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Clinical Significance of IgG4 Serum Concentration in Graves’ Disease

Michal Olejarz
Michal Olejarz
, 
Ewelina Szczepanek-Parulska
Ewelina Szczepanek-Parulska
, 
Aleksandra Krygier
Aleksandra Krygier
, 
Elzbieta Wrotkowska
Elzbieta Wrotkowska
, 
Nadia Sawicka-Gutaj
Nadia Sawicka-Gutaj
 y 
Marek Ruchala
Marek Ruchala
   | 20 jul 2024
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Publicado en línea: 20 jul 2024
Páginas: -
Recibido: 21 mar 2024
Aceptado: 20 jun 2024
DOI: https://doi.org/10.2478/aite-2024-0015
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© 2024 Michal Olejarz et al., published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Fig 1.

Flowchart displaying the composition of the studied group. GD, Graves’ disease; GO, Graves’ orbitopathy.
Flowchart displaying the composition of the studied group. GD, Graves’ disease; GO, Graves’ orbitopathy.

Fig 2.

Boxplots comparing IgG4 serum concentration between GD without orbitopathy, moderate-to-severe GO, and the control group. GD, Graves’ disease; GO, Graves’ orbitopathy; IgG4, Immunoglobulin G4.
Boxplots comparing IgG4 serum concentration between GD without orbitopathy, moderate-to-severe GO, and the control group. GD, Graves’ disease; GO, Graves’ orbitopathy; IgG4, Immunoglobulin G4.

Fig 3.

The ROC curve of IgG4 as a diagnostic tool for diagnosing moderate-to-severe GO. The optimal cut-off value determined by the highest Youden index was 49 mg/dL. At this cut-off value, the AUC was 0.851 (P < 0.001), negative predictive value was 100%, positive predictive value 48%, sensitivity 100%, and specificity 73%. AUC, area under the curve; GO, Graves’ orbitopathy; IgG4, Immunoglobulin G4; ROC, receiver operating characteristic.
The ROC curve of IgG4 as a diagnostic tool for diagnosing moderate-to-severe GO. The optimal cut-off value determined by the highest Youden index was 49 mg/dL. At this cut-off value, the AUC was 0.851 (P < 0.001), negative predictive value was 100%, positive predictive value 48%, sensitivity 100%, and specificity 73%. AUC, area under the curve; GO, Graves’ orbitopathy; IgG4, Immunoglobulin G4; ROC, receiver operating characteristic.

Comparison of IgG, IgG4, and other biochemical features between hyperthyroid and euthyroid patients with GD

Hyperthyroid GD (N = 32) Euthyroid GD (N = 28) P-value
IgG4 (mg/dL) 33 (23.78; 58.3) 52.4 (29.45; 95.6) 0.061
Total IgG (g/L) 11.72 (10.88; 13.09) 10.65 (9.77; 12.34) 0.098
TSH (μU/mL) 0.01 (0.01; 0.01) 1.55 (0.81; 2.25) <0.001
fT3 (pmol/L) 25.72 (17.35; 31.95) 4.72 (4.44; 5.23) <0.001
fT4 (pmol/L) 48.91 (38.08; 79.9) 15.14 (13.09; 16.01) <0.001
TRAb (IU/I) 13.23 (6.43; 23.31) 2.09 (0.9; 3.98) <0.001
TPOAb (IU/mL) 246 (59.75; 410.75) 63 (27; 147.25) 0.004
TgAb (IU/mL) 271 (35.25; 525.25) 20.5 (10.75; 164) 0.006
CRP (mg/dL) 1.15 (0.5; 2.53) 1.05 (0.48; 2.13) 0.953
Moderate-to-severe GO (% of patients) 9.38 32.14 0.050

Correlations of selected biochemical, hormonal, anthropometric, and ultrasound parameters with serum IgG4 and IgG levels

IgG4 Total IgG
IgG4 – ρ = 0.072, P = 0.586
Total IgG ρ = 0.072, P = 0.586 –
Age (years) ρ = (−)0.085, P = 0.517 R = (−)0.239, P = 0.066
CRP ρ = (−)0.084, P = 0.523 ρ = (−)0.070, P = 0.594
TSH ρ = 0.236, P = 0.070 ρ = (−)0.149, P = 0.258
fT3 ρ = (−)0.197, P = 0.131 ρ = 0.353, P = 0.006
fT4 ρ = (−)0.260, P = 0.045 ρ = 0.387, P = 0.002
TRAb ρ = (−)0.270, P = 0.037 ρ = −0.032, P = 0.803
TPOAb ρ = 0.052, P = 0.695 ρ = 0.130, P = 0.324
TgAb ρ = 0.202, P = 0.685 ρ = 0.202, P = 0.122
Creatinine ρ = 0.117, P = 0.373 ρ = 0.062, P = 0.637
ALT ρ = (−)0.167, P = 0.202 ρ = 0.033, P = 0.800
AST ρ = (−)0.047, P = 0.724 ρ = 0.103, P = 0.433
WBC ρ = (−)0.0512, P = 0.697 R = (−)0.106, P = 0.421
RBC ρ = 0.0852, P = 0.517 R = 0.219, P = 0.093
Hemoglobin ρ = 0.033, P = 0.800 R = (−)0.133, P = 0.309
PLT ρ = (−)0.033, R = 0.800 R = 0.142, P = 0.278
Thyroid volume ρ = (−)0.233, P = 0.087 ρ = 0.145, P = 0.290
Intrathyroidal blood flow ρ = (−)0.075, P = 0.594 ρ = 0.073, P = 0.603
Thyroid echogenicity ρ = 0.077, P = 0.578 ρ = (−)0.153, P = 0.266
Number of thyroid nodules ρ = (−)0.263, P = 0.054 ρ = (−)0.322, P = 0.117

Comparison of clinical, biochemical, and ultrasonographic features between high IgG4 and normal IgG4 GD

GD patients with IgG4 serum concentration within normal range (N = 54) GD patients with high IgG4 serum concentration (N = 6) P-value
IgG4 (mg/dL) 33.9 (25.73; 67.8) 159.5 (143.78; 174.93) <0.001
Total IgG (g/L) 11.25 (10.31; 12.4) 11.39 (10.69; 14.58) 0.411
Age (years) 39.96 ± 13.44 38.83 ± 11.84 0.844
Gender (% of males) 14 (25.93%) 1 (16.67%) 1
TSH (μIU/mL) 0.01 (0.01; 1.33) 1.54 (0.34; 1.94) 0.095
fT3 (pmol/L) 10.78 (4.74; 26.2) 6.06 (4.93; 6.76) 0.498
fT4 (pmol/L) 30.16 (15.4; 53.4) 15 (13.18; 18.33) 0.112
TRAb (IU/I) 6.03 (2.56; 16.82) 2.68 (1.54; 3.56) 0.078
TPOAb (IU/mL) 122.5 (31.25; 281) 218 (154.5; 280.75) 0.538
TgAb (IU/mL) 71 (13; 325) 246 (84.5; 554.5) 0.204
CRP (mg/dL) 6.03 (2.56; 16.82) 2.68 (1.54; 3.56) 0.408
Creatinine (mg/mL) 0.57 (0.44; 0.73) 0.62 (0.57; 0.73) 0.267
ALT (U/I) 23.5 (17.25; 32) 24.5 (17.25; 28.75) 0.970
AST (U/I) 21.5 (16; 25) 22.5 (20.25; 26.25) 0.330
WBC (×103/μL) 6.46 ± 1.75 6.35 ± 2.3 0.878
RBC (×106/μL) 4.71 ± 0.4 4.76 ± 0.18 0.802
Hemoglobin (g/mL) 13.55 (12.63; 14.38) 14.1 (13.6; 14.38) 0.810
PLT (×103/μL) 4.71 ± 0.4 4.76 ± 0.18 0.802
Thyroid volume (cm3) 29.82 ± 21.83 19.35 ± 15.25 0.233
Intrathyroidal blood flow 1 (0; 2) 1 (0.25; 1.75) 0.707
Thyroid echogenicity 1 (1; 2) 1 (1; 1.75) 0.792
Presence of any thyroid nodule (% of patients) 36.73 16.67 0.653
Presence of multiple (≥3) thyroid nodules (% of patients) 18.37 0 0.574
Moderate-to-severe GO (% of patients) 14.81 66.67 0.012
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Medicine, Basic Medical Science, Biochemistry, Immunology, Clinical Medicine, other, Clinical Chemistry
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