Introduction

Type 2 glycoprotein (GP2) is a quantitatively predominant membrane protein of excretory granules of pancreatic acinar cells. In a number of studies, it has been demonstrated that this protein is the main antigen for pancreatic antibodies associated with Crohn's disease (CD). Zonulin – a protein that can reversibly increase the permeability of the intestinal wall by changing the structure of tight junctions of the lateral surfaces of intestinal epithelial cells. The determination of fecal zonulin is used for noninvasive assessment of increased intestinal permeability. Normal values of fecal zonulin (≤ 110 ng/ml) indicate the absence of damage to the villous surface of the intestinal mucosa and normal density of intercellular contacts.

Aims & Methods

The aim of the study was to establish the dependence of the level of type 2 glycoprotein on the level of fecal zonulin (FZ) in the feces of CD patients with exacerbation of the disease.
Material and methods. 122 patients with CD in the form of ilekolitis with exacerbation of the disease (Me age — 32 years) were examined. FZ was evaluated by ELISA (IDK ® Zonulin ELISA Kit, Immunodiagnostik AG, Germany) in ng/ml. Reference values: < 83.15 ng/ml is a variant of the norm, 83.15-110 ng/ml is an elevated level, 110 ng/ml is a high level.
The level of IgG and IgA to GP2 (antibodies to glycoprotein) antigen of pancreatic centroacinar cells (Anti-GP2, IgG, IgA) was determined by ELISA. Reference values: IgG GP-2 less than 10 units/ml, Ig and GP-2 less than 5 units/ml – positive values.

Results

In the stool samples of CD patients during the period of exacerbation in 92 (75,4%) patients, an increase in FZ was detected, the average value was 333.4 ±16.9 ng/ml. In the blood samples of 81 (66,4%) patients with CD during the period of exacerbation, an increase in Ig A GP-2 was detected, the average value was 43.4±6.9 units/ml. In the blood samples of 107 CD patients during the period of exacerbation, an increase in Ig G GP-2 was detected, the average value was 17.1 ± 1.3 units/ml. There is a high correlation force between the concentration of FZ and the concentration of Ig A GP-2 (r-0.760) (p=0.010). There is a moderate correlation force (r-0.490) (p=0.023) between the concentration of FZ and the concentration of Ig G GP-2.

Conclusion

An increase in the concentration of FZ in the feces of CD patients during exacerbation significantly correlates with an increase in the concentration of Ig A GP-2 and Ig G GP-2.

Introduction

Type 2 Glycoprotein (GP2) is a quantitatively predominant membrane protein of excretory granules of pancreatic acinar cells. In a number of studies, it has been demonstrated that this protein is the main antigen for pancreatic antibodies associated with Crohn's disease Zonulin – a protein that can reversibly increase the permeability of the intestinal wall by changing the structure of tight junctions of the lateral surfaces of intestinal epithelial cells. The determination of fecal zonulin is used for noninvasive assessment of increased intestinal permeability. Normal values of fecal zonulin (≤ 110 ng/ml) indicate the absence of damage to the villous surface of the intestinal mucosa and normal density of intercellular contacts

Aims & Methods

The aim of the study was to establish the dependence of the level of type 2 glycoprotein on the level of fecal zonulin (FZ) in the feces of CD patients with exacerbation of the disease.
Material and methods. 217 patients with CD in remission of the disease (Ме age — 38 years) were examined. FZ was evaluated by ELISA (IDK ® Zonulin ELISA Kit, Immunodiagnostik AG, Germany) in ng/ml. Reference values: < 83.15 ng/ml - a variant of the norm, 83.15-110 ng/ml - an elevated level, 110 ng/ml - a high level.
The level of IgG and IgA to GP2 (antibodies to glycoprotein) antigen of pancreatic centroacinar cells (Anti-GP2, IgG, IgA) was determined by ELISA. Reference values: IgG GP-2 less than 10 units/ml, Ig And GP-2 less than 5 units/ml – positive values.

Results

In the stool samples of CD patients during remission in 76 (35%) patients, an increase in the FZ was detected, the average value was 235.4±11.6 ng/ml. In the blood samples of 59 (27.2%) CD patients during remission, an increase in Ig A GP-2 was detected, the average value was 24.4±1.9 units/ml. In the blood samples of 137 CD patients during remission, an increase in Ig G GP-2 was detected, the average value was 19.7±1.1 units/ml. There is no correlation between the concentration of FZ and the concentration of Ig A GP-2 (r-0.260) (p>0.05). There is a moderate correlation force (r-0.310) (p=0.033) between the concentration of FZ and the concentration of Ig G GP-2.

Conclusion

There is no correlation between the concentration of FZ in the feces of CD patients during remission with the concentration of Ig A GP-2 and Ig G GP-2 in the blood serum of patients.

Introduction

Risankizumab (RZB) is a P19 subunit blocking anti-IL-23 agent that has been shown to be effective in CD in a recent Phase 3 trial (Ferrante et al., Lancet 2022). Compassionate use has been possible since June 2022. The aim of this work was to investigate whether RZB levels correlate with biomarker-based remission.

Aims & Methods

Any CD patient on RZB (compassionate use or open-label phase 3 study) was eligible for the study. All patients were treated with a regimen of RZB (600mg/IV S0, S4 and S8) followed by 360 mg/sc every 8 weeks starting at S12. Patients who had received other regimens were excluded. Before each infusion or SC injection, fecal calprotectin, CRP and RZB levels were measured using an ELISA test. The assays were blinded to clinical and biomarker datas. Clinical remission was defined as CDAI score < 150 Conversly, clinical activity was definied by a CDAI score > 220. Biomarker remission was defined as fecal calprotectin levels below 250 µg/ml and CRP < 5 mg/l.

Results

26 patients (mean age: 42 years, sex ratio M/F: 1.3) with 97 maintenance RZB samples (360mg/sc every 8S) were eligible. In 37 cases, RZB samples were taken while biomarkers were in remission. During, maintenance, mean RZB levels were significantly higher in cases of clinical remission than in the absence of clinical remission (22.5 versus 6.1 µg/ml; p<0.0001)(Figure 1). Mean RZB levels were similar between patients in clinical remission and patients in clinical and biomarker remissions (22.5 versus 19.6 µg/ml; p<0.0001). The higher RZB trough level quartiles tended to be associated with greater rates of clinical response [p = 0.001]. Clinical remission rates were 4% if RZB trough levels were ≤4.9 μg/mL [quartile 1] and 88% if RZB trough levels were >19.6 μg/mL [quartile 4] (Figure 2).

Conclusion

RZB levels are significantly higher in patients with clinical remission in CD. Trough concentration of RZB above 10.6µg/mL should be recommended in clinical practice.

References

Ferrantet et al., Lancet 2022