data. In addition, we collected patient neck ultrasound examination records and radioiodine (RAI) uptake test data.ResultsAmong 5,600 patients diagnosed with GD, 5 (0.09%) met the inclusion criteria and were enrolled. Patient mean age was 47.4±9.6 years, and all were female with a papillary thyroid carcinoma stage I diagnosis. The interval between partial thyroidectomy and hyperthyroidism onset ranged from 2 to 25 months. We proposed possible mechanisms for this medical condition and identified several factors accelerating the disease course. To treat GD, a low RAI (30 mCi) dose was prescribed to patients. All exhibited hypothyroidism at a 3- or 6-month follow-up, with stable clinical status at 1-year follow-up.ConclusionsGD rarely develops after partial thyroidectomy for thyroid cancer. We recommend a low RAI dose to manage GD and ablate the remnants of thyroid cancer.

To assess the association of tumour necrosis factor-α (TNF-α) gene polymorphisms at positions -863C/A, -857C/T, -238G/A and Graves disease (GD) susceptibility in Chinese Han population in Anhui region. The polymorphisms of TNF-α gene were determined by polymerase chain reaction with specific primers in 254 patients affected with GD and 212 healthy controls. Allelic and genotypic frequencies in GD group and normal controls as well as in different genders were compared. The allelic and genotypic frequencies for different thyroid stimulating hormone receptor antibody (TRAb) levels (TRAb > 12 U/L; ≤12 U/L) were also compared among patients with earlier onset GD. (1) The A allele at -863C/A locus in GD group (16.73%) was significantly greater than that of the control group (11.79%) (P< 0.05, OR = 1.503); the frequency of AA+CA genotype of -863C/A locus in GD group (32.68%) was significantly greater than that of control group (23.58%) (P< 0.05, OR = 1.573). There was no significant difference (P> 0.05) in the allelic and genotypic frequencies of -857C/T, -238G/A loci between the two groups. (2) There was no significant difference (P> 0.05) in the allelic and genotypic frequencies of -863C/A, -857C/T, -238G/A loci between patients of different genders. (3) There was no significant difference (P>0.05) in such frequencies between patients with earlier onset GD and different TRAb levels (TRAb > 12 U/L; ≤12 U/L). (1) The -863 A allele of TNF-α gene may contribute to the development of GD in Chinese Han population in Anhui, whilst -857C/T, -238G/A alleles may not. (2) There is no association between TNF-α gene -863C/A, -857C/T, -238G/A polymorphisms and development of GD in different genders. (3) There was no association between above polymorphisms and TRAb levels in patients with earlier onset GD.

Background:B-cell activating factor (BAFF) is vital for B cell survival. Serum BAFF levels are elevated in thrombotic antiphospholipid syndrome, but little is known about levels in patients with positive antiphospholipid antibodies (aPLs) and previous adverse pregnancy outcomes (APOs). We aimed to analyze serum BAFF concentrations of these patients in early pregnancy along with different pregnancy outcomes.Methods:Thirty-six pregnant patients positive for aPLs and previous APOs (patient group), 25 healthy pregnant females (HP group) and 35 healthy non-pregnant females (HNP group) from the Peking University Third Hospital, between October 2018 and March 2019, were enrolled in this study. Serum of HNP and serum of patients as well as HP in the first gestational trimester were collected. Enzyme-linked immunosorbent assay kits were used to measure serum BAFF and interferon-alpha (IFN-α) concentrations. Cytometric bead array analysis was used to measure serum concentrations of cytokines. The patient group was further divided into APOs and non-APOs (NAPOs) group, fetal loss and live birth group according to pregnancy outcomes. The Mann-Whitney U-test was used to assess significance between and within groups. Spearman rank-order was used to evaluate correlation coefficients between BAFF and related cytokines.Results:The serum BAFF level in HP group was significantly lower than HNP group (245.24 [218.80, 265.90] vs. 326.94 [267.31, 414.80] pg/mL, Z = −3.966, P < 0.001). The BAFF level was obviously elevated in patient group compared to that in HP group (307.77 [219.86, 415.65] vs. 245.24 [218.80, 265.90] pg/mL, Z = −2.464, P = 0.013). BAFF levels in APOs group tended to be higher than that in NAPOs group (416.52 [307.07, 511.12] vs. 259.37 [203.59, 375.81] pg/mL, Z = −2.718, P = 0.006). Compared to HP group, concentrations of IFN-α, interleukin (IL-6) and tumor necrosis factor were higher in patient group (33.37 [18.85, 48.12] vs. 13.10 [6.85, 25.47] pg/mL, Z = −2.023, P = 0.043; 39.16 [4.41, 195.87] vs. 3.37 [2.92, 3.90] pg/mL, Z = −3.650, P < 0.001; 8.23 [2.27, 64.46] vs. 1.53 [1.25, 2.31] pg/mL, Z = −3.604, P < 0.001, respectively). Serum BAFF levels had a positive correlation with the concentrations of both IL-6 and IL-10 (IL-6: r = 0.525, P = 0.002; IL-10: r = 0.438, P = 0.012).Conclusions:Serum BAFF levels are increased in patients with positive aPLs and previous APOs as compared to healthy pregnant females and tend to be higher in individuals with current APOs. The BAFF levels have a positive correlation with serum IL-6 and IL-10.

AB0343 Thyroid Autoantibodies in Seropositive Versus Seronegative Rheumatoid Arthritis: Is There a Link?

Objectives The objective of the study is to observe changes in choroidal thickness (CT) in patients with Graves' ophthalmopathy using spectral-domain optical coherence tomography (SD-OCT). Methods The right eyes of 36 patients (27 females and 9 males) with Graves' ophthalmopathy (GO) and those of 36 age-, gender-, and diopter-level-matched healthy participants were evaluated. The patients' data were obtained within 3 months after the onset of Graves' disease (GD). Thyroid hormone levels and thyroid-stimulating hormone receptor antibody (TRAb) levels were measured, and the degree of exophthalmos was measured in all patients. Activity is measured by the clinical activity score (CAS). A horizontal scan centered on the fovea was performed in all participants. Five points of choroidal thickness were measured at the fovea (SFCT) and at 1500 μm nasal (N1500), 3000 μm nasal (N3000), 1500 μm temporal (T1500), and 3000 μm temporal (T3000) to the fovea. Results The CT measurements obtained were (mean ± SD) 313.47 ± 100.32 μm, 279.22 ± 85.80 μm, 214.64 ± 75.52 μm, 313.19 ± 80.36 μm, and 298.14 ± 82.75 μm in patients with GO and were 256.33 ± 50.18 μm, 223.14 ± 59.61 μm, 176.69 ± 60.66 μm, 250.92 ± 52.184 μm, and 239.47 ± 60.35 μm in the control group at the foveal, N1500, N3000, T1500, and T3000 measurement points, respectively. The CT in GO patients was significantly increased at all the points compared with the control group (P < 0.05). There was no relationship between the CT and CAS, the degree of exophthalmos, triiodothyronine (T3), tetraiodothyronine (T4), thyroid-stimulating hormone (TSH), or TRAb levels in GO. Conclusions CT was found to be increased in GO patients and had poor relationship with CAS, exophthalmos, and thyroid function tests.

Pretransplant serum BAFF levels are associated with pretransplant HLA immunization and renal allograft survival

Introduction Acute lymphoblastic leukemia (ALL) is a biologically heterogeneous disorder needing determination of morphologic, immunologic, cytogenetic, biochemical, and molecular genetics characterizations of lymphoblasts to establish diagnosis. Microenvironmental cues play critical roles in cancer biology and malignant cells are responsive to multiple extrinsic factors. There is emerging evidence that B-cell activating factor (BAFF) is a critical factor for the growth and survival of both normal and malignant clones of B-cells and can augment tumor cell growth. There is evidence that B-lineage neoplasms have aberrant expression of BAFF. Objectives The aim of this study was to evaluate serum BAFF levels to assess its prognostic impact on ALL and correlate it with mortality. Patients and methods The study was conducted at Ain Shams University on 40 ALL pediatric and adult patients, in addition to 20 controls. Patients underwent detailed history and clinical examination, bone marrow examination, and evaluation of serum BAFF levels using enzyme-linked immunosorbent assay. Thereafter, they were assessed for treatment response and patients' mortality on day 28 from induction of chemotherapy and after 6 months, respectively. Results We found a statistically significant lower BAFF levels among controls compared with the patient group, in which there was no significant difference between pediatric and adult subgroups. High serum BAFF was significantly correlated to patients' poor treatment response but not mortality. Conclusion High BAFF in our studied patients may be explained by its role in augmenting B-cell tumor growth. In our study, we found that BAFF had no relation with disease outcome. This may be caused by the limited number of patients included. Assessment of BAFF level at the time of diagnosis may be a predictor for response to treatment, as we found a significant relation between BAFF level and response to treatment. This finding recommends that patients with high BAFF level at the time of diagnosis be subjected to intensified course of therapy.

We report on a sudden cardiac death case involving a 40-year-old man with no known medical history. Forensic autopsy showed lymphocytic myocarditis associated with lymphocytic thyroiditis. In both the heart and the thyroid gland, the inflammatory foci often had a nodular pattern with a germinal centre. Virological and toxicological analyses were negative. Postmortem biochemistry showed a slight increase in TSH in combination with normal T3 and T4 blood levels suggesting hypothyroidism. High titres of antiperoxidase and antithyroglobulin antibodies with normal levels of TSH receptor antibodies, in addition to biological hypothyroidism and lymphocytic inflammation were consistent with the diagnosis of Hashimoto's thyroiditis. Immunohistochemical studies excluded a lymphoma and showed no evidence of viral myocarditis. In contrast to Grave's disease, Hashimoto's thyroiditis has never been reported in association with myocarditis as a cause of sudden death. We conclude that the cardiac immunological and histological pattern, similar to that found in the thyroid gland suggests an autoimmune myocarditis.