TY  - JOUR
AU  - Sarić-Matutinović, Marija
AU  - Diana, Tanja
AU  - Nedeljković-Beleslin, Biljana
AU  - Ćirić, Jasmina
AU  - Žarković, Miloš
AU  - Perović Blagojević, Iva
AU  - Kahaly, George
AU  - Ignjatović, Svetlana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4091
AB  - Background: Thyrotropin receptor autoantibodies (TSH-R-Ab) are indispensable biomarkers in the laboratory assessment of thyroid-associated orbitopathy (TAO). Clinical sensitivity of three different assays for TSH-R-Ab determination was evaluated in patients with TAO.

Methods: 87 consecutive TAO patients were enrolled and their serum samples analyzed in parallel with three assays. An ECLIA competitive binding and a chemiluminescent bridge immunoassay were used to measure total and bind-ing TSH-R-Ab concentration, while their functional activity was determined using a stimulatory TSH-R-Ab (TSAb) cell-based bioassay.

Results: Compared to the two binding assays (ECLIA p<0.001, bridge p=0.003), the TSAb bioassay was more sensitive pertaining to the positive detection of TSH-R-Ab in TAO patients. No difference (p=0.057) was noted between the ECLIA and bridge assays regarding sensitivity rate. All patients with active and/or moderate-to-severe TAO tested positive in the TSAb bioassay (100% and 100%, respectively), while the positivity rates for bridge and ECLIA binding assays were 89.7% and 82.1% for active TAO, and 90.2% and 86.3% for severe TAO, respectively. Negative predictive values of the bioassay, bridge, and ECLIA assays were 100%, 75%, and 71%, respectively for active TAO, and 100%, 86%, and 71%, respectively for moderate-to-severe TAO. The superiority of the bioassay was most prominent in euthyroid (ET) TAO. Positivity rates of the TSAb bioassay, bridge and ECLIA binding assays were 89.6%, 75%, and 64.6%, respectively for inactive TAO; 86.1%, 69.4%, and 52.8%, respectively for mild TAO; 87.5%, 62.5%, and 12.5%, respectively for euthyroid TAO. The bridge assay correlated better with the ECLIA binding assay (r=0.893, p<0.001), compared to the bioassay (r=0.669, p<0.001).

Conclusions: In patients with TAO of various activity and severity, the TSAb bioassay demonstrates a superior clinical performance compared to both ECLIA and bridge binding assays.
AB  - Uvod: Autoantitela na receptore za tireostimulišući hormon (TSH-R-Ab) su nezamenljivi biomarkeri u laboratorijskoj proceni orbitopatije udru'ene sa štitnom žlezdom (TAO). U radu je procenjena klinička osetljivost tri različita testa za određivanje TSH-R-Ab kod pacijenata sa TAO. Metode: U studiju je ključeno 87 uzastopnih pacijenata sa TAO i njihovi uzorci seruma su analizirani paralelno sa tri testa. Za merenje ukupne i vezujuće koncentracije TSH-RAb korišćeni su ECLIA imunohemijski test kompetitivnog vezivanja i hemiluminiscentni imunohemijski "sendvič" test, dok je njihova funkcionalna aktivnost određena pomoću ćelijskog biološkog testa (bioeseja) za određivanje stimulatornih TSH-R-Ab (TSAb). Rezultati: U poređenju sa dva imunohemijska testa vezivanja (ECLIA P<0,001, "sendvič test" P=0,003), TSAb bioesej se pokazao najosetljivijim u pogledu pozitivne detekcije TSH-RAb kod TAO pacijenata. Nikakva razlika nije detektovana (P=0,057) između ECLIA i "sendvič" testa u pogledu stope osetljivosti. TSAb bioesej je bio pozitivan kod svih pacijenata sa aktivnom i/ili umerenom do teškom TAO (redom 100% i 100%), dok su stope pozitivnosti za sendvič i ECLIA imunohemijski test bile 89,7% i 82,1% za aktivnu TAO, i 90,2% i 86,3% za tešku TAO, redom. Negativne prediktivne vrednosti bioeseja, "sendvič" i ECLIA testova bile su redom 100%, 75% i 71%, za aktivnu TAO, odnosno 100%, 86% i 71%, redom za umerenu do tešku TAO. Superiornost biološke analize bila je najistaknutija kod eutiroidnog oblika (ET) TAO. Stope pozitivnosti TSAb bioeseja, "sendvič" i ECLIA testova vezivanja bile su redom 89,6%, 75% i 64,6%, za neaktivnu TAO; 86,1%, 69,4% i 52,8% za blagu TAO; 87,5%, 62,5% i 12,5% za eutiroidni TAO. "Sendvič" imunohemijski test je bio u boljoj korelaciji sa ECLIA testom kompetitivnog vezivanja (r=0,893, P<0,001), u poređenju sa bioesejom (r=0,669, P<0,001). Zaključak: Kod pacijenata sa TAO različite aktivnosti i težine TSAb bioesej pokazuje superiorne kliničke performanse u poređenju sa obe vrste imunohemijskih testova vezivanja (ECLIA i "sendvič test").
PB  - Society of Medical Biochemists of Serbia
T2  - Journal of Medical Biochemistry
T1  - Sensitivity of three thyrotropin receptor antibody assays in thyroid-associated orbitopathy
T1  - Osetljivost tri testa za određivanje antitela na receptor za tireostimulišući hormon kod pacijenata sa orbitopatijom udruženom sa štitnom žlezdom
VL  - 41
IS  - 2
SP  - 211
EP  - 220
DO  - 10.5937/jomb0-34718
ER  - 

@article{
author = "Sarić-Matutinović, Marija and Diana, Tanja and Nedeljković-Beleslin, Biljana and Ćirić, Jasmina and Žarković, Miloš and Perović Blagojević, Iva and Kahaly, George and Ignjatović, Svetlana",
year = "2022",
abstract = "Background: Thyrotropin receptor autoantibodies (TSH-R-Ab) are indispensable biomarkers in the laboratory assessment of thyroid-associated orbitopathy (TAO). Clinical sensitivity of three different assays for TSH-R-Ab determination was evaluated in patients with TAO.

Methods: 87 consecutive TAO patients were enrolled and their serum samples analyzed in parallel with three assays. An ECLIA competitive binding and a chemiluminescent bridge immunoassay were used to measure total and bind-ing TSH-R-Ab concentration, while their functional activity was determined using a stimulatory TSH-R-Ab (TSAb) cell-based bioassay.

Results: Compared to the two binding assays (ECLIA p<0.001, bridge p=0.003), the TSAb bioassay was more sensitive pertaining to the positive detection of TSH-R-Ab in TAO patients. No difference (p=0.057) was noted between the ECLIA and bridge assays regarding sensitivity rate. All patients with active and/or moderate-to-severe TAO tested positive in the TSAb bioassay (100% and 100%, respectively), while the positivity rates for bridge and ECLIA binding assays were 89.7% and 82.1% for active TAO, and 90.2% and 86.3% for severe TAO, respectively. Negative predictive values of the bioassay, bridge, and ECLIA assays were 100%, 75%, and 71%, respectively for active TAO, and 100%, 86%, and 71%, respectively for moderate-to-severe TAO. The superiority of the bioassay was most prominent in euthyroid (ET) TAO. Positivity rates of the TSAb bioassay, bridge and ECLIA binding assays were 89.6%, 75%, and 64.6%, respectively for inactive TAO; 86.1%, 69.4%, and 52.8%, respectively for mild TAO; 87.5%, 62.5%, and 12.5%, respectively for euthyroid TAO. The bridge assay correlated better with the ECLIA binding assay (r=0.893, p<0.001), compared to the bioassay (r=0.669, p<0.001).

Conclusions: In patients with TAO of various activity and severity, the TSAb bioassay demonstrates a superior clinical performance compared to both ECLIA and bridge binding assays., Uvod: Autoantitela na receptore za tireostimulišući hormon (TSH-R-Ab) su nezamenljivi biomarkeri u laboratorijskoj proceni orbitopatije udru'ene sa štitnom žlezdom (TAO). U radu je procenjena klinička osetljivost tri različita testa za određivanje TSH-R-Ab kod pacijenata sa TAO. Metode: U studiju je ključeno 87 uzastopnih pacijenata sa TAO i njihovi uzorci seruma su analizirani paralelno sa tri testa. Za merenje ukupne i vezujuće koncentracije TSH-RAb korišćeni su ECLIA imunohemijski test kompetitivnog vezivanja i hemiluminiscentni imunohemijski "sendvič" test, dok je njihova funkcionalna aktivnost određena pomoću ćelijskog biološkog testa (bioeseja) za određivanje stimulatornih TSH-R-Ab (TSAb). Rezultati: U poređenju sa dva imunohemijska testa vezivanja (ECLIA P<0,001, "sendvič test" P=0,003), TSAb bioesej se pokazao najosetljivijim u pogledu pozitivne detekcije TSH-RAb kod TAO pacijenata. Nikakva razlika nije detektovana (P=0,057) između ECLIA i "sendvič" testa u pogledu stope osetljivosti. TSAb bioesej je bio pozitivan kod svih pacijenata sa aktivnom i/ili umerenom do teškom TAO (redom 100% i 100%), dok su stope pozitivnosti za sendvič i ECLIA imunohemijski test bile 89,7% i 82,1% za aktivnu TAO, i 90,2% i 86,3% za tešku TAO, redom. Negativne prediktivne vrednosti bioeseja, "sendvič" i ECLIA testova bile su redom 100%, 75% i 71%, za aktivnu TAO, odnosno 100%, 86% i 71%, redom za umerenu do tešku TAO. Superiornost biološke analize bila je najistaknutija kod eutiroidnog oblika (ET) TAO. Stope pozitivnosti TSAb bioeseja, "sendvič" i ECLIA testova vezivanja bile su redom 89,6%, 75% i 64,6%, za neaktivnu TAO; 86,1%, 69,4% i 52,8% za blagu TAO; 87,5%, 62,5% i 12,5% za eutiroidni TAO. "Sendvič" imunohemijski test je bio u boljoj korelaciji sa ECLIA testom kompetitivnog vezivanja (r=0,893, P<0,001), u poređenju sa bioesejom (r=0,669, P<0,001). Zaključak: Kod pacijenata sa TAO različite aktivnosti i težine TSAb bioesej pokazuje superiorne kliničke performanse u poređenju sa obe vrste imunohemijskih testova vezivanja (ECLIA i "sendvič test").",
publisher = "Society of Medical Biochemists of Serbia",
journal = "Journal of Medical Biochemistry",
title = "Sensitivity of three thyrotropin receptor antibody assays in thyroid-associated orbitopathy, Osetljivost tri testa za određivanje antitela na receptor za tireostimulišući hormon kod pacijenata sa orbitopatijom udruženom sa štitnom žlezdom",
volume = "41",
number = "2",
pages = "211-220",
doi = "10.5937/jomb0-34718"
}

Sarić-Matutinović, M., Diana, T., Nedeljković-Beleslin, B., Ćirić, J., Žarković, M., Perović Blagojević, I., Kahaly, G.,& Ignjatović, S.. (2022). Sensitivity of three thyrotropin receptor antibody assays in thyroid-associated orbitopathy. in Journal of Medical Biochemistry
Society of Medical Biochemists of Serbia., 41(2), 211-220.
https://doi.org/10.5937/jomb0-34718

Sarić-Matutinović M, Diana T, Nedeljković-Beleslin B, Ćirić J, Žarković M, Perović Blagojević I, Kahaly G, Ignjatović S. Sensitivity of three thyrotropin receptor antibody assays in thyroid-associated orbitopathy. in Journal of Medical Biochemistry. 2022;41(2):211-220.
doi:10.5937/jomb0-34718 .

Sarić-Matutinović, Marija, Diana, Tanja, Nedeljković-Beleslin, Biljana, Ćirić, Jasmina, Žarković, Miloš, Perović Blagojević, Iva, Kahaly, George, Ignjatović, Svetlana, "Sensitivity of three thyrotropin receptor antibody assays in thyroid-associated orbitopathy" in Journal of Medical Biochemistry, 41, no. 2 (2022):211-220,
https://doi.org/10.5937/jomb0-34718 . .

TY  - JOUR
AU  - Bećarević, Mirjana
AU  - Sarić-Matutinović, Marija
AU  - Žarković, Miloš
AU  - Nedeljković-Beleslin, Biljana
AU  - Ćirić, Jasmina
AU  - Ignjatović, Svetlana
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3909
AB  - Purpose: Graves’ orbitopathy (GO) is an inflammatory autoimmune disorder of the orbit and while the antiphospholipid antibodies (aPL) Abs were associated with the markers of inflammation in the antiphospholipid syndrome (APS), there is no literature that investigate the presence of aPL Abs in GO. We analyzed the prevalence of aPL Abs and the differences between aPL (+) and aPL (−) subgroups of GO patients. Methods: Study included consecutive patients with GO (66 with Graves’ (GD), 10 with Hashimoto (HD), and 8 were euthyroid). Anticardiolipin (aCL) and anti-beta 2glycoprotein I (aβ2gpI) Abs were measured by ELISA. Results: aPL Abs were present in 9/84 (10.71%) patients. The IgM aβ2gpI Abs were present in 8/66 and in 1/10 patients with GD and HD. The IgG aCL Abs were present in one GD patient, and IgM aCL were present in 3/66 GD and in 1/10 patients with HD. In GD group, anti-Tg Abs were in positive correlation with aβ2gpI IgG (p = 0.000) and with anti-TPO Abs (p = 0.016). In HD group, anti-Tg Abs were in positive correlation with IgM aCL (p = 0.042), while anti-TPO Abs were in positive correlation with aβ2gpI IgM (p = 0.014). Conclusion: This study is the first report of the aPL Abs presence in GO patients. The anti-thyroid Abs were linked to aPL suggesting that their presence is not the sole consequence of hyperstimulation of autoreactive B-lymphocytes. Larger studies are necessary to confirm potential cause-effect relations. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PB  - Springer
T2  - Endocrine
T1  - Antiphospholipid antibodies in patients with Graves’orbitopathy:preliminary data
DO  - 10.1007/s12020-021-02769-z
ER  - 

@article{
author = "Bećarević, Mirjana and Sarić-Matutinović, Marija and Žarković, Miloš and Nedeljković-Beleslin, Biljana and Ćirić, Jasmina and Ignjatović, Svetlana",
year = "2021",
abstract = "Purpose: Graves’ orbitopathy (GO) is an inflammatory autoimmune disorder of the orbit and while the antiphospholipid antibodies (aPL) Abs were associated with the markers of inflammation in the antiphospholipid syndrome (APS), there is no literature that investigate the presence of aPL Abs in GO. We analyzed the prevalence of aPL Abs and the differences between aPL (+) and aPL (−) subgroups of GO patients. Methods: Study included consecutive patients with GO (66 with Graves’ (GD), 10 with Hashimoto (HD), and 8 were euthyroid). Anticardiolipin (aCL) and anti-beta 2glycoprotein I (aβ2gpI) Abs were measured by ELISA. Results: aPL Abs were present in 9/84 (10.71%) patients. The IgM aβ2gpI Abs were present in 8/66 and in 1/10 patients with GD and HD. The IgG aCL Abs were present in one GD patient, and IgM aCL were present in 3/66 GD and in 1/10 patients with HD. In GD group, anti-Tg Abs were in positive correlation with aβ2gpI IgG (p = 0.000) and with anti-TPO Abs (p = 0.016). In HD group, anti-Tg Abs were in positive correlation with IgM aCL (p = 0.042), while anti-TPO Abs were in positive correlation with aβ2gpI IgM (p = 0.014). Conclusion: This study is the first report of the aPL Abs presence in GO patients. The anti-thyroid Abs were linked to aPL suggesting that their presence is not the sole consequence of hyperstimulation of autoreactive B-lymphocytes. Larger studies are necessary to confirm potential cause-effect relations. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.",
publisher = "Springer",
journal = "Endocrine",
title = "Antiphospholipid antibodies in patients with Graves’orbitopathy:preliminary data",
doi = "10.1007/s12020-021-02769-z"
}

Bećarević, M., Sarić-Matutinović, M., Žarković, M., Nedeljković-Beleslin, B., Ćirić, J.,& Ignjatović, S.. (2021). Antiphospholipid antibodies in patients with Graves’orbitopathy:preliminary data. in Endocrine
Springer..
https://doi.org/10.1007/s12020-021-02769-z

Bećarević M, Sarić-Matutinović M, Žarković M, Nedeljković-Beleslin B, Ćirić J, Ignjatović S. Antiphospholipid antibodies in patients with Graves’orbitopathy:preliminary data. in Endocrine. 2021;.
doi:10.1007/s12020-021-02769-z .

Bećarević, Mirjana, Sarić-Matutinović, Marija, Žarković, Miloš, Nedeljković-Beleslin, Biljana, Ćirić, Jasmina, Ignjatović, Svetlana, "Antiphospholipid antibodies in patients with Graves’orbitopathy:preliminary data" in Endocrine (2021),
https://doi.org/10.1007/s12020-021-02769-z . .

TY  - JOUR
AU  - Žarković, Miloš
AU  - Ignjatović, Svetlana
AU  - Dajak, Marijana
AU  - Ćirić, Jasmina
AU  - Beleslin, Biljana
AU  - Savić, Slavica
AU  - Stojković, Mirjana
AU  - Bulat, Petar
AU  - Trbojević, Bozo
PY  - 2008
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1026
AB  - Objective: Interleukin 6(IL6) has the ability to influence each level of the hypothalamo-pituitary-adrenocortical (HPA) axis. The aim of the study was to test whether IL6 concentration correlates with the adrenal cortex response to ACTH in healthy humans. We postulated that higher basal IL6 concentration would be associated with the higher cortisol response to the stimulation. Design and methods: Basal IL6 concentration was measured and a low dose (1 mu g) ACTH test was performed to assess cortisol response. apparently healthy Subjects (11 male. 16 female. mean age 31.1 years. age range 22-47 years) were included in the study. Results: Data are presented as mean +/- S.E.M. Basal IL6 level was 0.84 +/- 0.10 pg/ml, Basal cortisol was 351.9 +/- 18.3. nmol/l. Maximal cortisol during synacthen test was 653.0 +/- 20.6 nmol/l. Maximal cortisol increment was 301.1 +/- 20.0 nmol/l. IL6 concentration was not correlated with basal or maximal cortisol concentration. but correlated significantly with cortisol increment (r=0.63. 95%. confidence interval) 0.42-0.83). Conclusions: In our study. We found that higher basal IL6 concentration is associated with the higher cortisol response to ACTH stimulation. Based on previous research and our data, IL6, even in low concentrations and under physiologic conditions, modulates adrenal cortex responsivity to ACTH. Therefore. it seems that immune modulation of HPA axis is also present under physiologic and not only pathologic conditions.
PB  - Bioscientifica Ltd, Bristol
T2  - European Journal of Endocrinology
T1  - Cortisol response to ACTH stimulation correlates with blood interleukin 6 concentration in healthy humans
VL  - 159
IS  - 5
SP  - 649
EP  - 652
DO  - 10.1530/EJE-08-0544
ER  - 

@article{
author = "Žarković, Miloš and Ignjatović, Svetlana and Dajak, Marijana and Ćirić, Jasmina and Beleslin, Biljana and Savić, Slavica and Stojković, Mirjana and Bulat, Petar and Trbojević, Bozo",
year = "2008",
abstract = "Objective: Interleukin 6(IL6) has the ability to influence each level of the hypothalamo-pituitary-adrenocortical (HPA) axis. The aim of the study was to test whether IL6 concentration correlates with the adrenal cortex response to ACTH in healthy humans. We postulated that higher basal IL6 concentration would be associated with the higher cortisol response to the stimulation. Design and methods: Basal IL6 concentration was measured and a low dose (1 mu g) ACTH test was performed to assess cortisol response. apparently healthy Subjects (11 male. 16 female. mean age 31.1 years. age range 22-47 years) were included in the study. Results: Data are presented as mean +/- S.E.M. Basal IL6 level was 0.84 +/- 0.10 pg/ml, Basal cortisol was 351.9 +/- 18.3. nmol/l. Maximal cortisol during synacthen test was 653.0 +/- 20.6 nmol/l. Maximal cortisol increment was 301.1 +/- 20.0 nmol/l. IL6 concentration was not correlated with basal or maximal cortisol concentration. but correlated significantly with cortisol increment (r=0.63. 95%. confidence interval) 0.42-0.83). Conclusions: In our study. We found that higher basal IL6 concentration is associated with the higher cortisol response to ACTH stimulation. Based on previous research and our data, IL6, even in low concentrations and under physiologic conditions, modulates adrenal cortex responsivity to ACTH. Therefore. it seems that immune modulation of HPA axis is also present under physiologic and not only pathologic conditions.",
publisher = "Bioscientifica Ltd, Bristol",
journal = "European Journal of Endocrinology",
title = "Cortisol response to ACTH stimulation correlates with blood interleukin 6 concentration in healthy humans",
volume = "159",
number = "5",
pages = "649-652",
doi = "10.1530/EJE-08-0544"
}

Žarković, M., Ignjatović, S., Dajak, M., Ćirić, J., Beleslin, B., Savić, S., Stojković, M., Bulat, P.,& Trbojević, B.. (2008). Cortisol response to ACTH stimulation correlates with blood interleukin 6 concentration in healthy humans. in European Journal of Endocrinology
Bioscientifica Ltd, Bristol., 159(5), 649-652.
https://doi.org/10.1530/EJE-08-0544

Žarković M, Ignjatović S, Dajak M, Ćirić J, Beleslin B, Savić S, Stojković M, Bulat P, Trbojević B. Cortisol response to ACTH stimulation correlates with blood interleukin 6 concentration in healthy humans. in European Journal of Endocrinology. 2008;159(5):649-652.
doi:10.1530/EJE-08-0544 .

Žarković, Miloš, Ignjatović, Svetlana, Dajak, Marijana, Ćirić, Jasmina, Beleslin, Biljana, Savić, Slavica, Stojković, Mirjana, Bulat, Petar, Trbojević, Bozo, "Cortisol response to ACTH stimulation correlates with blood interleukin 6 concentration in healthy humans" in European Journal of Endocrinology, 159, no. 5 (2008):649-652,
https://doi.org/10.1530/EJE-08-0544 . .