Autoantibodies to Plasminogen and Their Role in Tumor Diseases

Goufman, Eugene; Yakovlev, V. N.; Tikhonova, N.B.; Айсина, Р.Б.; Yarygin, K. N.; Мухаметова, Л.И.; Gershkovich, K.B.; Gulin, D.A.

doi:10.1007/s10517-015-2792-1

Cited by 4 publications

(5 citation statements)

References 12 publications

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“…Here, we checked the relationship of anti-CD26 Abs with the other biomarkers, taking into account that antiplasminogen levels, in particular the IgG isotype, were recently related to some tumours [26]. The only hypothesis about the origin of anti-CD26 autoantibodies in healthy controls links again CD26/DPP4 with plasminogen as a consequence of an abnormal immune stimulation triggered by streptokinase (SK) released during streptococcal infections, a mechanism that also produces antiplasminogen [15,22].…”

Section: Discussionmentioning

confidence: 99%

“…If the autoantibodies were already present, the changes would still be detected earlier since it is not necessary to trigger the whole humoural mechanism. It may be relevant that high 8 Disease Markers antiplasminogen levels have been found in the tumours analysed (though no information was given for colorectal tumours [26]). Anti-CD26 might then participate in autoantibody signatures that would aid in the development of diagnostics, prognostics, and follow-up of therapeutics for cancer patients [27,28] and perhaps could identify subgroups of patients for precision medicine.…”

Section: Discussionmentioning

confidence: 99%

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CD26-Related Serum Biomarkers: sCD26 Protein, DPP4 Activity, and Anti-CD26 Isotype Levels in a Colorectal Cancer-Screening Context

et al. 2020

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Current screening trials are showing reduction in colorectal cancer incidence and mortality. However, participation rates are often low, and blood-based tests could complement existing screening strategies. CD26 protein (sCD26) and its dipeptidyl peptidase IV (DPP4) enzymatic activity in circulation have been proposed as biomarkers for colorectal cancer and other diseases. However, changes in sCD26 and DPP4 levels show complex degrees of correlation, and their physiological or pathophysiological role is unclear. The aim of this study was to analyse if anti-CD26 autoantibodies are related to sCD26 and DPP4 and to determine their relevance in a context of colorectal cancer screening for complementing the value of sCD26 and DPP4 as biomarkers. These biomarkers were measured in a large prospective cohort (n=497, except the anti-CD26 antibodies, evaluated in 125 samples) that included a subgroup of individuals that were positive for the faecal immunological occult blood test (FIT) (n=86) and underwent a colonoscopy (n=47). We confirmed for the first time higher DPP4 activity in men compared to women (Student’s t test, p=0.002), though this difference between sexes was not seen for serum sCD26 protein. These biomarkers correlated (R=0.246, p=0.003) only in women. Correlations were found between anti-CD26 isotypes but not with DPP4 activity or sCD26 concentration, except for a negative correlation only in men between anti-CD26 IgA isotype and sCD26 (R=−0.232, p=0.044), and an almost significant negative correlation between anti-CD26 IgG and sCD26 limited to FIT-positive men. Interestingly, patients with advanced adenomas displayed the most elevated mean levels of anti-CD26 IgA, IgM, and particularly IgG (Mann-Whitney U test, p=0.030) in comparison with the other FIT positives without adenomas, and these levels did not correlate with sCD26 or its DPP4 activity. Our preliminary results suggest that the combination of these measures using sex as confounder could perhaps be used as biomarkers for colorectal disease. It also suggests that events affecting the gut influence the levels of anti-CD26 antibodies, which show little or no effect in antigen clearance. These findings should be confirmed in a larger cohort of individuals with colonoscopy. The physiological origin of the sex differences observed should be further addressed.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

CD26-Related Serum Biomarkers: sCD26 Protein, DPP4 Activity, and Anti-CD26 Isotype Levels in a Colorectal Cancer-Screening Context

et al. 2020

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“…The levels of IgG, IgM, and IgA interacting with plasminogen were determined in blood plasma with sodium citrate by enzyme immunoassay on 96-well polystyrene plates (SPL Maxibinding, Korea), with human plasminogen immobilized at the bottom of the wells, as described previously [ 16 ]. Immunoglobulins bound to plasminogen were revealed by conjugates of specific mAbs against human IgG or IgM or IgA with horseradish peroxidase (Diateh-Em, Moscow, Russia).…”

Section: Methodsmentioning

confidence: 99%

“…In addition, decidual cells are producers of tissue plasminogen activator (tPA), being an important component of the fibrinolytic system, which is involved in tissue remodeling through activation of metalloproteinases and degradation of the extracellular matrix [ 15 ]. The regulation of hemostasis processes also could be influenced by autoantibodies to plasminogen, which are detected in tiny amounts in healthy women and in high concentrations in cases of some pathologies [ 16 ]. One of the main causes of vaginal bleeding during the first trimester of pregnancy is retrochorial hematoma, which could lead to complications and chorion detachment [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Hemostasis System and Plasminogen Activity in Retrochorial Hematoma in the First Trimester of Pregnancy

Tikhonova

Kuznetsova

et al. 2022

Biomedicines

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(1) Background: The components of the fibrinolytic system and its main component, plasminogen, play a key role in the first months of pregnancy. The effect of autoantibodies interacting with plasminogen in the formation of retrochorial hematoma is unknown. The aim of our study was to determine the role of plasminogen and IgA, IgM, and IgG, which bind to plasminogen, in retrochorial hematoma. (2) Methods: Prothrombin time (PT), thrombin time (TT), partial activated thromboplastin time (aPTT), soluble fibrin-monomer complex (SFMC), D-dimer, plasminogen activity (%Plg), plasminogen concentration (Plg), and the levels of IgG (IgG-Plg), IgM (IgM-Plg), IgA (IgA-Plg) interacting with plasminogen were determined in plasma samples of 57 women with normal pregnancy and 16 with retrochorial hematoma. (3) Results: %Plg in plasma samples from women with retrochorial hematoma was significantly lower than in plasma samples from women with normal pregnancy. The diagnostic significance of %Plg in the ROC analysis was AUC = 0.85. A direct correlation was found between aPTT and the level of autologous IgM interacting with plasminogen. (4) Conclusions: A decrease in the activity of plasminogen in the blood serum of women in the first trimester of pregnancy may indicate disturbances in the hemostasis system and the formation of retrochorial hematoma. According to the results of the study, it is possible to recommend the determination of plasminogen activity in the management of pregnant women in gynecological practice.

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“…Both PLG-H or PLG-L were immobilized on 96-well ELISA plates (SPL Maxibinding, Korea) as previously described [ 22 ]. Each well was filled with 100 μL of 5 µg/mL coating solution of PLG-H or PLG-L in 0.1 M sodium carbonate buffer (pH 9.6), then incubated overnight at 37 °C.…”

Section: Methodsmentioning

confidence: 99%

Proteolyzed Variant of IgG with Free C-Terminal Lysine as a Biomarker of Prostate Cancer

Lokshin

Михалева

Goufman

et al. 2021

Biology

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The differential diagnosis of prostate cancer is problematic due to the lack of markers with high diagnostic accuracy. We previously demonstrated the increased binding of IgG to human plasminogen (PLG) in plasma of patients with prostate cancer (PC) compared to healthy controls. Heavy and light chains of PLG (PLG-H and PLG-L) were immobilized on 96-well plates and the binding of IgG to PLG-H and PLG-L was analyzed in serum from 30 prostate cancer (PC) patients, 30 patients with benign prostatic hyperplasia (BPH) and 30 healthy controls using enzyme-linked immunosorbent assay (ELISA). Our results demonstrate that IgG from PC sera bind to PLG-H but not to PLG-L. This interaction occurred through the free IgG C-terminal lysine (Lys) that becomes exposed as a result of IgG conformational changes associated with proteolysis. Circulating levels of modified IgG with exposed C-terminal Lys (IgG-Lys) were significantly higher in PC patients than in healthy controls and in BPH. We used Receiver Operating Characteristic (ROC) analysis to calculate the sensitivity (SN) and specificity (SP) of circulating IgG-Lys for differentiating PC from BPH as 77% and 90%, respectively. The area under the curve (AUC) was 0.87. We demonstrated that the diagnostic accuracy of circulating levels of IgG-Lys is much higher than diagnostic accuracy of total PSA (tPSA).

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Autoantibodies to Plasminogen and Their Role in Tumor Diseases

Cited by 4 publications

References 12 publications

CD26-Related Serum Biomarkers: sCD26 Protein, DPP4 Activity, and Anti-CD26 Isotype Levels in a Colorectal Cancer-Screening Context

CD26-Related Serum Biomarkers: sCD26 Protein, DPP4 Activity, and Anti-CD26 Isotype Levels in a Colorectal Cancer-Screening Context

Hemostasis System and Plasminogen Activity in Retrochorial Hematoma in the First Trimester of Pregnancy

Proteolyzed Variant of IgG with Free C-Terminal Lysine as a Biomarker of Prostate Cancer

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