Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Jan 30:2021:3676942.
doi: 10.1155/2021/3676942. eCollection 2021.

Aberrant Expression of a Proliferation-Inducing Ligand Underlies Autoimmune Mechanisms in Immune Thrombocytopenia

Affiliations

Aberrant Expression of a Proliferation-Inducing Ligand Underlies Autoimmune Mechanisms in Immune Thrombocytopenia

Y F Hao et al. J Immunol Res. .

Abstract

Purpose: To study the relationship between surface membrane-bound APRIL and ITP.

Methods: The peripheral blood of all subjects, 50 patients diagnosed with ITP and 25 healthy controls, was collected. Flow cytometry was used to detect the expression of membrane-bound APRIL on immune cells and platelets. ELISA was used to detect the content of soluble APRIL in plasma.

Results: Membrane-bound APRIL was only expressed on the surface of platelets in both ITP patients and controls. APRIL expression on the platelet surface was significantly lower in newly diagnosed (P < 0.001) and chronic (P < 0.001) ITP patients than in controls. Platelet surface APRIL level was significantly enhanced in patients with complete remission after treatment (P = 0.02) but not in those with no response after treatment. Platelet surface APRIL level in ITP patients was negatively correlated with serum APRIL level (r = -0.09765, P = 0.0424).

Conclusions: Platelet surface APRIL may play a key immunoregulative role. Platelet surface APRIL is likely to be one source of the excessive serum APRIL in ITP patients. The effectiveness of treatment may be measured by determining the platelet surface APRIL levels in ITP patients.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
Representative histograms show surface APRIL and isoform staining of platelets (a), B cells (b), T cells (c), and monocytes (d).
Figure 2
Figure 2
Decreased surface expression of APRIL on platelets in ITP patients. (a) Platelets from healthy donors and ITP patients were isolated by flow cytometry based on surface expression of APRIL. Forward and side light scatter (FSC and SSC, respectively) and intact cell gates (left panels) were used for platelet gating (right panels). (b) Representative histograms show surface APRIL and isotype labeling in gated platelets. (c) MFI of surface APRIL expression in gated platelets from healthy donors and ITP patients. (d) Spearman's test showed that APRIL expression in ITP patients (n = 50) was highly correlated with platelet count. (e, f) Differences in APRIL MFI in ITP patients in complete remission (n = 10) (e) and nonresponders (n = 8) (f) before and after treatment.
Figure 3
Figure 3
Plasma APRIL levels in ITP patients. (a) Plasma APRIL levels were higher in chronic and newly diagnosed ITP patients than in normal controls (n = 25 per group), with no significant difference between the two patient groups. (b) APRIL concentration was negatively correlated with platelet count in ITP patients (n = 50). (c) Correlation between platelet surface APRIL and serum APRIL levels in ITP patients. (d–f) Differences in Plasma APRIL levels before and after treatment in the chronic ITP patient group (n = 25) (d) in the complete remission group (n = 10) (e) and the nonresponse group (n = 8) (f).

References

    1. Ballem P. J., Segal G. M., Stratton J. R., Gernsheimer T., Adamson J. W., Slichter S. J. Mechanisms of thrombocytopenia in chronic autoimmune thrombocytopenic purpura. Evidence of both impaired platelet production and increased platelet clearance. The Journal of Clinical Investigation. 1987;80(1):33–40. doi: 10.1172/JCI113060. - DOI - PMC - PubMed
    1. Zufferey A., Kapur R., Semple J. W. Pathogenesis and therapeutic mechanisms in immune thrombocytopenia (ITP) Journal of Clinical Medicine. 2017;6(2):p. 16. doi: 10.3390/jcm6020016. - DOI - PMC - PubMed
    1. Chen J. F., Yang L. H., Chang L. X., Feng J. J., Liu J. Q. The clinical significance of circulating B cells secreting anti-glycoprotein IIb/IIIa antibody and platelet glycoprotein IIb/IIIa in patients with primary immune thrombocytopenia. Hematology. 2013;17(5):283–290. doi: 10.1179/1607845412Y.0000000014. - DOI - PubMed
    1. Fogarty P. F. ITP: tolerance lost. Blood. 2011;118(24):6232–6234. doi: 10.1182/blood-2011-10-383893. - DOI - PubMed
    1. Matthes T., Dunand-Sauthier I., Santiago-Raber M. L., et al. Production of the plasma-cell survival factor a proliferation-inducing ligand (APRIL) peaks in myeloid precursor cells from human bone marrow. Blood. 2011;118(7):1838–1844. doi: 10.1182/blood-2011-01-332940. - DOI - PubMed

MeSH terms

Substances

LinkOut - more resources