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Suppressed immune profile in children with type 1 diabetes in combination with celiac disease

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(1)

Andrea Tompa

1, 2

, Karin Åkesson

3

, Sandra Karlsson

2

, Maria Faresjö

2 1 Department of Laboratory Medicine, Region Jönköping County, Sweden

2 Department of Natural Science and Biomedicine, School of Health and Welfare, Jönköping University, Sweden 3 Department of Pediatrics, Region Jönköping County, Sweden

Hierarchical cluster analysis was used to identify similarities/

differences in immune marker profiles between children with double diagnosis and children with single diagnosis and control children.

Cytokines, chemokines, acute phase proteins (APP), adipocytokines and matrix metalloproteinases (MMP) are involved in different pathophysiological processes of inflammatory character. Children diagnosed with T1D and CD show a diminished T helper (Th) 1-like profile and recent studies suggest also a dysregulated Th17 response. The role of the different immune markers and the peripheral immunoregulatory milieu in children diagnosed with T1D in combination with CD is not fully understood and is not well studied.

2

The purpose of the present study was therefore to acquire more knowledge and to gain deeper understanding on peripheral immunoregulatory milieu in children with T1D and/or CD.

Suppressed immune profile in children with type 1 diabetes in

combination with celiac disease

BACKGROUND and AIM

BACKGROUND and AIM

MATERIALS and METHODS

MATERIALS and METHODS

Our observations indicate decreased serum levels of IL-22, MIP-1α, MCP-1, PCT, visfatin and MMP-2 in children diagnosed with type 1 diabetes (T1D) in combination with celiac disease (CD).

These results indicate a suppressed immune profile including Th17 cytokines, chemokines, acute phase proteins, adipocytokines and matrix metalloproteinase immune markers in children diagnosed with both T1D and CD.

Functional studies of the involved antigen specific immune cells (CD4+Treg, CD8+Treg, NK-cells and dendritic cells) could contribute to elucidate the heterogeneous immunological processes in children with more than one autoimmune disease.

CONCLUSION

RESULTS

RESULTS

Acknowledgment: This work was funded with grants from The Academy of Health and Care (Futurum)andDepartment of Laboratory Medicine

Region Jönköping County, Jönköping, Sweden.

Contact: Andrea Tompa, MSc, PhD student, School of Health and Welfare, Jönköping University, Sweden, E-mail: Andrea.Tompa@ju.se

T1D+CD 6% CD 19% T1D 50% Control 25% Cluster B T1D+CD 0% CD 28% T1D 29% Control 43% Cluster C T1D+CD 18% CD 15% T1D 26% Control 41% Whole group

The largest cluster (A), included 75% of the participants (n=75) and the diagnose distribution in the cluster were very similar to the distribution in the whole study cohort.

Cluster B included 15.5% of participants (n =18), and cluster C included the remaining 6.5% (n =7).

T1D (n=27)

Matrix Metalloproteinases

• MMP-1, MMP-2, MMP-3

Th-cytokines

• Th1 - IFN-γ

• Th2 - IL-5, IL-9, IL-10, IL-13 • Th17 - IL-17A, IL-22, IL-25, IL-33

APC cyto/chemokines

• IL-1β, IL-6, IL-15, TNF-α, IL-8, MCP-1, MIP-1α, MIP-1β, G-CSF APP • PTC, Ferritin, tPA, Fibrinogen, SAA Adipocytokines • Visfatin, Resistin

The major finding of this study showed, observed within cluster A, that children with double diagnosis had lower serum levels of IL-22, MCP-1 and PCT compared to children with T1D; and lower serum levels of MIP-1α and MMP-2 compared to control children observed in the main cluster. Most of these observations were also seen in the whole cohort.

In the whole cohort we have also seen decreased visfatin level in double diagnosis group compared to children with T1D.

T1D+CD 22% CD 13% T1D 20% Control 45% Cluster A

Table 1. Differences in immune marker levels in serum in children with double diagnosis (T1D+CD), children with T1D or CD and control children presented for the whole group and for Cluster A.

CD (n=16)

T1D+CD (n=18) Control (n=42)

/ Significant lower/higher immune marker level 1= in comparison with Control; 2= in comparison with T1D; 3 = in comparison with CD.A=Cluster A

References

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