Thyroid-infiltrating lymphocytes, thyroid function, and HLA-DR in juvenile autoimmune thyroiditis

1989 ◽  
Vol 121 (4) ◽  
pp. 573-577 ◽  
Author(s):  
Jorma Mäenpää ◽  
Irmeli Lautenschlager ◽  
Marcus Nyberg ◽  
Saija Koskimies ◽  
Sirkka Kontiainen

Abstract. Eighteen patients with juvenile autoimmune thyroiditis were studied. At diagnosis 8 (44%) of the patients were euthyroid and 10 hypothyroid, whereas at the end of 6 to 12 months follow-up, 12 (66%) were euthyroid and 6 hypothyroid. All the patients were HLA-typed. The frequency of HLA-DR4 was increased in the patients when compared with the normal population, 63 vs 28% (p < 0.01). An analysis of thyroid-infiltrating mononuclear cells revealed that the majority of the thyroid-infiltrating lymphocytes were T cells. More T lymphocytes and fewer B lymphocytes and HLA class II positive lymphocytes were found among the thyroid-infiltrating mononuclear cells in euthyroid than hypothyroid patients. The numbers of thyroid-infiltrating B lymphocytes correlated with the levels of thyroid microsomal antibodies. No correlation was found between thyroid function and thyroid antibodies.

2018 ◽  
Vol 127 (05) ◽  
pp. 281-288 ◽  
Author(s):  
Mario Štefanić ◽  
Stana Tokić ◽  
Mirjana Suver-Stević ◽  
Ljubica Glavaš-Obrovac

Abstract Background Co-inhibitory receptors (IR), such as TIGIT and FCRL3, provide a checkpoint against highly destructive immune responses. Co-expression of TIGIT and FCRL3, in particular, has been linked to the HELIOS+ subset of regulatory CD4+FOXP3+T-cells. Of these, CD4+FOXP3-exon(E)2+ cells have higher expression of IR and exhibit strongest suppressive properties. Nevertheless, how the expression of TIGIT, FCRL3, HELIOS, and FOXP3E2 is regulated in chronic autoimmune thyroiditis (AT), is not known. Methods Thirty patients with AT [encompassing spontaneously euthyroid (euAT), hypothyroid-untreated and L-thyroxine-treated cases)] and 10 healthy controls (HC) were recruited. FCRL3, TIGIT, HELIOS and FOXP3E2 mRNA expression levels in peripheral blood (PB) T cells were measured via quantitative real-time PCR and compared to clinicopathological factors. Results The TIGIT and FCRL3 expression levels from T cells of AT cases were inversely related to the thyroid volume, and were significantly increased in hypothyroid patients (on+off L-thyroxine), but not euAT cases. The FCRL3 expression in PB T cells positively correlated with thyroid-peroxidase autoantibody levels; by contrast, T cells from aged AT patients and combined samples (AT+HC) accumulated more TIGIT mRNA. The patients with higher TIGIT mRNA levels had a greater prevalence of hypothyroidism, showing higher peak thyrotropin levels at diagnosis or at follow-up. Conclusions Multiple IR, namely FCRL3 and TIGIT, but not the transcription factors HELIOS and FOXP3E2, showed increased mRNA levels in PB T cells from end-stage, long-standing and/or more aggressive AT, in proportion to disease severity. A relation with major clinical subphenotypes was observed, thereby identifying IR as potentially important players in AT.


1983 ◽  
Vol 104 (2) ◽  
pp. 195-200 ◽  
Author(s):  
Per Anders Dahlberg ◽  
Rolf Jansson

Abstract. During a 4 year period 19 women with post-partum onset of thyroid dysfunction have been seen in our clinic. Five women had high radioiodine uptake thyrotoxicosis (Graves' disease). Twelve women had hypothyroid symptoms starting within 3–6 months of delivery. All of these women had thyroid microsomal and/or cytoplasmic autoantibodies and thyroid lymphocytic infiltration suggesting aggravation of pre-existing subclinical autoimmune thyroiditis (Hashimoto's disease). At follow-up thyroid function gradually improved in all but signs of persistent thyroid hypofunction remained in seven. Thus women developing symptomatic postpartum hypothyroidism should be followed regularly and when thyroxine treatment is commenced in the post-partum period, it has to be continued indefinitely in many cases. Two women presented with transient low radioiodine uptake thyrotoxicosis and a small painless goitre. Thyroid cytology revealed thyroiditis but they had no thyroid autoantibodies. When followed after a succeeding delivery none of these women developed post-partum thyroid dysfunction in contrast to women in the autoimmune group. Probably the aetiology of thyroid dysfunction in these 2 women was different.


2011 ◽  
Vol 164 (3) ◽  
pp. 317-323 ◽  
Author(s):  
Jesper Karmisholt ◽  
Stig Andersen ◽  
Peter Laurberg

Subclinical hypothyroidism (SCH) is a common condition that is often observed without therapy. However, no evidence-based recommendation exists with regards to how patients with untreated SCH should be monitored.Monitoring involves regular assessment of symptoms and signs of hypothyroidism (HYPO) and biochemical tests of thyroid function. An important question when repeated tests of thyroid function are performed is how large a difference in test results is needed to be confident that the change is real and not just due to chance variation.Recent data show that the least significant difference between two tests in SCH is 40% for TSH and 15% for free thyroxine and free triiodothyronine, with 90% confidence. Furthermore, monitoring has to be based on biochemical function testing because serial evaluation of symptoms and signs related to HYPO is rather insensitive in detecting worsening of thyroid insufficiency.When the presence of thyroid peroxidase auto-antibodies (TPO-Ab) in serum has been demonstrated, repeated measurements do not add much useful information in the monitoring of individual subclinical hypothyroid patients, as levels of TPO-Ab vary in parallel with TSH in these patients.Lastly, we discuss how differences in the monitoring procedure influence the diagnostic outcome, and we suggest a follow-up approach for untreated subclinical hypothyroid patients.


2004 ◽  
Vol 10 (1) ◽  
pp. 16-25 ◽  
Author(s):  
Yassir Hussien ◽  
Alessandra Sanna ◽  
Mats Söderström ◽  
Hans Link ◽  
Yu-Min Huang

Current therapy of multiple sclerosis (MS) with interferon-beta (IFN-b) or glatiramer acetate (GA) has modest effects on the course of MS. Both compounds affect several immune variables, like expression of cell surface molecules and cytokine levels. Here we compared untreated MS, therapy with IFN-b alone and combined with GA, and healthy controls (HC), regarding expression on HLA -DR+ blood mononuclear cells (MNC) of C D1a that is a cell surface molecule with capacity to present glycolipids to T cells, and of C D80 and C D86 which are costimulatory molecules that activate Th1 and Th2 responses. C ytokine production by MNC was also measured. Flow cytometry and ELISA were used. C ross-sectional comparisons revealed that untreated MS patients had higher C D1a+ HLA -DR+ MNC and lower IL-10 production compared to patients treated with IFN-b or IFN-b+G A or HC. Untreated MS patients also had higher spontaneous IFN-g and IL-12p70 production compared to MS patients treated with IFN-b+G A or HC, but not when compared to MS patients on monotherapy with IFN-b. Low C D1a+ HLA -DR+ MNC and low spontaneous production of IL-12p70 and IFN-g were more pronounced in patients treated with IFN-b+G A than with IFN-b alone. In order to clarify whether these changes reflect disease activity or treatment effects, we performed a follow up study. Nineteen MS patients with disease progression, despite monotherapy with IFN-b for more than one year, were re-examined after one to three and four to six months of treatment with IFN-b+G A. This combination therapy was associated with normalization of C D1a+ HLA -DR+ MNC, IL-12p70 and IFN-g. It remains to be shown whether these immunological changes imply a clinical benefit. Follow up studies of immune variables versus clinical effects during combined therapy of MS with IFN-b+G A are ongoing.


Pteridines ◽  
1990 ◽  
Vol 2 (1) ◽  
pp. 17-21
Author(s):  
Gilbert Reibnegger ◽  
Hubert A. Denz ◽  
Dietmar Fuchs ◽  
Lothar C. Fuith ◽  
Claus Gattringer ◽  
...  

Summary Urine concentrations of neopterin, a marker for the activation of cellular immunity, were determined concomitantly with a large panel of hematological and immunological variables on 24 women with gynaecological cancers (12 uterine cervix, 5 endometrium, 7 ovary). There were 14 women investigated at first diagnosis of carcinoma, and 10 women were studied during follow-up (evidence of disease, only palliative treatment during the preceding three months). A statistically significant correlation was found between neopterin concentrations and number of circulating non-B lymphocytes expressing HLA-DR antigen. Neopterin concentrations, numbers of HLA-DR positive cells, and numbers of circulating leukocytes were significantly higher in women studied during follow-up, when compared with women freshly diagnosed. In contrast. numbers of CD4 +, CD3 +, CD19 + lymphocytes and of total lymphocytes in peripheral blood were significantly lower in women studied during follow-up. The results suggest that high neopterin levels in tumor patients indicate activation of early steps of cellular immune mechanisms.


1987 ◽  
Vol 114 (4) ◽  
pp. 559-564 ◽  
Author(s):  
C. Ferrari ◽  
A. Paracchi ◽  
E. Parisio ◽  
F. Codecasa ◽  
M. Mucci ◽  
...  

Abstract. Serum total and free T4 and T3, thyroxinebinding globulin (TBG) and TSH, basal and 20, 30 and 60 min after TRH (200 μg, iv), were evaluated in 125 hypothyroid patients (38 with severe, 23 with mild, and 64 with subclinical hypothyroidism), in 35 euthyroid subjects with autoimmune thyroiditis, and in 51 healthy controls. T4/TBG and T3/TBG ratios were also calculated. A significant decrease in all indices of thyroid function except for T3 occurred simultaneously with a significant increase in basal and TRH-stimulated TSH levels from healthy subjects to subclinical hypothyroids, from subclinical to mild and from mild to severe hypothyroids; euthyroid patients with autoimmune thyroiditis did not differ from healthy subjects. All severe hypothyroid patients had low T4 as well as free T4 (FT4), free T3 (FT3), T4/TBG and T3/TBG ratios, but among mild and subclinical hypothyroids direct determination of FT4 and FT3 proved to be a better index of thyroid function than determination of T4 and T3 even after correction for TBG levels. FT4 was the most commonly abnormal index (19 of 23 subjects with mild and 14 of 64 with subclinical disease). Regression analysis showed that FT4, T4/TBG ratio, T4, and FT3 had a significant inverse correlation with TSH in hypothyroid patients. Discriminant analysis showed that among the thyroid parameters, FT4 is the variable which discriminates best between control subjects and the 3 groups of hypothyroid patients. These data extend previous reports and in a large series of patients confirm the biological meaning and the clinical value of direct measurement of serum free thyroid hormones in hypothyroidism. Nevertheless, the finding that both FT4 and FT3 are in the normal range in some patients with mild and in most with subclinical hypothyroidism indicates that increased TSH secretion remains the most sensitive index of thyroid failure.


1984 ◽  
Vol 105 (3) ◽  
pp. 324-329 ◽  
Author(s):  
T. Bjøro ◽  
P. I. Gaarder ◽  
E. B. Smeland ◽  
L. Kornstad

Abstract. In sera from 1643 randomly selected blood donors examined in 1979 thyroglobulin antibodies (TGA) were found in 3.4% and thyroid microsomal antibodies (TMA) in 7.0%. TMA, but not TGA, showed significant sex and age relationships. Eighty-two donors with TMA titres ≥ 1600 and/or TGA titres ≥ 128 were available for a follow-up study in 1982. In 69 of these with TMA there was a significantly increased incidence of pathological thyroid function-test values (T4, T3 and TSH) as compared to age- and sexmatched donors without thyroid antibodies. In this group 9 individuals had overt and three latent hypothyroidism, two individuals were found with symptomless autoimmune thyroiditis and one with a non-toxic nodular goitre. Only 2 of these had been diagnosed before 1982, and none recognized before 1979. In addition, the group contained 9 individuals who had been treated because of hyperthyroidism, all except one before 1979. The likelihood of detecting a previously unrecognized hypothyroidism increased with increasing TMA titre. In contrast, the 24 donors with TGA did not show an increased frequency of pathological thyroid function-test- values in 1982.


2021 ◽  
Vol 10 (10) ◽  
pp. 2213
Author(s):  
Alessia Scatena ◽  
Pasquale Petruzzi ◽  
Filippo Maioli ◽  
Francesca Lucaroni ◽  
Cristina Ambrosone ◽  
...  

Peripheral blood mononuclear cells (PBMNCs) are reported to prevent major amputation and healing in no-option critical limb ischemia (NO-CLI). The aim of this study is to evaluate PBMNC treatment in comparison to standard treatment in NO-CLI patients with diabetic foot ulcers (DFUs). The study included 76 NO-CLI patients admitted to our centers because of CLI with DFUs. All patients were treated with the same standard care (control group), but 38 patients were also treated with autologous PBMNC implants. Major amputations, overall mortality, and number of healed patients were evaluated as the primary endpoint. Only 4 out 38 amputations (10.5%) were observed in the PBMNC group, while 15 out of 38 amputations (39.5%) were recorded in the control group (p = 0.0037). The Kaplan–Meier curves and the log-rank test results showed a significantly lower amputation rate in the PBMNCs group vs. the control group (p = 0.000). At two years follow-up, nearly 80% of the PBMNCs group was still alive vs. only 20% of the control group (p = 0.000). In the PBMNC group, 33 patients healed (86.6%) while only one patient healed in the control group (p = 0.000). PBMNCs showed a positive clinical outcome at two years follow-up in patients with DFUs and NO-CLI, significantly reducing the amputation rate and improving survival and wound healing. According to our study results, intramuscular and peri-lesional injection of autologous PBMNCs could prevent amputations in NO-CLI diabetic patients.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lin Yan ◽  
Mingbo Zhang ◽  
Fang Xie ◽  
Jun Ma ◽  
Jing Xiao ◽  
...  

Abstract Background Radiofrequency ablation (RFA) is recommended for the treatment of benign thyroid nodules. However, data on the clinical role of RFA for benign thyroid nodules in patients with history of thyroid lobectomy are insufficient. The purpose of this study was to evaluate the efficacy and safety of radiofrequency ablation (RFA) for benign thyroid nodules in patients who had previously undergoing thyroid lobectomy. Methods From May 2015 to October 2018, a total of 20 patients (19 females, 1 male, mean age 49.50 ± 14.26 years, range 22–74 years) with 20 benign thyroid nodules (mean volume 15.04 ± 21.17 ml, range 0.40–69.67 ml) who had undergone previous thyroid lobectomy were included in this retrospective study. Patients were followed up at 3, 6, 12 months after RFA and every 12 months thereafter by ultrasound, clinical evaluation and thyroid function. Volume, volume reduction rate (VRR), symptom score and cosmetic score were evaluated. Results During the mean follow-up time of 21.24 ± 16.41 months, the mean nodule volume decreased significantly from 15.04 ± 21.17 ml to 1.29 ± 1.17 ml (P = 0.018) with a mean VRR of 85.41 ± 12.17%. Therapeutic success was achieved in a single session for all thyroid nodules. The symptom score (P = 0.001) and cosmetic score (P = 0.001) were both significantly reduced at the last follow-up. The levels of free triiodothyronine (fT3), free thyroxine (fT4) and thyroid stimulating hormone were not significantly different at the last follow-up from those prior to treatment (all P > 0.05). No life-threatening complications or sequelae occurred after RFA. Conclusions As a minimally invasive modality, RFA was a safe, effective, and thyroid function-preserving option for patients with symptomatic benign thyroid nodules after a previous lobectomy.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 681.1-681
Author(s):  
L. Garzanova ◽  
L. P. Ananyeva ◽  
O. Koneva ◽  
O. Desinova ◽  
O. Ovsyannikova ◽  
...  

Background:Rituximab (RTX) is a new option in the treatment of systemic sclerosis (SSc) [1]. There is not enough data on changes in the level of autoantibodies and their clinical significance during RTM therapy. There are only a few reports on the higher efficiency of RTX in patients (pts) with SSc positive for anti-topoisomerase-1 antibodies (a-Topo-1), therefore the study of this issue might be interested.Objectives:To compare clinical parameters and B-lymphocytes (B-lymph) level in SSc pts depending on the presence or absence of a-Topo-1 during RTX therapy with prospective long-term follow-up.Methods:This study included 88 pts with SSc. The mean follow-up period was 26,3±10,7 months. The mean age was 47years (17-71), female-73 pts (83%), the diffuse cutaneous subset of the disease had 50 pts (57%). Symptoms of the interstitial lung disease (ILD) were observed in 70 pts (80%). The mean disease duration was 5,9±4,8 years. The cumulative mean dose of RTX was 2,9±1,1 grams. All patients received prednisone at a dose of 11,7±4,4 mg, immunosuppressants received 42% of them. There were 63 pts positive for a-Topo-1 and 25 pts - negative. The pts of the compared groups did not differ in the main demographic and clinical parameters, excepting lung involvement. In a-Topo-1 positive group 55 (87%) pts had ILD and only 15 (60%) – in a-Topo-1-negative group (p=0,02). The results at baseline and at the end of the follow up are presented in the form of mean values and changes in parameters (delta).Results:Considering the entire cohort, an improvement of almost all outcome parameters was found. When a-Topo-1 positive and a-Topo-1-negative pts were analyzed separately, we observed a significantly higher decrease in the activity score, depletion of B-lymph, an increase in forced vital capacity (FVC) and diffusion capacity for carbon monoxide (DLCO) in a-Topo-1 positive group of pts (table 1).Table 1.Changes of the main outcome parameters depending on the presence of a-Topo-1 on RTX therapy.Parametersa-Topo-1positive ptsa-Topo-1negative ptsPDelta Activity score (EScSG-AI)1,790,90,001Delta Rodnan skin score (mRSS)4,95,2NSDelta B-lymphocytes (absolute count)0,2120,1930,001Delta FVC*, %8,646,460,001Delta DLCO**, %2,860,0320,001*FVC - forced vital capacity % predicted, **DLCO - diffusion capacity for carbon monoxide % predictedThe a-Тopo-1 level decreased from 174,2±50,1 to 148,1±66,1 units/ml (p=0,0009). In this group, a-Тopo-1 became negative in 5 pts (7,9%). The disappearance of a-Topo-1 positivity was accompanied by a more pronounced decrease in mRSS (delta mRSS=7,4) and a higher depletion of B-lymph. There was a higher cumulative dose of RTX (4±1,4grams) in this 5 pts compared with the pts who sustained a-Topo-1 positivity. There was a moderate negative statistically significant correlation between the a-Topo-1 and the total dose of RTX (r=-0,298, p=0,017). A moderate negative statistically significant correlation was found between the a-Topo-1 and FVC (r=-0,322, p=0,009).Conclusion:In our study, the a-Topo-1 level significantly decreased during RTX therapy in Russian pts. The decrease in a-Topo-1 titers correlated with the total dose of RTX and was accompanied by a decrease in mRSS, disease activity index and an increase in FVC and DLCO. A higher efficacy of RTX in the a-Topo-1 positive group with prevalence of ILD was revealed, therefore a-Topo-1 positivity could be considered as a predictor of a better response to RTX therapy.References:[1]Jordan S, et al. Effects and safety of rituximab in systemic sclerosis: an analysis from the European Scleroderma Trial and Research (EUSTAR) group. Ann Rheum Dis.2015;74:1188–94.Doi:10.1136/annrheumdis-2013-204522.[2]Ebata S, Yoshizaki A, et.al. Rituximab therapy is more effective than cyclophosphamide therapy for Japanese patients with anti-topoisomerase I-positive systemic sclerosis-associated interstitial lung disease. J Dermatol.2019.Nov;46(11):1006-1013.doi:10.1111/1346-8138.15079.Disclosure of Interests:None declared


Sign in / Sign up

Export Citation Format

Share Document